Cardiac-specific inactivation of Prdm16 effects cardiac conduction abnormalities and cardiomyopathy-associated phenotypes.

Cardiac-specific inactivation of Prdm16 effects cardiac conduction abnormalities and cardiomyopathy-associated phenotypes. Am J Physiol Heart Circ Physiol. 2020 Feb 21;: Authors: Nam JM, Lim JE, Ha TW, Oh B, Kang JO Abstract A variant in the PRDM16 locus has been correlated with QRS duration in an electrocardiogram genomewide association study, and the deletion of PRDM16 has been implicated as a causal factor of the dilated cardiomyopathy that is linked to 1p36 deletion syndrome. We aimed to determine how a null mutation of Prdm16 affects cardiac function and study the underlying mechanism of the resulting phenotype in an appropriate mouse model. We used cardiac-specific Prdm16 conditional knockout mice to examine cardiac function by electrocardiography. QRS duration and QTc interval increased significantly in cardiac-specific Prdm16 knockout animals compared with wild-type mice. Further, we assessed cardiomyopathy-associated features by trichrome staining, densitometry, and hydroxyproline assay. Prdm16-null hearts showed greater fibrosis and cardiomyocyte hypertrophy. By quantitative real-time PCR, Prdm16-null hearts upregulated extracellular matrix-related genes (Ctgf, Timp1) and a-smooth muscle actin (Acta2), a myofibroblast marker. Moreover, TGF-b signaling was activated in Prdm16-null hearts, as evidenced by increased Tgfb1-3 transcript levels and phosphorylated Smad2. However, the inhibition of TGF-b receptor did not reverse th...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research