A SNP in the gene encoding for FSAP (HABP2, rs7050836) is a risk factor for carotid stenosis and stroke. We have performed numerous studies to understand the functions of FSAP with respect to neointima formation (Kannemeier et al, Faseb J, 2004; Sedding et al, J Exp Med, 2006; Daniel et al, J Thromb & Haem 2016) and arteriogenesis (Herold et al, Am J Trans Med, 2017). FSAP-/- mice exhibit a poor outcome after induction of stroke (Joshi et al, Eur J Neurosci 2015) and are protected against thrombosis (Subramaniam et al, Thromb & Haem 2015). Recombinant FSAP improves the outcome of stroke in two different mouse models (Kim et al, FasebJ, 2022).
We have shown that FSAP levels in patients are increased after stroke (Hanson et al, 2012, J Thromb Haem) and that FSAP activity is increased shortly after ischemic stroke but subsides thereafter (Jaeger et al, Acta Neurologica Scandinavica, 2023).
Furthermore, we have identified a novel substrate for FSAP in the circulation, tissue factor pathway inhibitor, complement proteins, fibrinogen, and histones, which will help to elucidate its function (Kanse et al, Arterioscler Thromb Vasc Biol, 2012 and J Immunol, 2012; Etscheid et al, Biochim Biophys Acta, 2018, Cui et al, Int J Mol Sci, 2022). We have established the role of protease-activated receptors in mediating the cellular effects of FSAP (Byskov et al, Atherosclerosis, 2016 and FasebJ, 2020)
We have expanded on the concept of tissue injury-mediated release of histones activating pro-FSAP to the activation of pro-FSAP by artificial surfaces (Sperling et al, ACS Appl Mat & Int, 2017), by neutrophil extracellular traps (NETs) (Grasso et al, 2018), and peptides identified by phage display (Berge-Seidl et al, ACS Chem Biol, 2022).
Using phage display and synthetic peptide substrate libraries, we have characterized the substrate specificity of FSAP and have developed new selective substrates (Kara et al, Thromb & Haem 2017). We have now extended these studies to synthetic peptide substrate libraries made of non-standard amino acids (Rut et al, Thromb Res, 2019) and used this to develop an assay for the continuous measurement of FSAP activity in plasma (Etscheid et al, Thromb Res, 2022)
We have established methods to produce recombinant FSAP domains in bacteria for detailed structure-function studies (Nielsen et al, 2019) and have mapped the effects of mutations in different domains on FSAP's functions (Kandanur et al, bioRxiv, 2025). We have also expressed FSAP and its fragments in insect cells to determine its structure (Kandanur et al, bioRxiv, 2025).
We have discovered a new function for FSAP in liver fibrosis by investigating its expression in liver fibrosis, and by determining the correlations of SNPs in the gene encoding for FSAP with the severity of liver fibrosis. FSAP-/- mice exhibit enhanced liver fibrosis. (Roderfeld et al, Liv Int 2009; Wasmuth et al, Hepatology, 2009, Borkham-Kamphorst et al, J Hepatol, 2014) as well as in regulating kidney function (Artunc et al, Pflugers Arch, 2022).
We have characterized the pathways and transcription factors regulating the expression of FSAP in hepatocytes (Leiting et al, J Biol Chem, 2015) and have performed a GWAS study to determine genetic determinants of FSAP activity (Olsson et al, J Thromb Haem, 2018).