Mieczysław Dutka, Karolina Zimmer, Michał Ćwiertnia, Tomasz Ilczak, Rafał Bobiński
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引用次数: 0
Abstract
Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a protein that regulates low-density lipoprotein (LDL) cholesterol metabolism by binding to the hepatic LDL receptor (LDLR), ultimately leading to its lysosomal degradation and an increase in LDL cholesterol (LDLc) levels. Treatment strategies have been developed based on blocking PCSK9 with specific antibodies (alirocumab, evolocumab) and on blocking its production with small regulatory RNA (siRNA) (inclisiran). Clinical trials evaluating these drugs have confirmed their high efficacy in reducing serum LDLc levels and improving the prognosis in patients with atherosclerotic cardiovascular diseases. Most studies have focused on the action of PCSK9 on LDLRs and the subsequent increase in LDLc concentrations. Increasing evidence suggests that the adverse cardiovascular effects of PCSK9, particularly its atherosclerotic effects on the vascular wall, may also result from mechanisms independent of its effects on lipid metabolism. PCSK9 induces the expression of pro-inflammatory cytokines contributing to inflammation within the vascular wall and promotes apoptosis, pyroptosis, and ferroptosis of cardiomyocytes and is thus involved in the development and progression of heart failure. The elimination of PCSK9 may, therefore, not only be a treatment for hypercholesterolaemia but also for atherosclerosis and other cardiovascular diseases. The mechanisms of action of PCSK9 in the cardiovascular system are not yet fully understood. This article reviews the current understanding of the mechanisms of PCSK9 action in the cardiovascular system and its contribution to cardiovascular diseases. Knowledge of these mechanisms may contribute to the wider use of PCSK9 inhibitors in the treatment of cardiovascular diseases.
期刊介绍:
Heart Failure Reviews is an international journal which develops links between basic scientists and clinical investigators, creating a unique, interdisciplinary dialogue focused on heart failure, its pathogenesis and treatment. The journal accordingly publishes papers in both basic and clinical research fields. Topics covered include clinical and surgical approaches to therapy, basic pharmacology, biochemistry, molecular biology, pathology, and electrophysiology.
The reviews are comprehensive, expanding the reader''s knowledge base and awareness of current research and new findings in this rapidly growing field of cardiovascular medicine. All reviews are thoroughly peer-reviewed before publication.