Alessandro Cataliotti

• Pioppi, Leonardo; Parvan, Reza; Cardinali, Martina Alunni; Silva, Gustavo Jose Justo Da; Bracco, Brenda & Stefani, Sara [Vis alle 8 forfattere av denne artikkelen] (2026). Label-Free Detection of Molecular Signatures in Heart Failure with Preserved Ejection Fraction Using Raman Micro-Spectroscopy. International Journal of Molecular Sciences. ISSN 1661-6596. 27(5). doi: 10.3390/ijms27052161. Fulltekst i vitenarkiv
• Parvan, Reza; Becker, Victoria; Milad, Hosseinpour,; Yousef, Moradi,; Louch, William Edward & Cataliotti, Alessandro [Vis alle 9 forfattere av denne artikkelen] (2025). Prognostic and predictive microRNA panels for heart failure patients with reduced or preserved ejection fraction: a meta-analysis of Kaplan–Meier-based individual patient data. BMC Medicine. 23. doi: 10.1186/s12916-025-04238-0. Fulltekst i vitenarkiv Vis sammendrag

  Cardiac troponins and natriuretic peptides are benchmark biomarkers for heart failure (HF) with reduced ejection fraction (HFrEF) but have limited prognostic performance for HF patients with preserved ejection fraction (HFpEF). Non-coding RNA-based biomarkers represent an innovative approach to risk-stratify patients and might address the unmet need for minimally invasive prognostic and predictive tools for HF development and HF-related outcomes. Our aim is to investigate the prognostic performance and risk stratification potential of circulating panels of microRNAs (miRNAs) in HFrEF and HFpEF. A systematic search on PubMed, Web of Science, and Scopus databases was performed for studies reporting miRNAs as prognostic biomarkers in HF patients. A total of 22 studies pooling 5736 participants were included for quantitative analysis. KM-based individual patient data (IPD) analysis was performed in 12 studies (5064 participants). KM-based IPD analysis in HFrEF allowed the identification of a panel of four miRNAs (miR-27a-3p, miR-129-5p, miR-145-5p, and miR-590-3p) predicting the risk of all-cause death with hazard ratio (HR) 4.26 [2.68–6.76]. MiR-122-5p and miR-423-5p predicted cardiovascular death of HFrEF patients (HR 3.61 [2.67–4.87]). In HFpEF, miR-19a-3p predicted all-cause death of HFpEF patients with HR 2.23 [1.16–4.27]. Moreover, a panel of eight miRNAs (miR-17-5p, miR-20a-5p, miR-21, miR-23, miR-27, miR-106b-5p, miR-210, and miR-221) showed significant association with HF incidence (HR 2.14 [1.81–2.53]). A comprehensive meta-analysis of KM-based IPD enabled the identification of unique miRNA panels predicting the incidence and severity of HFrEF and HFpEF, supporting the clinical usefulness of miRNA profiling for tailored healthcare and risk stratification in HF patients. Nonetheless, more rigorously designed longitudinal studies are needed to validate the clinical application of miRNAs as prognostic and predictive biomarkers.

• Bergo, Kaja Knudsen; Nordén, Einar Sjaastad; Bendiksen, Bård Andre; Espe, Emil Knut Stenersen; Mcginley, Gary George & Hauge-Iversen, Ida Marie [Vis alle 12 forfattere av denne artikkelen] (2025). Sacubitril/valsartan preserves kidney function in rats with cardiorenal syndrome after myocardial infarction. PLOS ONE. 20(10). doi: 10.1371/journal.pone.0335214. Fulltekst i vitenarkiv Vis sammendrag

  Renal dysfunction in heart failure increases mortality, limits treatment options and blunts responses to therapy. Angiotensin receptor-blocker and neprilysin inhibitors (ARNI) may preserve renal function by modulating both the renin-angiotensin-aldosterone system and the natriuretic peptide system. We investigated the renal effects of the ARNI Sacubitril/valsartan (Sac/Val) in rats with systolic dysfunction secondary to myocardial infarction. Male Sprague-Dawley rats underwent surgical MI induction and were randomized to six weeks of treatment with vehicle, valsartan or Sac/Val, and compared to sham operated animals. Renal function was evaluated by creatinine clearance, mean arterial pressure (MAP) by tail-cuff measurements, and cardiac function by magnetic resonance imaging and echocardiography. Vehicle treated animals developed cardiorenal syndrome, with impaired cardiac systolic function and mild renal dysfunction. Both valsartan and Sac/Val preserved renal function compared to vehicle (creatinine clearance mL/min [median with interquartile range]; sham 5.4 [4.8–6.0], vehicle 4.5 [4.1–5.1], valsartan 5.1 [5.1–5.5], Sac/Val 5.1 [5.0–5.6]; vehicle vs valsartan p = 0.034 and vehicle vs Sac/Val p = 0.044). MAP was reduced by both treatments compared to sham and vehicle groups (MAP mmHg ; sham 131 [116–138], vehicle 123 [115–132], valsartan 108 [99–112], Sac/Val 111 [99–119]; sham vs valsartan p < 0.001 and sham vs Sac/Val p = 0.003, vehicle vs valsartan p = 0.006 and vehicle vs Sac/Val p = 0.041). Only Sac/Val reduced left atrial dilatation (diameter mm ; sham 4.1 [3.7–4.4], vehicle 4.6 [3.8–5.6], valsartan 4.6 [4.1–5.5], Sac/Val 3.9 [3.6–4.5]; vehicle vs Sac/Val p = 0.047, valsartan vs Sac/Val p = 0.017) despite no improvement in systolic function in either treatment group. Sac/Val initiated in the acute post-MI phase preserved renal function to the same extent as valsartan alone and uniquely reduced left atrial dilatation, suggesting additional benefits beyond renoprotection in the setting of persistent systolic dysfunction.

• Parvan, Reza; Rolim, Natale Pinheiro Lage; Gevaert, Andreas B.; Cataliotti, Alessandro; Craenenbroeck, Emeline M. van & Adams, Volker [Vis alle 8 forfattere av denne artikkelen] (2025). Multi-microRNA diagnostic panel for heart failure with preserved ejection fraction in preclinical and clinical settings. ESC Heart Failure. 12(4), s. 3028–3041. doi: 10.1002/ehf2.15324. Fulltekst i vitenarkiv Vis sammendrag

  Aims Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome accounting for half of heart failure cases. Although natriuretic peptides are the most accepted and extensively used biomarkers for heart failure, their diagnostic accuracy for HFpEF remains debatable. Here, we aimed to identify a panel of circulating microRNAs (miRNAs) as potential novel biomarkers for diagnosis of HFpEF in a preclinical model, subsequently validated in human HFpEF patients. Methods and results In a female hypertension-induced HFpEF model [Dahl/Salt Sensitive (DSS) rats], circulating miRNA levels were screened in the plasma via real-time quantitative polymerase chain reaction. DSS rats exhibited HFpEF features as indicated by diastolic dysfunction and adverse cardiac remodelling when fed a high-salt (8%) diet (n = 11) compared with a low-salt (0.3%) diet (n = 15). A panel of four circulating miRNAs (rno-let-7b-5p, rno-let-7e-5p, rno-miR-21-5p and rno-miR-140-3p) were found significantly altered in the DSS plasma. Clinical performance of miRNA expression analysis was assessed in publicly available datasets of human heart failure patients, including assessment of discrimination of different categories of heart failure [GSE53437; control = 30, heart failure with reduced ejection fraction (HFrEF) = 41, HFpEF = 19] and gender differences (GSE104150; female = 6, male = 10). The miRNA panel significantly discriminated HFpEF patients from healthy individuals and HFrEF patients. We also found significant downregulation of let-7b-5p and miR-21-5p in females compared with males, regardless of health status. Conclusions A panel of four circulating miRNAs was differently expressed in female HFpEF rats and significantly discriminated HFpEF patients from healthy individuals and HFrEF patients. This cross-species and bench-to-bedside approach demonstrates the potential of miRNA-based panels for HFpEF diagnosis.

• Nordén, Einar Sjaastad; Bendiksen, Bård Andre; Bergo, Kaja Knudsen; Espe, Emil Knut Stenersen; Mcginley, Gary George & Hasic, Almira [Vis alle 17 forfattere av denne artikkelen] (2024). Sacubitril/valsartan preserves regional cardiac function following myocardial infarction in rats. ESC Heart Failure. doi: 10.1002/ehf2.15145. Fulltekst i vitenarkiv Vis sammendrag

  Aims Sacubitril/valsartan (Sac/Val) is used for treatment of heart failure. The effect of Sac/Val on regional dysfunction following myocardial infarction (MI) remains uncertain. This study aimed at understanding the effects of Sac/Val on regional function after MI. Methods and results MI or sham surgery was performed in Sprague–Dawley rats. Animals were randomized to treatment with Sac/Val, valsartan (Val) or vehicle (Veh). Magnetic resonance imaging was used to acquire left ventricular volumes and strain. Left ventricular tissue was obtained for wesern blotting, PCR and Masson's trichrome staining. Isolated cardiac fibroblasts were cultured with Veh, atrial natriuretic peptide (ANP), adrenomedullin (ADM) and sacubitrilat, and collagen expression assessed with droplet digital PCR. Results Sac/Val reduced ventricular end-diastolic volume by 18% compared with Veh, and preserved circumferential systolic strain in the zone proximal to infarction compared with sham after 42 days of treatment (peak strain ± SEM: sham: −0.19 ± 0.01%; Sac/Val: −0.14 ± 0.02%; Val: −0.10 ± 0.02%; Veh: −0.10 ± 0.02%). Masson's trichrome staining demonstrated lower fibrotic deposition in the intermediate zone with Sac/Val treatment than Veh (sham: 2.29 ± 0.17%; Sac/Val: 2.31 ± 0.27%; Val: 3.22 ± 0.60%; Veh: 4.14 ± 0.48%). The amounts of the pro-apoptotic caspase 3 cleavage fragments p19/17 were 89% higher in Val than sham, with Sac/Val showing no significant increase compared with sham. Collagen expression in human fibroblast culture was lower in cells co-treated with sacubitrilat and ANP, an effect not observed with sacubitrilat/ADM co-treatment. Conclusions Sac/Val preserves in vivo myocardial function in the region most proximal to MI in rats and reduces left ventricular dilatation. These effects may be related to a reduction in both fibrosis and pro-apoptotic signalling.

• Andresen, Henriette; Pérez-Ternero, Cristina; Robinson, Jerid; Dickey, Deborah M.; Hobbs, Adrian J. & Potter, Lincoln R. [Vis alle 9 forfattere av denne artikkelen] (2023). Novel enhancers of guanylyl cyclase-A activity acting via allosteric modulation. British Journal of Pharmacology. ISSN 0007-1188. doi: 10.1111/bph.16203. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background and Purpose Guanylyl cyclase‐A (GC‐A), activated by endogenous atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), plays an important role in the regulation of cardiovascular and renal homeostasis and is an attractive drug target. Even though small molecule modulators allow oral administration and longer half‐life, drug targeting of GC‐A has so far been limited to peptides. Thus, in this study we aimed to develop small molecular activators of GC‐A. Experimental Approach Hits were identified through high‐throughput screening and optimized by in silico design. Cyclic GMP was measured in QBIHEK293A cells expressing GC‐A, GC‐B or chimerae of the two receptors using AlphaScreen technology. Binding assays were performed in membrane preparations or whole cells using 125 I‐ANP. Vasorelaxation was measured in aortic rings isolated from Wistar rats. Key Results We have identified small molecular allosteric enhancers of GC‐A, which enhanced ANP or BNP effects in cellular systems and ANP‐induced vasorelaxation in rat aortic rings. The mechanism of action appears novel and not mediated through previously described allosteric binding sites. In addition, the selectivity and activity depend on a single amino acid residue that differs between the two similar receptors GC‐A and GC‐B. Conclusion and Implications We describe a novel allosteric binding site on GC‐A, which can be targeted by small molecules to enhance ANP and BNP effects. These compounds will be valuable tools in further development and proof‐of‐concept of GC‐A enhancement for the potential use in cardiovascular therapy.

• Pioppi, Leonardo; Tombolesi, Niki; Parvan, Reza; Silva, Gustavo Jose Justo; Altara, Raffaele & Paolantoni, Marco [Vis alle 9 forfattere av denne artikkelen] (2023). FTIR Analysis of Renal Tissue for the Assessment of Hypertensive Organ Damage and proANP<inf>31–67</inf> Treatment. International Journal of Molecular Sciences. ISSN 1661-6596. 24(6). doi: 10.3390/ijms24065196. Fulltekst i vitenarkiv Vis sammendrag

  The kidneys are one of the main end organs targeted by hypertensive disease. Although the central role of the kidneys in the regulation of high blood pressure has been long recognized, the detailed mechanisms behind the pathophysiology of renal damage in hypertension remain a matter of investigation. Early renal biochemical alterations due to salt-induced hypertension in Dahl/salt-sensitive rats were monitored by Fourier-Transform Infrared (FTIR) micro-imaging. Furthermore, FTIR was used to investigate the effects of proANP31–67, a linear fragment of pro-atrial natriuretic peptide, on the renal tissue of hypertensive rats. Different hypertension-induced alterations were detected in the renal parenchyma and blood vessels by the combination of FTIR imaging and principal component analysis on specific spectral regions. Changes in amino acids and protein contents observed in renal blood vessels were independent of altered lipid, carbohydrate, and glycoprotein contents in the renal parenchyma. FTIR micro-imaging was found to be a reliable tool for monitoring the remarkable heterogeneity of kidney tissue and its hypertension-induced alterations. In addition, FTIR detected a significant reduction in these hypertension-induced alterations in the kidneys of proANP31–67-treated rats, further indicating the high sensitivity of this cutting-edge imaging modality and the beneficial effects of this novel medication on the kidneys.

• Espino-Gonzalez, Ever; Tickle, Peter G.; Altara, Raffaele; Gallagher, Harrison; Cheng, Chew W. & Engman, Viktor [Vis alle 20 forfattere av denne artikkelen] (2023). Caloric Restriction Rejuvenates Skeletal Muscle Growth in Heart Failure With Preserved Ejection Fraction. JACC: Basic to Translational Science. ISSN 2452-302X. doi: 10.1016/j.jacbts.2023.09.014. Fulltekst i vitenarkiv Vis sammendrag

  Heart failure with preserved ejection fraction (HFpEF) is a major clinical problem, with limited treatments. HFpEF is characterized by a distinct, but poorly understood, skeletal muscle pathology, which could offer an alternative therapeutic target. In a rat model, we identified impaired myonuclear accretion as a mechanism for low myofiber growth in HFpEF following resistance exercise. Acute caloric restriction rescued skeletal muscle pathology in HFpEF, whereas cardiac therapies had no effect. Mechanisms regulating myonuclear accretion were dysregulated in patients with HFpEF. Overall, these findings may have widespread implications in HFpEF, indicating combined dietary with exercise interventions as a beneficial approach to overcome skeletal muscle pathology.

• Pioppi, Leonardo; Parvan, Reza; Samrend, Alan; Silva, Gustavo Jose Justo; Paolantoni, Marco & Sassi, Paola [Vis alle 7 forfattere av denne artikkelen] (2023). Vibrational spectroscopy identifies myocardial chemical modifications in heart failure with preserved ejection fraction. Journal of Translational Medicine. 21. doi: 10.1186/s12967-023-04465-0. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background Vibrational spectroscopy can be a valuable tool to monitor the markers of cardiovascular diseases. In the present work, we explored the vibrational spectroscopy characteristics of the cardiac tissue in an experimental model of heart failure with preserved ejection fraction (HFpEF). The goal was to detect early cardiac chemical modifications associated with the development of HFpEF. Methods We used the Fourier-transform infrared (FTIR) and Raman micro-spectroscopic techniques to provide complementary and objective tools for the histological assessment of heart tissues from an animal model of HFpEF. A new sampling technique was adopted (tissue print on a CaF 2 disk) to characterize the extracellular matrix. Results Several spectroscopic markers (lipids, carbohydrates, and glutamate bands) were recognized in the cardiac ventricles due to the comorbidities associated with the pathology, such as obesity and diabetes. Besides, abnormal collagen cross-linking and a decrease in tryptophan content were observed and related to the stiffening of ventricles and to the inflammatory state which is a favourable condition for HFpEF. Conclusions By the analyses of tissues and tissue prints, FTIR and Raman techniques were shown to be highly sensitive and selective in detecting changes in the chemistry of the heart in experimental HFpEF and its related comorbidities. Vibrational spectroscopy is a new approach that can identify novel biomarkers for early detection of HFpEF.

• Parvan, Reza; Hosseinpour, Milad; Moradi, Yousef; Devaux, Yvan; Cataliotti, Alessandro & Silva, Gustavo Jose Justo Da (2022). Diagnostic performance of microRNAs in the detection of heart failure with reduced or preserved ejection fraction: a systematic review and meta-analysis. European Journal of Heart Failure. ISSN 1388-9842. 24. doi: 10.1002/ejhf.2700. Fulltekst i vitenarkiv Vis sammendrag

  Aim Chronic heart failure (CHF) can be classified as heart failure with preserved ejection fraction (HFpEF) or with reduced ejection fraction (HFrEF). Currently, there is an unmet need for a minimally invasive diagnostic tool for different forms of CHF. We aimed to investigate the diagnostic potential of circulating microRNAs (miRNAs) for the detection of different CHF forms via a systematic review and meta-analysis approach. Methods and results Comprehensive search on Medline, Web of Science, Scopus, and EMBASE identified 45 relevant studies which were used for qualitative assessment. Out of these, 29 studies were used for qualitative and quantitative assessment and allowed to identify a miRNA panel able to detect HFrEF and HFpEF with areas under the curve (AUC) of 0.86 and 0.79, respectively. A panel of eight miRNAs (hsa-miR-18b-3p, hsa-miR-21-5p, hsa-miR-22-3p, hsa-miR-92b-3p, hsa-miR-129-5p, hsa-miR-320a-5p, hsa-miR-423-5p, and hsa-miR-675-5p) detected HFrEF cases with a sensitivity of 0.85, specificity of 0.88 and AUC of 0.91. A panel of seven miRNAs (hsa-miR-19b-3p, hsa-miR-30c-5p, hsa-miR-206, hsa-miR-221-3p, hsa-miR-328-5p, hsa-miR-375-3p, and hsa-miR-424-5p) identified HFpEF cases with a sensitivity of 0.82 and a specificity of 0.61. Conclusions Although conventional biomarkers (N-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide) presented a better performance in detecting CHF patients, the results presented here pointed towards specific miRNA panels with potential additive values to circulating natriuretic peptides in the diagnosis of different classes of CHF. Equally important, miRNAs alone showed a reasonable capacity for ‘ruling out’ patients with HFrEF or HFpEF. Additional studies with large populations are required to confirm the diagnostic potential of miRNAs for sub-classes of CHF.

• Tombolesi, Niki; Altara, Raffaele; Silva, Gustavo Jose Justo; Tannous, Cynthia; Zouein, Fouad A. & Stensløkken, Kåre-Olav [Vis alle 11 forfattere av denne artikkelen] (2022). Early cardiac-chamber-specific fingerprints in heart failure with preserved ejection fraction detected by FTIR and Raman spectroscopic techniques. Scientific Reports. 12(1). doi: 10.1038/s41598-022-07390-2. Fulltekst i vitenarkiv Vis sammendrag

  Abstract The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is a matter of investigation and its diagnosis remains challenging. Although the mechanisms that are responsible for the development of HFpEF are not fully understood, it is well known that nearly 80% of patients with HFpEF have concomitant hypertension. We investigated whether early biochemical alterations were detectable during HFpEF progression in salt-induced hypertensive rats, using Fourier-transformed infrared (FTIR) and Raman spectroscopic techniques as a new diagnostic approach. Greater protein content and, specifically, greater collagen deposition were observed in the left atrium and right ventricle of hypertensive rats, together with altered metabolism of myocytes. Additionally, Raman spectra indicated a conformational change, or different degree of phosphorylation/methylation, in tyrosine-rich proteins. A correlation was found between tyrosine content and cardiac fibrosis of both right and left ventricles. Microcalcifications were detected in the left and right atria of control animals, with a progressive augmentation from six to 22 weeks. A further increase occurred in the left ventricle and right atrium of 22-week salt-fed animals, and a positive correlation was shown between the mineral deposits and the cardiac size of the left ventricle. Overall, FTIR and Raman techniques proved to be sensitive to early biochemical changes in HFpEF and preceded clinical humoral and imaging markers.

• Silva, Gustavo Jose Justo; Altara, Raffaele; Booz, George W. & Cataliotti, Alessandro (2021). Atrial natriuretic peptide 31-67: A novel therapeutic factor for cardiovascular diseases. Frontiers in Physiology. 12(691407). doi: 10.3389/fphys.2021.691407. Fulltekst i vitenarkiv Vis sammendrag

  The characterization of the cardiac hormone atrial natriuretic peptide (ANP 9 9 – 1 26 ), synthesized and secreted predominantly by atrial myocytes under stimulation by mechanical stretch, has established the heart as an endocrine organ with potent natriuretic, diuretic, and vasodilating actions. Three additional distinct polypeptides resulting from proteolytic cleavage of proANP have been identified in the circulation in humans. The mid-sequence proANP fragment 31–67 (also known as proANP 3 1 – 6 7 ) has unique potent and prolonged diuretic and natriuretic properties. In this review, we report the main effects of this circulating hormone in different tissues and organs, and its mechanisms of actions. We further highlight recent evidence on the cardiorenal protective actions of chronic supplementation of synthetic proANP 3 1 – 6 7 in preclinical models of cardiorenal disease. Finally, we evaluate the use of proANP 3 1 – 6 7 as a new therapeutic strategy to repair end-organ damage secondary to hypertension, diabetes mellitus, renal diseases, obesity, heart failure, and other morbidities that can lead to impaired cardiac function and structure.

• Frisk, Michael; Le, Christopher; Shen, Xin; Røe, Åsmund Treu; Hou, Yufeng & Manfra, Ornella [Vis alle 24 forfattere av denne artikkelen] (2021). Etiology-dependent impairment of diastolic cardiomyocyte calcium homeostasis in heart failure with preserved ejection fraction. Journal of the American College of Cardiology. ISSN 0735-1097. 77(4), s. 405–419. doi: 10.1016/j.jacc.2020.11.044. Fulltekst i vitenarkiv Vis sammendrag

  Background Whereas heart failure with reduced ejection fraction (HFrEF) is associated with ventricular dilation and markedly reduced systolic function, heart failure with preserved ejection fraction (HFpEF) patients exhibit concentric hypertrophy and diastolic dysfunction. Impaired cardiomyocyte Ca2+ homeostasis in HFrEF has been linked to disruption of membrane invaginations called t-tubules, but it is unknown if such changes occur in HFpEF. Objectives This study examined whether distinct cardiomyocyte phenotypes underlie the heart failure entities of HFrEF and HFpEF. Methods T-tubule structure was investigated in left ventricular biopsies obtained from HFrEF and HFpEF patients, whereas cardiomyocyte Ca2+ homeostasis was studied in rat models of these conditions. Results HFpEF patients exhibited increased t-tubule density in comparison with control subjects. Super-resolution imaging revealed that higher t-tubule density resulted from both tubule dilation and proliferation. In contrast, t-tubule density was reduced in patients with HFrEF. Augmented collagen deposition within t-tubules was observed in HFrEF but not HFpEF hearts. A causative link between mechanical stress and t-tubule disruption was supported by markedly elevated ventricular wall stress in HFrEF patients. In HFrEF rats, t-tubule loss was linked to impaired systolic Ca2+ homeostasis, although diastolic Ca2+ removal was also reduced. In contrast, Ca2+ transient magnitude and release kinetics were largely maintained in HFpEF rats. However, diastolic Ca2+ impairments, including reduced sarco/endoplasmic reticulum Ca2+-ATPase activity, were specifically observed in diabetic HFpEF but not in ischemic or hypertensive models. Conclusions Although t-tubule disruption and impaired cardiomyocyte Ca2+ release are hallmarks of HFrEF, such changes are not prominent in HFpEF. Impaired diastolic Ca2+ homeostasis occurs in both conditions, but in HFpEF, this mechanism for diastolic dysfunction is etiology-dependent.

• Norden, Einar Sjaastad; Bendiksen, Bård Andre; Andresen, Henriette; Bergo, Kaja Knudsen; Espe, Emil Knut Stenersen & Hasic, Almira [Vis alle 12 forfattere av denne artikkelen] (2021). Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload. ESC Heart Failure. 8(2), s. 918–927. doi: 10.1002/ehf2.13177. Fulltekst i vitenarkiv
• Altara, Raffaele; Silva, Gustavo Jose Justo; Frisk, Michael; Spelta, Francesco; Zouein, Fouad A. & Louch, William Edward [Vis alle 8 forfattere av denne artikkelen] (2020). Cardioprotective Effects of the Novel Compound Vastiras in a Preclinical Model of End-Organ Damage. Hypertension. ISSN 0194-911X. 75(5), s. 1195–1204. doi: 10.1161/HYPERTENSIONAHA.120.14704. Fulltekst i vitenarkiv
• Bergo, Kaja Knudsen; Larstorp, Anne Cecilie Kjeldsen; Hoffmann, Pavel; Hjørnholm, Ulla; Cataliotti, Alessandro & Høieggen, Aud [Vis alle 8 forfattere av denne artikkelen] (2020). Renal sympathetic denervation lowers systemic vascular resistance in true treatment-resistant hypertension. Blood Pressure. ISSN 0803-7051. s. 1–10. doi: 10.1080/08037051.2020.1789446. Fulltekst i vitenarkiv Vis sammendrag

  Purpose Renal sympathetic denervation (RDN) is again gaining interest as recent well-designed trials have demonstrated reduced ambulatory blood pressure (BP) after RDN. However, the hemodynamic mechanisms have not been elucidated. We aimed for the first time to investigate the effect of RDN on the “Hallmark of Hypertension” namely increased systemic vascular resistance index (SVRI). Materials and methods We investigated SVRI change in patients with true treatment-resistant hypertension randomised to RDN (n = 9) or drug adjusted control (n = 9). Treatment-resistant hypertension was defined as office systolic BP ≥ 140 mmHg despite ≥ 3 antihypertensive drugs including a diuretic. True treatment-resistant hypertension was confirmed prior to inclusion with ambulatory daytime systolic BP ≥ 135 mmHg immediately after witnessed intake of antihypertensive drugs. Hemodynamic variables were recorded with thoracic impedance cardiography at baseline and at three and six months follow-up after RDN. This non-invasive method also guided further tailoring of drug treatment in the control group aiming to normalise hemodynamic variables and BP. Results From three to six months follow-up after RDN, SVRI decreased with a median of −611 dyn*s*m2/cm5 [IQR −949 to −267] (p < 0.01), while supine mean BP decreased with a median of −11 mmHg [IQR −21 to −3] (p = 0.02). In the same period, SVRI in the control group was reduced with −674 dyn*s*m2/cm5 [IQR −1,309 to −340] (p < 0.01), while supine mean BP decreased with −15 mmHg [IQR −29 to −6] (p = 0.01). Thus, hemodynamic variables and BP in the two groups normalised in parallel. Conclusion Our data suggest that in patients with true treatment-resistant hypertension, renal sympathetic denervation lowers BP by reducing systemic vascular resistance of similar size as in the control group with careful individual selection of antihypertensive drugs and dose titration.

• Røe, Åsmund Treu; Ruud, Marianne; Espe, Emil Knut Stenersen; Manfra, Ornella; Longobardi, S & Aronsen, Jan Magnus [Vis alle 16 forfattere av denne artikkelen] (2019). Regional diastolic dysfunction in post-infarction heart failure: role of local mechanical load and SERCA expression. Cardiovascular Research (CVR). ISSN 0008-6363. 115(4), s. 752–764. doi: 10.1093/cvr/cvy257. Fulltekst i vitenarkiv Vis sammendrag

  Aims: Regional heterogeneities in contraction contribute to heart failure with reduced ejection fraction (HFrEF). We aimed to determine whether regional changes in myocardial relaxation similarly contribute to diastolic dysfunction in post-infarction HFrEF, and to elucidate the underlying mechanisms. Methods and results: Using the magnetic resonance imaging phase-contrast technique, we examined local diastolic function in a rat model of post-infarction HFrEF. In comparison with sham-operated animals, post-infarction HFrEF rats exhibited reduced diastolic strain rate adjacent to the scar, but not in remote regions of the myocardium. Removal of Ca2+ within cardiomyocytes governs relaxation, and we indeed found that Ca2+ transients declined more slowly in cells isolated from the adjacent region. Resting Ca2+ levels in adjacent zone myocytes were also markedly elevated at high pacing rates. Impaired Ca2+ removal was attributed to a reduced rate of Ca2+ sequestration into the sarcoplasmic reticulum (SR), due to decreased local expression of the SR Ca2+ ATPase (SERCA). Wall stress was elevated in the adjacent region. Using ex vivo experiments with loaded papillary muscles, we demonstrated that high mechanical stress is directly linked to SERCA down-regulation and slowing of relaxation. Finally, we confirmed that regional diastolic dysfunction is also present in human HFrEF patients. Using echocardiographic speckle-tracking of patients enrolled in the LEAF trial, we found that in comparison with controls, post-infarction HFrEF subjects exhibited reduced diastolic train rate adjacent to the scar, but not in remote regions of the myocardium. Conclusion: Our data indicate that relaxation varies across the heart in post-infarction HFrEF. Regional diastolic dysfunction in this condition is linked to elevated wall stress adjacent to the infarction, resulting in down-regulation of SERCA, disrupted diastolic Ca2+ handling, and local slowing of relaxation.

• Lipsett, David Bruce; Frisk, Michael; Aronsen, Jan Magnus; Norden, Einar Sjaastad; Buonarati, Olivia R. & Cataliotti, Alessandro [Vis alle 10 forfattere av denne artikkelen] (2019). Cardiomyocyte substructure reverts to an immature phenotype during heart failure. Journal of Physiology. ISSN 0022-3751. 597(7), s. 1833–1853. doi: 10.1113/JP277273. Fulltekst i vitenarkiv Vis sammendrag

  Reactivation of the fetal gene programme has been implicated as a driver of pathological cardiac remodelling. Here we examined whether pathological remodelling of cardiomyocyte substructure and function during heart failure (HF) reflects a reversion to an immature phenotype. Using scanning electron microscopy, we observed that Z‐grooves and t‐tubule openings at the cell surface appeared gradually during cardiac development, and disappeared during HF. Confocal and super‐resolution imaging within the cell interior revealed similar structural parallels; disorganization of t‐tubules in failing cells was strikingly reminiscent of the late stages of postnatal development, with fewer transverse elements and a high proportion of longitudinal tubules. Ryanodine receptors (RyRs) were observed to be laid down in advance of developing t‐tubules and similarly ‘orphaned’ in HF, although RyR distribution along Z‐lines was relatively sparse. Indeed, nanoscale imaging revealed coordinated packing of L‐type Ca2+ channels and RyRs into dyadic junctions during development, and orderly unpacking during HF. These findings support a ‘last in, first out’ paradigm, as the latest stages of dyadic structural development are reversed during disease. Paired imaging of t‐tubules and Ca2+ showed that the disorganized arrangement of dyads in immature and failing cells promoted desynchronized and slowed Ca2+ release in these two states. However, while developing cells exhibited efficient triggering of Ca2+ release at newly formed dyads, dyadic function was impaired in failing cells despite similar organization of Ca2+ handling proteins. Thus, pathologically deficient Ca2+ homeostasis during HF is only partly linked to the re‐emergence of immature subcellular structure, and additionally reflects lost dyadic functionality.

• Ghali, Rana; Raffaele, Altara; Louch, William Edward; Cataliotti, Alessandro; Mallat, Ziad & Kaplan, Abdullah [Vis alle 8 forfattere av denne artikkelen] (2018). IL-33 (interleukin 33)/sST2 (soluble suppression of tumorigenicity 2) axis in hypertension and heart failure. Hypertension. ISSN 0194-911X. 72(4), s. 818–828. doi: 10.1161/HYPERTENSIONAHA.118.11157. Fulltekst i vitenarkiv
• Raffaele, Altara; Ghali, Rana; Mallat, Ziad; Cataliotti, Alessandro; Booz, George W. & Zouein, Fouad (2018). Conflicting vascular and metabolic impact of the IL-33/sST2 axis. Cardiovascular Research (CVR). ISSN 0008-6363. 114(12), s. 1578–1594. doi: 10.1093/cvr/cvy166. Fulltekst i vitenarkiv Vis sammendrag

  Interleukin 33 (IL-33), which is expressed by several immune cell types, endothelial and epithelial cells, and fibroblasts, is a cytokine of the IL-1 family that acts both intra- and extracellularly to either enhance or resolve the inflammatory response. Intracellular IL-33 acts in the nucleus as a regulator of transcription. Once released from cells by mechanical stress, inflammatory cytokines, or necrosis, extracellular IL-33 is proteolytically processed to act in an autocrine/paracrine manner as an ‘alarmin’ on neighbouring or various immune cells expressing the ST2 receptor. Thus, IL-33 may serve an important role in tissue preservation and repair in response to injury; however, the actions of IL-33 are dampened by a soluble form of ST2 (sST2) that acts as a decoy receptor and is produced by endothelial and certain immune cells. Accumulating evidence supports the conclusion that sST2 is a biomarker of vascular health with diagnostic and/or prognostic value in various cardiovascular diseases, including coronary artery disease, myocardial infarction, atherosclerosis, giant-cell arteritis, acute aortic dissection, and ischaemic stroke, as well as obesity and diabetes. Although sST2 levels are positively associated with cardiovascular disease severity, the assumption that IL-33 is always beneficial is naïve. It is increasingly appreciated that the pathophysiological importance of IL-33 is highly dependent on cellular and temporal expression. Although IL-33 is atheroprotective and may prevent obesity and type 2 diabetes by regulating lipid metabolism, IL-33 appears to drive endothelial inflammation. Here, we review the current knowledge of the IL-33/ST2/sST2 signalling network and discuss its pathophysiological and translational implications in cardiovascular diseases.

• Kolstad, Terje R Selnes; Brink, Jonas van Den; Macquaide, Niall; Lunde, Per Kristian; Frisk, Michael & Aronsen, Jan Magnus [Vis alle 13 forfattere av denne artikkelen] (2018). Ryanodine receptor dispersion disrupts Ca2+ release in failing cardiac myocytes. eLIFE. 7. doi: 10.7554/eLife.39427. Fulltekst i vitenarkiv Vis sammendrag

  Reduced cardiac contractility during heart failure (HF) is linked to impaired Ca2+ release from Ryanodine Receptors (RyRs). We investigated whether this deficit can be traced to nanoscale RyR reorganization. Using super-resolution imaging, we observed dispersion of RyR clusters in cardiomyocytes from post-infarction HF rats, resulting in more numerous, smaller clusters. Functional groupings of RyR clusters which produce Ca2+ sparks (Ca2+ release units, CRUs) also became less solid. An increased fraction of small CRUs in HF was linked to augmented ‘silent’ Ca2+ leak, not visible as sparks. Larger multi-cluster CRUs common in HF also exhibited low fidelity spark generation. When successfully triggered, sparks in failing cells displayed slow kinetics as Ca2+ spread across dispersed CRUs. During the action potential, these slow sparks protracted and desynchronized the overall Ca2+ transient. Thus, nanoscale RyR reorganization during HF augments Ca2+ leak and slows Ca2+ release kinetics, leading to weakened contraction in this disease.

• Raffaele, Altara; Fouad, A. Zouein; Brandão, Rita Dias; Bajestani, Saeed N.; Cataliotti, Alessandro & Booz, George W. (2018). In Silico Analysis of Differential Gene Expression in Three Common Rat Models of Diastolic Dysfunction. Frontiers in Cardiovascular Medicine. 5(11). doi: 10.3389/fcvm.2018.00011. Fulltekst i vitenarkiv Vis sammendrag

  Standard therapies for heart failure with preserved ejection fraction (HFpEF) have been unsuccessful, demonstrating that the contribution of the underlying diastolic dysfunction pathophysiology differs from that of systolic dysfunction in heart failure and currently is far from being understood. Complicating the investigation of HFpEF is the contribution of several comorbidities. Here, we selected three established rat models of diastolic dysfunction defined by three major risk factors associated with HFpEF and researched their commonalities and differences. The top differentially expressed genes in the left ventricle of Dahl salt sensitive (Dahl/SS), spontaneous hypertensive heart failure (SHHF), and diabetes 1 induced HFpEF models were derived from published data in Gene Expression Omnibus and used for a comprehensive interpretation of the underlying pathophysiological context of each model. The diversity of the underlying transcriptomic of the heart of each model is clearly observed by the different panel of top regulated genes: the diabetic model has 20 genes in common with the Dahl/SS and 15 with the SHHF models. Advanced analytics performed in Ingenuity Pathway Analysis (IPA®) revealed that Dahl/SS heart tissue transcripts triggered by upstream regulators lead to dilated cardiomyopathy, hypertrophy of heart, arrhythmia, and failure of heart. In the heart of SHHF, a total of 26 genes were closely linked to cardiovascular disease including cardiotoxicity, pericarditis, ST-elevated myocardial infarction, and dilated cardiomyopathy. IPA Upstream Regulator analyses revealed that protection of cardiomyocytes is hampered by inhibition of the ERBB2 plasma membrane-bound receptor tyrosine kinases. Cardioprotective markers such as natriuretic peptide A (NPPA), heat shock 27 kDa protein 1 (HSPB1), and angiogenin (ANG) were upregulated in the diabetes 1 induced model; however, the model showed a different underlying mechanism with a majority of the regulated genes involved in metabolic disorders. In conclusion, our findings suggest that multiple mechanisms may contribute to diastolic dysfunction and HFpEF, and thus drug therapies may need to be guided more by phenotypic characteristics of the cardiac remodeling events than by the underlying molecular processes.

• Holditch, Sara J.; Schreiber, Claire A.; Harris, Peter C.; LaRusso, Nicholas F.; Ramirez-Alvarado, Marina & Cataliotti, Alessandro [Vis alle 8 forfattere av denne artikkelen] (2017). B-type natriuretic peptide overexpression ameliorates hepatorenal fibrocystic disease in a rat model of polycystic kidney disease. Kidney International. ISSN 0085-2538. 92(3), s. 657–668. doi: 10.1016/j.kint.2017.02.017. Fulltekst i vitenarkiv
• Giordano, Mauro; Ciarambino, Tiziana; Castellino, Pietro; Malatino, Lorenzo; Cataliotti, Alessandro & Rinaldi, Luca [Vis alle 8 forfattere av denne artikkelen] (2017). Seasonal variations of hyponatremia in the emergency department: Age-related changes. American Journal of Emergency Medicine. ISSN 0735-6757. 35(5), s. 749–752. doi: 10.1016/j.ajem.2017.01.018. Fulltekst i vitenarkiv
• Raffaele, Altara; Giordano, Mauro; Norden, Einar Sjaastad; Cataliotti, Alessandro; Kurdi, Mazen & Bajestani, Saeed N. [Vis alle 7 forfattere av denne artikkelen] (2017). Targeting obesity and diabetes to treat heart failure with preserved ejection fraction. Frontiers in Endocrinology. 8:160, s. 1–13. doi: 10.3389/fendo.2017.00160. Fulltekst i vitenarkiv
• Giordano, Mauro; Ciarambino, Tiziana; Priore, Emanuela Lo; Castellino, Pietro; Malatino, Lorenzo & Cataliotti, Alessandro [Vis alle 8 forfattere av denne artikkelen] (2017). Serum sodium correction rate and the outcome in severe hyponatremia. American Journal of Emergency Medicine. ISSN 0735-6757. 35(11), s. 1691–1694. doi: 10.1016/j.ajem.2017.05.050. Fulltekst i vitenarkiv
• Buonacera, Agata; Boukhris, Marouane; Tomasello, Salvatore D.; Campagna, Andrea; Cilia, Chiara & Tripepi, Giovanni [Vis alle 14 forfattere av denne artikkelen] (2016). Impact of left ventricular remodeling and renal function on 24 h-ECG recordings and cardiovascular outcome in elderly hypertensive patients. European journal of internal medicine. ISSN 0953-6205. 29, s. 71–77. doi: 10.1016/j.ejim.2016.01.001. Fulltekst i vitenarkiv
• Bellavia, Diego; Cataliotti, Alessandro; Clemenza, Francesco; Baravoglia, Cesar Hernandez; Luca, Angelo & Traina, Marcello [Vis alle 10 forfattere av denne artikkelen] (2015). Long-Term structural and functional myocardial adaptations in healthy living kidney donors: A pilot study. PLOS ONE. 10:e0142103, s. 1–15. doi: 10.1371/journal.pone.0142103. Fulltekst i vitenarkiv
• Røsjø, Helge; Dahl, Mai Britt; Pedersen, Marit Holmefjord; Røysland, Ragnhild; Brynildsen, Jon & Cataliotti, Alessandro [Vis alle 10 forfattere av denne artikkelen] (2015). Influence of glycosylation on diagnostic and prognostic accuracy of N-terminal pro-b-type natriuretic peptide in acute dyspnea: Data from the Akershus cardiac examination 2 study. Clinical Chemistry. ISSN 0009-9147. 61(8), s. 1087–1097. doi: 10.1373/clinchem.2015.239673. Fulltekst i vitenarkiv
• Holditch, Sara J.; Schreiber, Claire A.; Nini, Ryan; Tonne, Jason M.; Peng, Kah-Whye & Geurts, Aron [Vis alle 10 forfattere av denne artikkelen] (2015). B-type natriuretic peptide deletion leads to progressive hypertension, associated organ damage, and reduced survival: Novel model for human hypertension. Hypertension. ISSN 0194-911X. 66(1), s. 199–210. doi: 10.1161/HYPERTENSIONAHA.115.05610. Fulltekst i vitenarkiv
• Aspelin, Trude; Eriksen, Morten; Ilebekk, Arnfinn; Cataliotti, Alessandro; Carlson, Cathrine Rein & Lyberg, Torstein (2014). ß-blockade abolishes the augmented cardiac tPA release induced by transactivation of heterodimerised bradykinin receptor-2 and b2-adrenergic receptor in vivo. Thrombosis and Haemostasis. ISSN 0340-6245. 112(5), s. 951–959. doi: 10.1160/TH14-01-0059. Fulltekst i vitenarkiv

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• Espino-Gonzalez, Ever; Tickle, Peter G.; Altara, Raffaele; Booz, George W.; Cataliotti, Alessandro & Roberts, Lee D. [Vis alle 8 forfattere av denne artikkelen] (2024). Reply: Navigating Nutritional Nuances in the Research of Heart Failure With Preserved Ejection Fraction. JACC: Basic to Translational Science. ISSN 2452-302X. 9(3), s. 403–403. doi: 10.1016/j.jacbts.2024.01.014. Fulltekst i vitenarkiv
• Norden, Einar Sjaastad; Bergo, Kaja Knudsen; Zhang, Lili; Aronsen, Jan Magnus; Hasic, Almira & Hussain, I. [Vis alle 8 forfattere av denne artikkelen] (2016). Anti-hypertrophic effects of LCZ696 in chronic cardiac pressure overload. Fulltekst i vitenarkiv
• Parvan, Reza; Silva, Gustavo Jose Justo & Cataliotti, Alessandro (2026). Non-coding RNAs for diagnosis and treatment of heart failure. Universitetet i Oslo. ISSN 9788234808777. Fulltekst i vitenarkiv Vis sammendrag

  Heart failure (HF) is a major cause of hospitalization and death worldwide, and its prevalence is expected to increase. Heart failure with preserved ejection fraction (HFpEF) is particularly challenging because it is a complex, multisystem disease influenced by obesity, diabetes, hypertension, and kidney dysfunction. Current approaches have important limitations, creating a need for reliable biomarkers and new therapeutic targets. This thesis investigated the role of microRNAs (miRNAs) in HF diagnosis, prognosis, and pathophysiology, with a focus on HFpEF. A combination of large-scale clinical analyses and experimental studies using established animal models was applied. The clinical analyses showed that specific circulating miRNAs are associated with HF and can help distinguish HFpEF from other forms of HF. Combining miRNAs with conventional biomarkers improved diagnostic performance. Several miRNA patterns were also associated with HF development, hospitalization, and death, suggesting their potential value for risk prediction. Complementary preclinical studies identified panels of circulating miRNAs that reflect cardiac dysfunction and may serve as diagnostic biomarkers. Animal models resembling the different HF etiologies enabled the identification of miRNAs altered in cardiac tissue and associated with cardiac hypertrophy, diastolic dysfunction, and kidney abnormalities. Additionally, it has been shown that the miRNA expression pattern depends on the underlying disease and comorbidities. Lastly, we demonstrated that these miRNAs are involved in processes relevant to HF, including TGF-β, Hippo, FOXO, and NF-κB signalling. Overall, this thesis supports miRNAs as promising biomarkers for HF diagnosis and prognosis and provides evidence that they may contribute to HFpEF mechanisms. The findings demonstrate the value of combining clinical and experimental approaches to identify disease-relevant miRNAs. Further studies are needed to validate these findings and support their translation into clinical practice.

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