Secreted miRNAs suppress atherogenesis

Abstract

Endothelial-vascular smooth muscle cell communication has a critical role in cardiovascular homeostasis and the pathogenesis of atherosclerosis. A study now demonstrates extracellular-vesicle-mediated transfer of the atheroprotective microRNAs miR-143/145 between endothelial and vascular smooth muscle cells, providing compelling evidence that intercellular transport of miRNAs can influence a pathological process, namely atherosclerosis.

Figure 1

Endothelial–VSMC communication through extracellular vesicles of atheroprotective miRNAs. (a) Under laminar flow conditions, endothelial KLF2 is upregulated. This leads to increased expression of miR-143/145 and transport of these miRNAs in extracellular vesicles to arterial VSMCs, where they repress specific target mRNAs involved in differentiation to the synthetic phenotype. As a result, the VSMCs are maintained in the contractile phenotype associated with normal arterial physiology and atheroprotection. (b) Under non-laminar or turbulent flow conditions, endothelial KLF2 is downregulated, leading to decreased expression of miR-143/145, decreased extracellular vesicle transport to VSMCs and de-repression of mRNAs involved in the synthetic phenotype. As a result, the VSMCs transition to the synthetic phenotype associated with atherosclerosis.