MicroRNA-663 (miR-663) is reduced in the plasma and pulmonary vessels of patients with pulmonary arterial hypertension (PAH), making it a potential biomarker of the disease, according to a study by Chinese researchers.
Moreover, miR-663 decreases pulmonary artery smooth muscle cells proliferation, a hallmark of PAH, and prevents pulmonary vascular remodeling and right ventricular hypertrophy by targeting TGF-β1/smad2/3 signaling.
“These findings suggest that miR-663 may represent as an attractive approach for the diagnosis and treatment for PAH,” wrote Pan Li and the co-authors of the study that appeared in the Journal of Molecular and Cellular Cardiology.
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Recent studies have suggested that miR-663 could be a potent modulator for tumorigenesis and atherosclerosis. Increasing evidence also suggests that miRNAs participate in PAH pathogenesis and right ventricular hypertrophy.
In order to investigate the potential role of miR-663 in pulmonary vascular remodeling, a team of researchers assessed its expression in pulmonary artery smooth muscle cells. They found that miR-663 was highly expressed in normal human pulmonary artery smooth muscle cells but that its expression was dramatically reduced in patients with PAH.
When they transfected cells grown in culture with miR-663, the researchers found that this mimicked significantly inhibited platelet-derived growth factor-induced pulmonary artery smooth muscle cells proliferation and migration. On the contrary, knocking down the expression of miR-663 enhanced these processes.
The researchers also showed that miR-663 directly targets the 3’UTR of TGF-β1 and that it decreases platelet-derived growth factor-induced TGF-β1 expression and secretion. This, in turn, suppressed the downstream smad2/3 phosphorylation and collagen I expression.
“miR-663 targets TGF-β1/smad2/3 signaling and inhibits pulmonary arterial remodeling,” the researchers stated.
As a final experiment, the team intrathecally administered miR-663 in a rat model of PAH and showed this was able to inhibit the development of pulmonary vascular remodeling and right ventricular hypertrophy, suggesting that it may be a therapeutic target for PAH.
Li P, Song J, Du H, et al. MicroRNA-663 prevents monocrotaline-induced pulmonary arterial hypertension by targeting TGF-β1/smad2/3 signaling. J Mol Cell Cardiol. 2021;30:S0022-2828(21)00151-6. doi:10.1016/j.yjmcc.2021.07.010