Open AccessUp‐regulation of alpha‐smooth muscle actin in cardiomyocytes from non‐hypertrophic and non‐failing transgenic mouse hearts expressing N‐terminal truncated cardiac troponin I
Author(s) -
Kern Stephanie,
Feng Han-Zhong,
Wei Hongguang,
Cala Steven,
Jin J.-P.
Publication year - 2014
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1016/j.fob.2013.11.002
Subject(s) - troponin i , medicine , contractility , genetically modified mouse , troponin , actin , myocyte , hypertrophic cardiomyopathy , transgene , sma* , myofibril , muscle hypertrophy , endocrinology , biology , cardiology , microbiology and biotechnology , biochemistry , mathematics , combinatorics , myocardial infarction , gene
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.