Targeting proprotein convertase subtilisin/kexin type 9 in mice and monkeys
نویسندگان
چکیده
منابع مشابه
Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis.
Hypercholesterolemia is a major risk factor for cardiovascular diseases, increasing the incidence of myocardial infarction and death. Statin-induced lowering of low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular morbidity and mortality. However, many individuals treated with statins do not achieve their target levels of LDL-C, and thus, LDL-associated residual risk remains. Gain...
متن کاملGene inactivation of proprotein convertase subtilisin/kexin type 9 reduces atherosclerosis in mice.
BACKGROUND The proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes independently of its enzymatic activity the degradation of the low-density lipoprotein (LDL) receptor. PCSK9 gain of function in humans leads to autosomal dominant hypercholesterolemia, whereas the absence of functional PCSK9 results in ≈7-fold lower levels of LDL cholesterol. This suggests that lowering PCSK9 may pro...
متن کاملProprotein convertase subtilisin kexin type 9 null mice are protected from postprandial triglyceridemia.
OBJECTIVES Proprotein convertase subtilisin kexin type 9 (PCSK9) is a natural inhibitor of the low-density lipoprotein receptor, and its deficiency in humans results in low plasma LDL-cholesterol and protection against cardiovascular disease. We explored whether PCSK9 expression impacts postprandial triglyceridemia, another important cardiovascular risk factor. METHODS AND RESULTS Real-time P...
متن کاملLipid-lowering interventions targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): an emerging chapter in lipid-lowering therapy
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that is mainly expressed in the liver but can also be found in the intestine and kidneys. PCSK9 promotes the degradation of low density lipoprotein receptors (LDLR) by reducing their recycling and targeting the receptors for lysosomal destruction, thereby decreasing the rate of removal of LDL-cholesterol from the circula...
متن کاملA proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) by interacting with the LDL receptor (LDLR) and is an attractive therapeutic target for LDL-C lowering. We have generated a neutralizing anti-PCSK9 antibody, mAb1, that binds to an epitope on PCSK9 adjacent to the region required for LDLR interaction. In vitro, mAb1 inhibits PCSK9 binding to the LDLR a...
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ژورنال
عنوان ژورنال: Current Opinion in Lipidology
سال: 2019
ISSN: 0957-9672
DOI: 10.1097/mol.0000000000000583