Cardiac transcriptome profiles of S.LEW congenic strain compared with the hypertensive Dahl S rat

Despite inheritance of hypertension in families, identifying genetic mechanisms predisposing individuals to hypertension has remained challenging. The effects of single genes contributing to the development of hypertension may not be readily detected in individuals whose genomes also contain other genetic factors that resist hypertension. By using a highly permissive rat genome for inherited hypertension, we demonstrate that increased expression of one such gene, Rififylin (Rffl), is a novel inherited risk factor for hypertension and increased mortality. Animals overexpressing Rffl demonstrated delayed endocytic recycling, accumulated polyubiquitinated proteins, increased beats/min of neonatal cardiomyocytes, had shorter QT-intervals and developed salt-insensitive hypertension very early in their life (50-52 days). Thus, the discovery of a physiological link between overexpression of rififylin and the development of hypertension constitutes a novel mechanism that could be targeted for rectifying normal QT-interval and preventing hypertension.

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Gopalakrishnan K, Morgan EE, Yerga-Woolwine S, Farms P, Kumarasamy S, Kalinoski A, Liu X, Wu J, Liu L, Joe B