Function, Role, and Clinical Application of MicroRNAs in Vascular Aging

Abstract

Vascular aging, a specific type of organic aging, is related to age-dependent changes in the vasculature, including atherosclerotic plaques, arterial stiffness, fibrosis, and increased intimal thickening. Vascular aging could influence the threshold, process, and severity of various cardiovascular diseases, thus making it one of the most important risk factors in the high mortality of cardiovascular diseases. As endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are the main cell biological basis of these pathology changes of the vasculature, the structure and function of ECs and VSMCs play a key role in vascular aging. MicroRNAs (miRNAs), small noncoding RNAs, have been shown to regulate the expression of multiple messenger RNAs (mRNAs) posttranscriptionally, contributing to many crucial aspects of cell biology. Recently, miRNAs with functions associated with aging or aging-related diseases have been studied. In this review, we will summarize the reported role of miRNAs in the process of vascular aging with special emphasis on EC and VSMC functions. In addition, the potential application of miRNAs to clinical practice for the diagnosis and treatment of cardiovascular diseases will also be discussed.

Figure 1

Network system of several important miRNAs regulating the function of ECs. The picture shows that SIRT1 is an important gene in the regulation of EC function. miR-34a, miR-217, miR-132, and let-7g are targets of SIRT1. Other miRNAs, such as miR-221/222, miR-126, and miR-21, participate in the function of ECs via targeting different genes. They can promote or inhibit the functions (senescence, apoptosis, proliferation, angiogenesis, and inflammation) of ECs. “—” indicates promotion effects; “—” denotes inhibition effects.

Figure 2

miRNAs that regulate phenotypic switching in VSMCs. The picture shows a variety of miRNAs that are involved in regulating the proliferation, migration, apoptosis, and differentiation of VSMCs. The red arrows indicate stimulatory effects, while the black arrows indicate inhibitory effects.