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. Issue 1 (23rd November 2013)

• Record Type: Journal Article
• Authors: Kern, Stephanie; Feng, Han-Zhong; Wei, Hongguang; Cala, Steven; Jin, J.-P.
• Is Part Of: FEBS open bio. Volume 4:Issue 1(2014)
• Page Start: 11
• Page End: 17
• Publication Date: 2013-11-23
• Subjects: Troponin I -- N-terminal truncation -- α-SMA -- Cardiac muscle remodeling -- Cardiomyocyte -- Transgenic mouse; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.fob.2013.11.002
• Languages: English
• ISSNs: 2211-5463

Abstract

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. Abstract : N‐terminal truncated cardiac troponin I (cTnI‐ND) upregulates α‐smooth muscle actin. This myocardial hypertrophy marker is expressed early in cardiomyocytes. Increased relaxation by cTnI‐ND has a potent effect on myocardial remodeling. The majority of α‐smooth muscle actin was found outside of myofibrils.