title: Proprotein convertases in atherogenesis.
abstract: OBJECTIVE
  The proprotein convertases subtilisin/kexin (PCSKs) are endoproteases identified as activators of precursors from hormones and peptides. On the basis of the variety of substrates and regulation in disease, they have been recognized as mediators in atherogenesis. The discovery of PCSK9, which regulates low-density lipoprotein receptor cell membrane availability, has led to a resurgence of interest in these enzymes and their function in cardiovascular diseases.
  
  
  RESULTS
  Recent data demonstrate that PCSKs are expressed in human atheroma and are regulated in animal models of atherosclerosis. In animal models, inhibition of PCSKs, such as PCSK3, affects cell proliferation and migration as well as inflammation, reducing atherosclerosis. In addition, targeting PCSK9 lowers cholesterol levels and has now been demonstrated to lessen vascular lesion formation in mice. Experimentally investigated novel anti-PCSK9 strategies include genome editing and vaccination. Furthermore, studies show that PCSKs contribute to the initiation and progression of cardiometabolic risk factors, such as insulin resistance and obesity.
  
  
  CONCLUSIONS
  PCSKs affect cardiovascular diseases on multiple levels, including atherosclerotic lesion formation as well as their contribution to cardiometabolic risk factors. PCSK9 is a key regulator of plasma cholesterol levels, thereby potentially affecting atherosclerosis and has rapidly emerged as a pharmacological target.
authors.affiliation: Deutsches Herzzentrum Berlin, Department of Medicine/Cardiology, Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Stawowy
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology*; D006333:Heart Failure / Q000201:enzymology; D006801:Humans; D024821:Metabolic Syndrome / Q000201:enzymology; D043484:Proprotein Convertases / Q000378:metabolism*
chemical_list: D043484:Proprotein Convertases