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Content archived on 2024-06-18

Role of microRNAs 143 and 145 in cardiovascular physiology and disease: from bench to bedside

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Biomarkers for atherosclerosis

European researchers investigated how regulators of gene expression might affect the arteriosclerotic degeneration of blood vessel walls. Their findings, apart from facilitating prompt diagnosis, could have therapeutic relevance as well.

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Atherosclerosis is a condition associated with the thickening of blood vessel walls and alongside hypertension could lead to heart disease. Atherosclerotic plaque formation commences with lipid deposition followed by smooth muscle cell (SMC) migration and accumulation. The phenotypic switch from a non-proliferative to a migratory state seems to be governed by the differential expression of microRNAs (miRNAs), short RNAs implicated in gene expression regulation. The EU-funded FROM BENCH TO BEDSIDE (Role of microRNAs 143 and 145 in cardiovascular physiology and disease: From bench to bedside) project set out to investigate the role of miR-143 and miR-145 in occlusive vasculopathies. Using a combination of molecular biology, cellular biology, bioinformatic and proteomic techniques, researchers studied these miRNAs in vascular SMCs, pericytes and endothelial cells of atherosclerotic mouse models. Results unveiled a role for miR-143 and miR-145 in the communication between SMCs and endothelial cells. Moreover, the identification of a single nucleotide polymorphism present in the primary sequence of the human miR-143/145 cluster led scientists to speculate its influence on miRNA maturation. Most importantly, they found a correlation of this genetic variation with cardiac complications in a cohort of coronary artery disease patients. Considering that prompt diagnosis of atherosclerosis is difficult and occurs only after considerable arterial wall degeneration, biomarkers associated with this condition would be highly beneficial. The present study demonstrates a possible application of miRNAs as early vascular disease biomarkers that might improve the outcome of patients. Furthermore, the discovery of a miRNA regulatory mechanism behind atherosclerosis opens new roads for therapy.

Keywords

Biomarkers, atherosclerosis, gene expression, smooth muscle cell, miRNAs, miR-143, miR-145

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