Role of endothelial let-7b in atherosclerosis

• Applicant: Maliheh Nazari Jahantigh, Ph.D.
• Subject Area: Cardiology, Angiology
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 387650765

Endothelial cells (EC) line the vascular system and regulate vascular tone, permeability, the blood coagulation system, and immune-inflammatory reactions. Disrupted blood flow in combination with hyperlipidemic conditions at arterial bifurcations induces microRNA-mediated EC dysfunction and diminishes endothelial regeneration, contributing to the formation of atherosclerotic lesions. However, the molecular mechanisms regulating the regenerative capacity of arterial ECs are currently not fully understood. Our preliminary results indicate that the miRNA let-7b in ECs reduces endothelial proliferation and increases atherosclerosis by targeting lncRNAs such as Lncpint. Therefore, I hypothesize that the suppression of lncRNAs by let-7b impairs the regeneration of dysfunctional ECs during atherosclerosis. To test this hypothesis, I aim to (i) assess the proatherogenic role of let-7b in EC dysfunction; (ii) identify let-7b RNA targets in arterial endothelial cells; and (iii) study the mechanism of function of let-7b targets in endothelial cells. I expect to identify a novel mechanism of endothelial regeneration during atherosclerosis characterized by lncRNA-induced EC proliferation. Thus, targeting endothelial let-7b-lncRNA interactions may provide a new therapeutic strategy to improve endothelial health and decrease atherosclerosis.

• DFG Programme: Research Grants