PCSK9 degrades LDL receptors and subsequently increases serum LDL-cholesterol. Clinical trials show that inhibition of PCSK9 efficiently lowers LDL-cholesterol levels and reduces cardiovascular events. PCSK9 inhibitors also reduce the extent of atherosclerosis. Recent studies show that PCSK9 is secreted by vascular endothelial cells, smooth muscle cells and macrophages. PCSK9 induces secretion of pro-inflammatory cytokines in macrophages, liver cells, and in a variety of tissues. PCSK9 regulates TLR4 expression and NF-κB activation as well as development of apoptosis and autophagy. PCSK9 also interacts with oxidized-LDL receptor-1 (LOX-1) in a mutually facilitative fashion. These observations suggest that PCSK9 is inter-twined with inflammation with implications in atherosclerosis and its major consequence - myocardial ischemia. This relationship provides a basis for the use of PCSK9 inhibitors in prevention of atherosclerosis and related clinical events.

中文翻译：

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PCSK9 和炎症：剪切应力、促炎细胞因子和 LOX-1 4 的作用。

PCSK9 降解低密度脂蛋白受体，随后增加血清低密度脂蛋白胆固醇。临床试验表明，抑制 PCSK9 可有效降低低密度脂蛋白胆固醇水平并减少心血管事件。PCSK9 抑制剂还可以降低动脉粥样硬化的程度。最近的研究表明，PCSK9 由血管内皮细胞、平滑肌细胞和巨噬细胞分泌。PCSK9 诱导巨噬细胞、肝细胞和各种组织中促炎细胞因子的分泌。PCSK9 调节 TLR4 表达和 NF-κB 激活以及细胞凋亡和自噬的发展。PCSK9 还以相互促进的方式与氧化 LDL 受体 1 (LOX-1) 相互作用。这些观察结果表明 PCSK9 与炎症交织在一起，对动脉粥样硬化及其主要后果 - 心肌缺血有影响。