title: Significance of Monoclonal PCSK9-Antibodies - New Approaches to the Therapy of Hypercholesterolemia.
abstract: Increased concentrations of low-density-lipoprotein (LDL)-cholesterol (LDL-C) and lipoprotein a (Lp(a)) are scientifically accepted, independent risk factors for the development of atherosclerosis. The complications of atherosclerosis occur early and more frequently. They are strongly linked with lifestyle factors and an increase of LDL-C concentrations in industrialized countries. A new therapeutic approach seems to be the modulation of the proprotein convertase subtilisin/kexin type 9 (PCSK9), which reduces the number of LDL-receptors at the cell membrane of the liver cells and thus increases the concentration of LDL-C in the blood. Results of current studies show, that in particular, a combination of PCSK9-AB and statins, independent of the dosage of the statins, is suitable to increase a reduction of LDL-C and Lp(a). This article gives an overview of the pathophysiology, the current study and research situation as well as the possible different approaches to the therapeutic influence of PCSK9 in the future.
authors.affiliation: BRAVE - Benefit for Research on Arterial Hypertension, Dyslipidemia and Vascular Risk and Education e.V., Gx00F6;ttingen, Germany.
authors.forename: Claas L
authors.initials: CL
authors.lastname: Neumann
authors.forename: Elke
authors.initials: E
authors.lastname: Schettler
authors.forename: Volker J J
authors.initials: VJ
authors.lastname: Schettler
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D001781:Blood Component Removal; D008078:Cholesterol, LDL / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017326:Clinical Trials, Phase III as Topic; D015870:Gene Expression; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D017270:Lipoprotein(a) / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017270:Lipoprotein(a); D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C577155:evolocumab; C571059:alirocumab