Cardiometabolic diseases (CMD) (such as atherosclerosis, hypertension) are the primary cause of death and disability in the Western world. Although lifestyle programmes and therapeutic approaches have significantly reduced the socio-economic burden of CMD, a large number of events still cannot be avoided (residual risk). Neointimal hyperplasia is the principal pathogenic occurrence underlying atherosclerosis, restenosis. The common feature in these disorders is de novo tissue formation in the intimal layer due to inappropriate vascular smooth muscle cell (SMC) proliferation and migration. MicroRNAs (miRs) are short, non-coding RNAs that negatively regulate the proteins expression by binding to the 3’ UTR of target mRNAs. Bioinformatic analysis predicts that each miR may regulate hundreds of targets, suggesting that they might play roles in almost every biological process, including those of the cardiovascular system. Studies are beginning to unravel their fundamental importance in vessel biology. In this grant, we propose to study the role of 2 clustered miRs, miR-143 and -145, in vessel SMC and pericyte biology, and their possible application as biomarkers of vessel diseases and as a therapeutic tool for curing occlusive vasculopathies. These 2 miRs are part of the same bicistronic unit; we previously found that they are particularly expressed in the vasculature and are able to regulate vascular homeostasis and SMC migration and proliferation: thus, their modulation may have clinical implications in the pathogenesis of vessel disease. Previous data revealed that vascular stress is associated with down-regulation of these miRs in SMCs: their modulation was found to be responsible for SMC phenotypic switch from a contractile/non proliferative to a migratory/proliferative state. We intend, therefore, to characterize the role of these miRs in atherosclerosis development with a combination of molecular biology, cellular biology, bioinformatic and proteomic techniques.
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Funding SchemeMC-IRG - International Re-integration Grants (IRG)