Natarelli L, Schober A
Andreas Schober, MD, Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Pettenkoferstr. 9, 80336 Munich, Germany, Tel. +49/(0)89/44 00 54-530; Fax -740, E-mail:
Hamostaseologie. 2015;35(2):142-50. doi: 10.5482/HAMO-14-10-0051. Epub 2015 Jan 23.
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 hyperlipidaemia perturbs this delicate balance of endothelial 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.
