Role of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Diabetic Complications

Can J Physiol Pharmacol. 2023 Sep 25. doi: 10.1139/cjpp-2023-0223. Online ahead of print.ABSTRACTCardiovascular (CVD) complications have remained a major cause of death among patients with diabetes. Hence the need for effective therapeutics against diabetes-induced CVD complications. Since its discovery, proprotein convertase subtilisin/kexin type 9 (PCSK9) has been reported to be involved in the pathology of various cardiovascular diseases, with studies showing a positive association between plasma levels of PCSK9, hyperglycemia, and dyslipidemia. PCSK9 regulates lipid homeostasis by interacting with low-density lipoprotein receptor (LDLR) present in hepatocytes and subsequently induces LDLR degradation via receptor mediated endocytosis, thereby reducing low-density lipoprotein (LDL) uptake from circulation. In addition, PCSK9 also induces pro-inflammatory cytokine expression and apoptotic cell death in diabetic-CVD. Also, therapies designed to inhibit PCSK9 effectively reduces diabetic dyslipidemia with clinical studies reporting reduced cardiovascular events in patients with diabetes and no significant adverse effect on glycemic controls. In this review, we discuss the role of PCSK9 in the pathogenesis of diabetes-induced CVD and the potential mechanisms by which PCSK9 inhibition reduces cardiovascular events in diabetic patients.PMID:37748207 | DOI:10.1139/cjpp-2023-0223
Source: Canadian Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research