Further LDL cholesterol lowering through targeting PCSK9 for coronary artery disease.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that belongs to the proprotein convertase family. PCSK9 is synthesized as a zymogen and its prodomain is cleaved by its own catalytic activity. The cleaved prodomain forms a protein complex with the rest of the PCSK9 carboxyl terminus within the endoplasmic reticulum and is secreted. Secreted PCSK9 has been shown to be able to reduce low-density lipoprotein receptor (LDLR) levels in vitro and in vivo. Thus PCSK9 has emerged as an important player modulating LDLR levels and plasma LDL cholesterol. Furthermore, PCSK9 deficiency leads to significantly lowered LDL cholesterol levels in humans and provides dramatic protection against coronary heart disease. We review here the current understanding of PCSK9 and its potential as a therapeutic target through which to reduce LDL cholesterol for prevention and treatment of coronary heart disease.
Cao
Guoqing
G
Lilly Research Laboratories, Indianapolis, IN 46285, USA. Guoqing_cao@lilly.com
Qian
Yue-Wei
YW
Kowala
Mark C
MC
Konrad
Robert J
RJ
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy*; D015316:Genetic Therapy; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D034741:RNA, Small Interfering / Q000627:therapeutic use; D011973:Receptors, LDL / Q000187:drug effects; D012697:Serine Endopeptidases / Q000187:drug effects* / Q000235:genetics*
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases