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

• Published in: FEBS open bio 2014-01, Vol.4 (1), p.11-17
• Main Authors: Kern, Stephanie, Feng, Han-Zhong, Wei, Hongguang, Cala, Steven, Jin, J.-P.
• Format: Article
• Language: English
• Subjects: Actin; Adaptation; Calcium-binding protein; Cardiac muscle remodeling; Cardiomyocyte; Cardiomyocytes; Filaments; Gene expression; Heart failure; Hypertrophy; Kinases; Muscle contraction; Musculoskeletal system; Myofibrils; N-terminal truncation; Proteins; Smooth muscle; Software; Transgenic animals; Transgenic mice; Transgenic mouse; Troponin; Troponin I; Western blotting; Young adults; α-SMA
• ISSN: 2211-5463; 2211-5463
• DOI: 10.1016/j.fob.2013.11.002

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. •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.