MicroRNAs and the response to injury in atherosclerosis

Endothelial cells (ECs) at arterial branching points are physiologically subjected to chronic damage by disturbed blood flow, which triggers a vascular wound healing response. Additional damage by hyperlipid -aemia perturbs this delicate balance of en-dothelial injury and regeneration, and the progressive accumulation of noxious modified lipoproteins leads to macrophage death. Several miRNAs such as miR-92a and miR-712, which modulate EC proliferation and inflammation, are up-regulated by disturbed flow in ECs, and contribute to atherosclerosis. In addition, reduced endothelial levels of miR-126–5p limit the regenerative capacity of ECs, which becomes apparent by insufficient endothelial repair under hyperlipidemic stress. In macrophages, miR-342–5p induces the expression of miR-155 during the progression of atherosclerosis, which promotes inflammatory gene expression and inhibits efferocytosis by targeting Bcl6, thus contributing to necrotic core formation. Deciphering the complex cell- and context-specific effects of miRNAs during vascular wound healing appears essential for the development of miRNA-based therapies of atherosclerosis.