Smooth muscle cell FTO regulates contractile function

Am J Physiol Heart Circ Physiol. 2022 Oct 28. doi: 10.1152/ajpheart.00427.2022. Online ahead of print.ABSTRACTThe Fat mass and obesity gene (FTO) is a N6-methyladenosine RNA demethylase that was initially linked by GWAS studies to increased rates of obesity. Subsequent studies have revealed multiple mass-independent effects of the gene, including cardiac myocyte contractility. We created a mouse with a conditional and inducible smooth muscle cell deletion of Fto (Myh11 Cre + Ftofl/fl) and did not observe any changes in mouse body mass or mitochondrial metabolism. However, the mice had significantly decreased blood pressure (hypotensive) despite increased heart rate and sodium, and significantly increased plasma renin. Remarkably, the third order mesenteric arteries from these mice had almost no myogenic tone or capacity to constrict to smooth muscle depolarization or phenyleprhine. Microarray analysis from Fto-/- isolated smooth muscle cells demonstrated a significant decrease in serum response factor (Srf) and the downstream effectors Acta2, Myocd, and Tagln; this was confirmed in cultured human coronary arteries with FTO siRNA. We conclude Fto is an important component to the contractility of smooth muscle cells.PMID:36306211 | DOI:10.1152/ajpheart.00427.2022
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Source Type: research