Key words
- Organ donation
- Machine perfusion
- Mitochondria
- Interdisciplinary
- Comparative physiology
Research
- Reducing ischemia reperfusion injury in the heart
- Improve organs for transplantation
- Sterile inflammation in acute myocardial infarction
- Mitochondrial resistance to low oxygen
- Calcification of aortic heart valves
Teaching
- Cardio-pulmonary physiology for second year medical students
Publications
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Torp, May-Kristin; Ranheim, Trine; Schjalm, Camilla; Hjorth, Marit; Heiestad, Christina Mathisen & Dalen, Knut Tomas
[Show all 13 contributors for this article]
(2022).
Intracellular Complement Component 3 Attenuated Ischemia-Reperfusion Injury in the Isolated Buffer-Perfused Mouse Heart and Is Associated With Improved Metabolic Homeostasis.
Frontiers in Immunology.
ISSN 1664-3224.
13.
doi:
10.3389/fimmu.2022.870811.
Full text in Research Archive
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The innate immune system is rapidly activated during myocardial infarction and blockade of extracellular complement system reduces infarct size. Intracellular complement, however, appears to be closely linked to metabolic pathways and its role in ischemia-reperfusion injury is unknown and may be different from complement activation in the circulation. The purpose of the present study was to investigate the role of intracellular complement in isolated, retrogradely buffer-perfused hearts and cardiac cells from adult male wild type mice (WT) and from adult male mice with knockout of complement component 3 (C3KO). Main findings: (i) Intracellular C3 protein was expressed in isolated cardiomyocytes and in whole hearts, (ii) after ischemia-reperfusion injury, C3KO hearts had larger infarct size (32 ± 9% in C3KO vs. 22 ± 7% in WT; p=0.008) and impaired post-ischemic relaxation compared to WT hearts, (iii) C3KO cardiomyocytes had lower basal oxidative respiration compared to WT cardiomyocytes, (iv) blocking mTOR decreased Akt phosphorylation in WT, but not in C3KO cardiomyocytes, (v) after ischemia, WT hearts had higher levels of ATP, but lower levels of both reduced and oxidized nicotinamide adenine dinucleotide (NADH and NAD+, respectively) compared to C3KO hearts. Conclusion: intracellular C3 protected the heart against ischemia-reperfusion injury, possibly due to its role in metabolic pathways important for energy production and cell survival.
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Li, Yuchuan; Torp, May-Kristin; Norheim, Frode; Khanal, Prabhat; Kimmel, Alan R. & Stensløkken, Kåre-Olav
[Show all 8 contributors for this article]
(2020).
Isolated Plin5-deficient cardiomyocytes store less lipid droplets than normal, but without increased sensitivity to hypoxia .
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids.
ISSN 1388-1981.
1866(4).
doi:
10.1016/j.bbalip.2020.158873.
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Plin5 is abundantly expressed in the heart where it binds to lipid droplets (LDs) and facilitates physical interaction between LDs and mitochondria. We isolated cardiomyocytes from adult Plin5+/+ and Plin5-/- mice to study the role of Plin5 for fatty acid uptake, LD accumulation, fatty acid oxidation, and tolerance to hypoxia. Cardiomyocytes isolated from Plin5-/- mice cultured with oleic acid stored less LDs than Plin5+/+, but comparable levels to Plin5+/+ cardiomyocytes when adipose triglyceride lipase activity was inhibited. The ability to oxidize fatty acids into CO2 was similar between Plin5+/+ and Plin5-/- cardiomyocytes, but Plin5-/- cardiomyocytes had a transient increase in intracellular fatty acid oxidation intermediates. After pre-incubation with oleic acids, Plin5-/- cardiomyocytes retained a higher content of glycogen and showed improved tolerance to hypoxia compared to Plin5+/+. In isolated, perfused hearts, deletion of Plin5 had no important effect on ventricular pressures or infarct size after ischemia. Old Plin5-/- mice had reduced levels of cardiac triacylglycerides, increased heart weight, and apart from modest elevated expression of mRNAs for beta myosin heavy chain Myh7 and the fatty acid transporter Cd36, other genes involved in fatty acid oxidation, glycogen metabolism and glucose utilization were essentially unchanged by removal of Plin5. Plin5 seems to facilitate cardiac LD storage primarily by repressing adipose triglyceride lipase activity without altering cardiac fatty acid oxidation capacity. Expression of Plin5 and cardiac LD content of isolated cardiomyocytes has little importance for tolerance to acute hypoxia and ischemia, which contrasts the protective role for Plin5 in mouse models during myocardial ischemia.
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Bogdanova, Mariia; Zabirnyk, Arsenii; Malashicheva, Anna; Zihlavnikova, Katarina; Karlsen, Tommy Aleksander & Kaljusto, Mari-Liis
[Show all 13 contributors for this article]
(2019).
Interstitial cells in calcified aortic valves have reduced differentiation potential and stem cell-like properties.
Scientific Reports.
ISSN 2045-2322.
9:12934,
p. 1–13.
doi:
10.1038/s41598-019-49016-0.
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Valve interstitial cells (VICs) are crucial in the development of calcific aortic valve disease. The purpose of the present investigation was to compare the phenotype, differentiation potential and stem cell-like properties of cells from calcified and healthy aortic valves. VICs were isolated from human healthy and calcified aortic valves. Calcification was induced with osteogenic medium. Unlike VICs from healthy valves, VICs from calcified valves cultured without osteogenic medium stained positively for calcium deposits with Alizarin Red confirming their calcific phenotype. Stimulation of VICs from calcified valves with osteogenic medium increased calcification (p = 0.02), but not significantly different from healthy VICs. When stimulated with myofibroblastic medium, VICs from calcified valves had lower expression of myofibroblastic markers, measured by flow cytometry and RT-qPCR, compared to healthy VICs. Contraction of collagen gel (a measure of myofibroblastic activity) was attenuated in cells from calcified valves (p = 0.04). Moreover, VICs from calcified valves, unlike cells from healthy valves had lower potential to differentiate into adipogenic pathway and lower expression of stem cell-associated markers CD106 (p = 0.04) and aldehyde dehydrogenase (p = 0.04). In conclusion, VICs from calcified aortic have reduced multipotency compared to cells from healthy valves, which should be considered when investigating possible medical treatments of aortic valve calcification.
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Fagernes, Cathrine Elisabeth; Stensløkken, Kåre-Olav; Kjendseth, Åsmund Røhr; Berenbrink, Michael; Ellefsen, Stian & Nilsson, Göran Erik
(2017).
Extreme anoxia tolerance in
crucian carp and goldfish through
neofunctionalization of duplicated
genes creating a new ethanol-
producing pyruvate decarboxylase
pathway.
Scientific Reports.
ISSN 2045-2322.
doi:
10.1038/s41598-017-07385-4.
Full text in Research Archive
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Bliksøen, Marte; Rutkovskiy, Arkady; Vaage, Ingvar Jarle & Stensløkken, Kåre-Olav
(2017).
Mode of perfusion influences infarct size, coronary flow and stress kinases in the isolated mouse heart.
Acta Physiologica.
ISSN 1748-1708.
220(1),
p. 36–46.
doi:
10.1111/apha.12773.
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Aim: The isolated, retrogradely perfused heart (modified Langendorff
model) is a widely used method in experimental heart research. The presence
of an intraventricular balloon is necessary to get functional measurements.
We have previously shown that the balloon induces
phosphorylation of some suggested cardioprotective mitogen-activated protein
kinases (MAPK): P38-MAPK, ERK 1/2 and JNK. We hypothesized
that the balloon could influence cardioprotection, protect against ischaemia
reperfusion injury and interfere with coronary flow.
Methods and Results: Isolated mouse hearts were perfused for 5, 10, 20,
40 and 60 min with a balloon in the left ventricle. We found a wavelike
phosphorylation of all MAPK while AKT displayed a gradual dephosphorylation
when compared to non-perfused hearts. Hearts were subjected to
20 min of stabilization with or without the balloon, followed by 35 min of
ischaemia and 120 min of reperfusion. Although the MAPK were phosphorylated,
the infarcts were larger in the balloon group. When the balloon
was present during the entire protocol, compared to removal at the end of
ischaemia, the infarct size was also larger, especially in the endocardial
layer. The balloon reduced post-ischaemic endocardial coronary flow,
despite a higher average flow, indicating a hyperperfused epicard. Blocking
the balloon-induced ERK 1/2 phosphorylation during stabilization did not
affect infarct size. The effect of post-conditioning was influenced by the
balloon, showing reduced infarct size when the balloon was present.
Conclusion: The balloon used for pressure measurements may contributes
to cell death possibly by reducing endocardial coronary flow.
Keywords coronary flow, kinases, Langendorff, perfusion, post-conditioning,
pre-conditioning.
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Nilsson, Göran Erik; Vaage, Ingvar Jarle & Stensløkken, Kåre-Olav
(2015).
Oxygen- and temperature-dependent expression of survival protein kinases in crucian carp (carassius carassius) heart and brain.
American Journal of Physiology. Regulatory Integrative and Comparative Physiology.
ISSN 0363-6119.
308(1),
p. R50–R61.
doi:
10.1152/ajpregu.00094.2014.
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Røsjø, Helge; Stridsberg, Mats; Florholmen, Geir; Stensløkken, Kåre-Olav; Ottesen, Anett Hellebø & Sjaastad, Ivar
[Show all 12 contributors for this article]
(2012).
Secretogranin II; a Protein Increased in the Myocardium and Circulation in Heart Failure with Cardioprotective Properties.
PLOS ONE.
ISSN 1932-6203.
7(5).
doi:
10.1371/journal.pone.0037401.
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Ellefsen, Stian & Stensløkken, Kåre-Olav
(2010).
Gene-family profiling: a normalization-free real-time RT-PCR approach with increased physiological resolution.
Physiological Genomics.
ISSN 1094-8341.
42(1),
p. 1–4.
doi:
10.1152/physiolgenomics.00196.2009.
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Stensløkken, Kåre-Olav; Ellefsen, Stian; Larsen, Helene Kile; Vaage, Ingvar Jarle & Nilsson, Göran Erik
(2010).
Expression of heat shock proteins in anoxic crucian carp (Carassius carassius): support for cold as a preparatory cue for anoxia.
American Journal of Physiology. Regulatory Integrative and Comparative Physiology.
ISSN 0363-6119.
298(6),
p. R1499–R1508.
doi:
10.1152/ajpregu.00675.2009.
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Ellefsen, Stian; Stensløkken, Kåre-Olav; Fagernes, Cathrine; Kristensen, Tom A. & Nilsson, Göran E.
(2009).
Expression of genes involved in GABAergic neurotransmission in anoxic crucian carp (Carassius carassius) brain.
Physiological Genomics.
ISSN 1094-8341.
p. 61–68.
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Ellefsen, Stian; Stensløkken, Kåre-Olav; Fagernes, Cathrine Elisabeth; Kristensen, Tom & Nilsson, Gøran Erik
(2009).
Expression of genes involved in GABAergic neurotransmission in anoxic crucian carp brain (Carassius carassius).
Physiological Genomics.
ISSN 1094-8341.
36(2),
p. 61–68.
doi:
10.1152/physiolgenomics.90301.2008.
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Stensløkken, Kåre-Olav; Rutkovskiy, Arkady; Kaljusto, Mari-Liis; Hafstad, Anne Dragøy; Larsen, Terje Steinar & Vaage, Ingvar Jarle
(2009).
Inadvertent phosphorylation of survival kinases in isolated perfused hearts: a word of caution.
Basic Research in Cardiology.
ISSN 0300-8428.
104,
p. 412–423.
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Stensløkken, Kåre-Olav; Ellefsen, Stian; Stecyk, Jonathan A. W.; Dahl, Mai Brit; Nilsson, Göran E. & Vaage, Jarle
(2008).
Differential regulation of AMP-activated kinase and AKT kinase in response to oxygen availability in crucian carp (Carassius carassius).
American Journal of Physiology. Regulatory Integrative and Comparative Physiology.
ISSN 0363-6119.
p. 1803–1814.
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Ellefsen, Stian; Sandvik, Guro K.; Larsen, Helene K.; Stensløkken, Kåre-Olav; Hov, Dag Are S. & Kristensen, Tom A.
[Show all 7 contributors for this article]
(2008).
Expression of genes involved in excitatory neurotransmission in anoxic crucian carp (Carassius carassius) brain.
Physiological Genomics.
ISSN 1094-8341.
p. 5–17.
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Ellefsen, Stian; Sandvik, Guro Katrine; Larsen, Helene Kile; Stensløkken, Kåre-Olav; Hov, Dag Are Steenhoff & Kristensen, Tom
[Show all 7 contributors for this article]
(2008).
Expression of genes involved in excitatory neurotransmission in anoxic crucian carp (Carassius carassius) brain.
Physiological Genomics.
ISSN 1094-8341.
35,
p. 5–17.
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Stensløkken, Kåre-Olav; Ellefsen, Stian; Stecyk, Jonathan Anthony William; Dahl, Mai Britt; Nilsson, Gøran Erik & Vaage, Jarle
(2008).
Differential regulation of AMP-activated kinase and AKT kinase in response to oxygen availability in crucian carp (Carassius carassius).
American Journal of Physiology. Regulatory Integrative and Comparative Physiology.
ISSN 0363-6119.
295(6),
p. R1803–R1814.
doi:
10.1152/ajpregu.90590.2008.
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Stensløkken, Kåre-Olav; Sundin, Lena & Nilsson, Gøran Erik
(2006).
Endothelin receptors in teleost fishes: cardiovascular effects and branchial distribution.
American Journal of Physiology. Regulatory Integrative and Comparative Physiology.
ISSN 0363-6119.
290.
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Stecyk, Jonathan A. W.; Stensløkken, Kåre-Olav; Farrell, Anthony P. & Nilsson, Gøran Erik
(2004).
Maintained cardiac pumping in anoxic crucian carp.
Science.
ISSN 0036-8075.
306,
p. 77–77.
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Stensløkken, Kåre-Olav; Sundin, Lena; Renshaw, Gillian M. C. & Nilsson, Gøran Erik
(2004).
Adenosinergic and cholinergic control mechanisms during hypoxia in the epaulette shark (Hemiscyllium ocellatum), with emphasis on branchial circulation.
Journal of Experimental Biology.
ISSN 0022-0949.
207,
p. 4451–4461.
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Stensløkken, Kåre-Olav; Sundin, Lena & Nilsson, Gøran Erik
(1999).
Cardiovascular and gill microcirculatory effects of endothelin-1 in Atlantic cod: evidence for pillar cell contraction.
Journal of Experimental Biology.
ISSN 0022-0949.
202,
p. 1151–1157.
Show summary
Endothelin-1 (ET-1) has been shown to cause a considerable increase in the vascular resistance of fish gills. In trout, recent evidence suggest that this is the result of pillar cell contraction in the gill lamellae. Using epi-illumination microscopy to observe the gill lamellae of anaesthetised Atlantic cod (Gadus morhua), we here show that ET-1 (100 ng kg-1, injected into the ventral aorta) causes an enlargement of the pillar cell diameter, consistent with pillar cell contraction, and a shift of intralamellar blood flow from the lamellar sheet to the outer marginal channels. Simultaneously, there was an increase in ventral aortic blood pressure, a fall in cardiac output, an increase in gill vascular resistance, and a fall in the oxygen tension of venous blood. All these effects were blocked by the ETA/ETB receptor antagonist bosentan (5 mg kg-1). Pillar cell contraction is likely to be a mechanism for matching the functional respiratory surface area with the momentary respiratory needs
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Gerber, Lucie; Helle-Valle, Tellef; Resseguier, Julien Alain Andre; Torp, May-Kristin; Dahl, Helge Andre & Nilsson, Göran Erik
[Show all 8 contributors for this article]
(2022).
Prolyl Hydroxylase Domains in the Anoxia Tolerant Crucian Carp (c. carassius): Insights into the Regulation of the HIF Response to Anoxia-Reoxygenation.
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Gerber, Lucie; Helle-Valle, Tellef; Resseguier, Julien Alain Andre; Torp, May-Kristin; Dahl, Helge Andre & Nilsson, Göran Erik
[Show all 8 contributors for this article]
(2022).
Prolyl Hydroxylase Domains in the Anoxia Tolerant Crucian Carp (c. carassius): Insights into the Regulation of the HIF Response to Anoxia-Reoxygenation.
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Gerber, Lucie; Torp, May-Kristin; Nilsson, Göran Erik; Stensløkken, Kåre-Olav & Lefevre, Sjannie
(2022).
Mitochondrial Functions in the Anoxia Tolerant Crucian Carp. .
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Gerber, Lucie; Torp, May-Kristin; Nilsson, Göran Erik; Lefevre, Sjannie & Stensløkken, Kåre-Olav
(2022).
Improving organ preservation: Another lesson from the champion of anoxia tolerance, the crucian carp (C. carassius).
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Gerber, Lucie; Torp, May-Kristin; Nilsson, Göran Erik; Lefevre, Sjannie & Stensløkken, Kåre-Olav
(2022).
Improving organ preservation: Another lesson from the champion of anoxia tolerance, the crucian carp (C. carassius).
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Røsjø, Helge; Stridsberg, M.; Florholmen, Geir; Stensløkken, Kåre-Olav; Sjaastad, Ivar & Husberg, Cathrine
[Show all 10 contributors for this article]
(2010).
Secretoneurin is a novel peptide increased in the myocardium and circulation in heart failure with cardioprotective properties.
European Heart Journal.
ISSN 0195-668X.
31,
p. 314–314.
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Ellefsen, Stian & Stensløkken, Kåre-Olav
(2010).
Gene-family profiling : a normalization-free real-time RT-PCR approach with increased physiological resolution.
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Bliksoen, M; Rutkovskiy, Arkady; Mariero, Lars Henrik; Vaage, Ingvar Jarle & Stensløkken, Kåre-Olav
(2010).
Phosphorylation of survival kinases is not a guarantee for protection of ischemia-reperfusion injury in the isolated, perfused mouse heart.
Cardiovascular Research (CVR).
ISSN 0008-6363.
87,
p. S85–S85.
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Rutkovskiy, Arkady; Mariero, Lars Henrik; Stensløkken, Kåre-Olav; Valen, Guro & Vaage, Ingvar Jarle
(2010).
Osmotic pressure regulates expression levels of cardiac aquaporins 1 and 4.
Cardiovascular Research (CVR).
ISSN 0008-6363.
87,
p. S104–S104.
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Mariero, Lars Henrik; Rutkovskiy, Arkady; Stensløkken, Kåre-Olav & Vaage, Ingvar Jarle
(2010).
May hyperoxic ventilation during early reperfusion increase infarct size?
Cardiovascular Research (CVR).
ISSN 0008-6363.
87,
p. S134–S134.
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Røsjø, Helge; Stridsberg, Mats; Florholmen, Geir; Stensløkken, Kåre-Olav; Sjaastad, Ivar & Husberg, Cathrine
[Show all 10 contributors for this article]
(2010).
Secretoneurin is a novel peptide increased in the myocardium and circulation in heart failure with cardioprotective properties.
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Røsjø, Helge; Stridsberg, M; Florholmen, Geir; Stensløkken, Kåre-Olav; Sjaastad, Ivar & Husberg, Cathrine
[Show all 10 contributors for this article]
(2010).
Secretoneurin: a novel protective agent increased in the myocardium and circulation in heart failure.
Hjerteforum.
ISSN 0802-1465.
23(1),
p. 101–102.
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Stecyk, Jonathan A. W.; Stensløkken, Kåre-Olav; Farrell, Anthony & Nilsson, Gøran Erik
(2005).
The beat goes on: The heart of anoxic crucian carp.
The FASEB Journal.
ISSN 0892-6638.
19(4),
p. A213–A214.
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Stensløkken, Kåre-Olav; Sundin, Lena; Renshaw, Gillian M. C. & Nilsson, Gøran Erik
(2003).
Effects of hypoxia and acetylcholine on branchial circulation in epaulette shark (Hemiscyllium ocellatum).
Comparative Biochemistry and Physiology A.
ISSN 1095-6433.
134,
p. S21–S21.
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Published
Jan. 29, 2014 2:23 PM
- Last modified
Jan. 19, 2023 10:23 AM