Role of miR-140-5p in vascular aging and arterial stiffening: a review of potential mechanisms

Abstract

Vascular aging is characterized by progressive endothelial dysfunction, arterial stiffening, and structural remodeling of the vascular wall, which are processes that precede overt cardiovascular disease and predict adverse outcomes independently. MicroRNAs have emerged as key post-transcriptional regulators linking cellular aging mechanisms to clinically measurable vascular phenotypes and their attenuation. Among them, miR-140-5p has gained attention for its role in maintaining vascular homeostasis and modulating aging-related vascular dysfunction. Experimental evidence indicates that miR-140-5p expression decreases with age and vascular stress due to epigenetic modifications, including promoter hyper-methylation and reduced miRNA biogenesis capacity, contributing to endothelial senescence, senescence-associated secretory phenotype (SASP), impaired nitric oxide bioavailability, and chronic low-grade inflammation. At the medial layer, reduced miR-140-5p favors vascular smooth muscle cell phenotypic switching and extracellular matrix imbalance, promoting arterial stiffening. These molecular alterations provide a mechanistic basis linking miR-140-5p dysregulation to established clinical indices of vascular aging, including reduced flow-mediated dilation and increased pulse wave velocity. This review synthesizes current evidence on the biological role of miR-140-5p in vascular aging, integrates microRNA molecular mechanisms with functional and structural vascular metrics, and discusses its potential as a biomarker and therapeutic target. Understanding the role of miR-140-5p may support strategies aimed at preserving vascular resilience and delaying age-related cardiovascular risk.
Keywords: MicroRNA, vascular aging, endothelial dysfunction, arterial stiffness, pulse wave velocity