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FEBS Open Bio. 2013 Nov 23;4:11-7. doi: 10.1016/j.fob.2013.11.002. eCollection 2013.

Up-regulation of alpha-smooth muscle actin in cardiomyocytes from non-hypertrophic and non-failing transgenic mouse hearts expressing N-terminal truncated cardiac troponin I.

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1
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.

Abstract

We previously reported that a restrictive N-terminal truncation of cardiac troponin I (cTnI-ND) is up-regulated in the heart in adaptation to hemodynamic stresses. Over-expression of cTnI-ND in the hearts of transgenic mice revealed functional benefits such as increased relaxation and myocardial compliance. In the present study, we investigated the subsequent effect on myocardial remodeling. The alpha-smooth muscle actin (α-SMA) isoform is normally expressed in differentiating cardiomyocytes and is a marker for myocardial hypertrophy in adult hearts. Our results show that in cTnI-ND transgenic mice of between 2 and 3 months of age (young adults), a significant level of α-SMA is expressed in the heart as compared with wild-type animals. Although blood vessel density was increased in the cTnI-ND heart, the mass of smooth muscle tissue did not correlate with the increased level of α-SMA. Instead, immunocytochemical staining and Western blotting of protein extracts from isolated cardiomyocytes identified cardiomyocytes as the source of increased α-SMA in cTnI-ND hearts. We further found that while a portion of the up-regulated α-SMA protein was incorporated into the sarcomeric thin filaments, the majority of SMA protein was found outside of myofibrils. This distribution pattern suggests dual functions for the up-regulated α-SMA as both a contractile component to affect contractility and as possible effector of early remodeling in non-hypertrophic, non-failing cTnI-ND hearts.

KEYWORDS:

Cardiac muscle remodeling; Cardiomyocyte; N-terminal truncation; TnI, troponin I; TnT, Troponin T; Transgenic mouse; Troponin I; cTnI, cardiac troponin I; cTnI-ND, N-terminal truncated cardiac troponin I; α-CA, alpha-cardiac actin; α-SKA, alpha-skeletal muscle actin; α-SMA; α-SMA, alpha-smooth muscle actin

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