Fig. 9.

Schematic of the role of miR-30d/e in microvascular dysfunction in diabetes. Type 2 Diabetes (T2D) promotes microvascular dysfunction in the heart. In a mouse db/db model of T2D, microvascular rarefaction precedes echocardiographic evidence of diastolic dysfunction. The up-regulation of miR-30d/e in the endothelium of the heart is associated with induction of senescence-like pathways. MiR-30d/e can be secreted by the endothelium in extracellular vesicles (EVs) and detected in the circulation, and may serve as an early circulating biomarker of microvascular dysfunction. In the endothelium, miR-30d/e target a number of genes involved in fatty acid biosynthesis and in turn enhance β-oxidation of exogenous fatty acids. Over-expression of miR-30e results in oxidative stress, DNA damage and decreased levels of eNOS, which may contribute to microvascular dysfunction and rarefaction, ultimately contributing to diastolic dysfunction. The schematic was generated using Biorender