title: Inhibition of PCSK9: a novel approach for the treatment of dyslipidemia.
abstract: Hypercholesterolemia is a key risk factor for atherosclerosis. Because of its role in controlling serum levels of low-density lipoprotein (LDL) through the regulation of hepatic LDL-receptors, the recently discovered proprotein convertase subtilisin/kexin-type 9 (PCSK9) is a promising pharmacological target. This review aims to discuss the impact of natural mutations in the PCSK9 gene on cholesterol metabolism and thus coronary artery disease, as well as molecular mechanisms and therapeutic strategies for PCSK9 inhibition. We summarize data from recent clinical trials using fully humanized monoclonal antibodies, showing that PCSK9 inhibition results in a significant reduction in LDL-cholesterol in high-risk cardiovascular patients. Future studies will have to address the long-term safety and efficacy as well as the impact of PCSK9-targeting therapies on cardiovascular outcomes.
authors.affiliation: aDepartment of Medicine and Cardiology, German Heart Institute Berlin bCardiovascular Research Center (CCR), Institute of Pharmacology, Charité Universitätsmedizin-Berlin, Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Stawowy
authors.forename: Isabell A
authors.initials: IA
authors.lastname: Just
authors.forename: Elena
authors.initials: E
authors.lastname: Kaschina
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D015195:Drug Design; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D015842:Serine Proteinase Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases