A SNP in the gene encoding for FSAP is a risk factor for atherosclerosis 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 Neurosc 2015) and are protected against thrombosis (Subramaniam et al, Thromb & Haem 2015).
Furthermore, we have identified a novel substrate for FSAP in the circulation, tissue factor pathway inhibitor, complement proteins and fibrinogen, 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).
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 (manuscript in preparation).
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, 2019).
We have established methods to produce recombinant FSAP domains in bacteria for detailed structure-function studies (manuscript in preparation).
We have established the role of protease activated receptors in mediating the cellular effects of FSAP (Byskov et al, Atherosclerosis, 2016 and manuscript in preparation)
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, 2013).
We have characterized the pathways and transcription factors regulating the expression of FSAP in hepatocytes (Leiting et al, J Biol Chem, 2015) and have identified novel genes involved in this regulation through GWAS studies (Olsson et al, J Thromb & Haem 2017)