The maladaptation of endothelial cells to disturbed flow at arterial bifurcations increases permeability for lipoproteins. Additional injury by chemically modified lipoproteins disrupts the continuous repair of maladapted endothelial cells and triggers intimal macrophage accumulation. Macrophages remove modified lipoproteins from the extracellular space until the cholesterol overload leads to macrophage death and insufficient efferocytosis. This macrophage failure promotes the progression to advanced lesions by formation of a lipid-rich necrotic core, which may rupture and cause myocardial infarction and stroke. In this article, we summarize the fundamental roles of microRNAs (miRNAs) in the regulation of endothelial maladaptation and macrophage failure during atherosclerosis. We describe how miRNAs coordinate the mutual interaction between chronic endothelial repair and endothelial senescence and mechanistically link the regulation of macrophage cholesterol homeostasis with defective efferocytosis. Lastly, we discuss how miRNAs may challenge and extend current theories about atherosclerosis.

中文翻译：

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MicroRNA在动脉粥样硬化中的机制。

内皮细胞适应于动脉分叉处的血流不畅会增加脂蛋白的通透性。化学修饰的脂蛋白造成的额外损伤破坏了适应不良的内皮细胞的连续修复，并触发了内膜巨噬细胞的积累。巨噬细胞从细胞外空间去除修饰的脂蛋白，直到胆固醇超载导致巨噬细胞死亡和不足的胞吞作用。这种巨噬细胞衰竭通过形成富含脂质的坏死核心来促进进展为晚期病变，所述坏死核心可能破裂并引起心肌梗塞和中风。在本文中，我们总结了微小RNA（miRNA）在动脉粥样硬化期间内皮适应不良和巨噬细胞衰竭调控中的基本作用。我们描述了miRNA如何协调慢性内皮修复和内皮衰老之间的相互相互作用，以及如何将巨噬细胞胆固醇稳态调节与缺陷性红细胞增多症联系起来。最后，我们讨论了miRNA如何挑战和扩展有关动脉粥样硬化的最新理论。