Department of Cardiology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.
Department of Vascular Diseases, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.
Int J Mol Sci. 2023 Jan 19;24(3):1966. doi: 10.3390/ijms24031966.
Disturbances in lipid metabolism are among the most important risk factors for atherosclerotic cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key protein in lipid metabolism that is also involved in the production of inflammatory cytokines, endothelial dysfunction and aherosclerotic plaque development. Studies have shown a connection between PCSK9 and various indicators of inflammation. Signalling pathways that include PCSK9 play important role in the initiation and development of atherosclerotic lesions by inducing vascular inflammation. Studies so far have suggested that PCSK9 is associated with procoagulation, enhancing the development of atherosclerosis. Experimentally, it was also found that an increased concentration of PCSK9 significantly accelerated the apoptosis of endothelial cells and reduced endothelial function, which created conditions for the development of atherosclerosis. PCSK9 inhibitors can therefore improve clinical outcomes not only in a lipid-dependent manner, but also through lipid-independent pathways. The aim of our review was to shed light on the impact of PCSK9 on these factors, which are not directly related to low-density lipoprotein (LDL) cholesterol metabolism.
脂质代谢紊乱是动脉粥样硬化性心血管疾病最重要的危险因素之一。前蛋白转化酶枯草溶菌素/糜蛋白酶 9 型（PCSK9）是脂质代谢中的关键蛋白，也参与炎症细胞因子的产生、内皮功能障碍和动脉粥样硬化斑块的发展。研究表明，PCSK9 与各种炎症指标之间存在关联。包括 PCSK9 在内的信号通路通过诱导血管炎症，在动脉粥样硬化病变的发生和发展中发挥重要作用。迄今为止的研究表明，PCSK9 与促凝作用有关，可增强动脉粥样硬化的发展。实验还发现，PCSK9 浓度的增加显著加速了内皮细胞的凋亡并降低了内皮功能，为动脉粥样硬化的发展创造了条件。因此，PCSK9 抑制剂不仅可以通过依赖于脂质的方式，还可以通过非依赖于脂质的途径改善临床结局。我们的综述旨在阐明 PCSK9 对这些与低密度脂蛋白（LDL）胆固醇代谢无关的因素的影响。
