Calponin1 inhibits dilated cardiomyopathy development in mice through the εPKC pathway

• Published in: International journal of cardiology Vol. 173; no. 2; pp. 146 - 153
• Main Authors: Lu, Dan, Zhang, Li, Bao, Dan, Lu, Yingdong, Zhang, Xu, Liu, Ning, Ge, Wenping, Gao, Xiang, Li, Hongliang, Zhang, Lianfeng
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.05.2014; Elsevier
• Subjects: Animals; Biological and medical sciences; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Calponin1; Calponins; Cardiology. Vascular system; Cardiomyopathy, Dilated - genetics; Cardiomyopathy, Dilated - metabolism; Cardiomyopathy, Dilated - prevention & control; Cardiovascular; Dilated cardiomyopathy (DCM); Disease Models, Animal; Epsilon isoform of protein kinase C (εPKC); Heart; Heart failure (HF); Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; MAP Kinase Signaling System - physiology; Medical sciences; Mice, Inbred C57BL; Mice, Transgenic; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Myocarditis. Cardiomyopathies; Phenotype; Protein Kinase C-epsilon - metabolism; Survival Rate; TOR Serine-Threonine Kinases - metabolism; Transgenes - physiology; Transgenic mice; Epsilon isoform of protein kinase C (εPKC); Calponin1; Dilated cardiomyopathy (DCM); Heart failure (HF); Transgenic mice; Heart failure; Protein kinase C; Enzyme; Transferases; Rodentia; Cardiovascular disease; Myocardial disease; Vertebrata; Mammalia; Congestive hypertrophic cardiomyopathy; Mouse; Dilated cardiomyopathy; Heart disease; Animal; Development; Cardiology
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2014.02.032

Abstract Background Calponin1 (CNN1) is involved in the regulation of smooth muscle contraction in physiological situation and it also expresses abnormally in a variety of pathological situations. We found that the expression of CNN1 decreased significantly in the heart tissue of a cTnTR141W transgenic dilated cardiomyopathy (DCM) mouse model and an adriamycin (ADR)-induced DCM mouse model, suggesting that CNN1 is involved in the pathogenesis of DCM. However, the role of CNN1 on cardiac function, especially on pathogenesis of DCM, has not been clarified. In this study, we tested whether rescued expression of CNN1 could prevent the development of DCM and investigated its possible mechanisms. Methods and results The DCM phenotypes were significantly improved with the transgenic expression of CNN1 in the cTnTR141W × CNN1 double transgenic (DTG) mice, which was demonstrated by the survival, cardiac geometry and function analyses, as well as microstructural and ultrastructural observations based on echocardiography and histology examination. The expression of CNN1 could also resist the cardiac geometry breakage and dysfunction in the ADR-induced DCM mice model. Meanwhile, the epsilon isoform of protein kinase C (εPKC) activator and inhibitor could reverse the activation of εPKC/ERK/mTOR pathway and DCM phenotypes in the cTnTR141W and cTnTR141W × CNN1 double transgenic (DTG) mice. Conclusions εPKC/ERK/mTOR pathway activation induced by the rescued expression of CNN1 contributed to the improvement of cardiac dysfunction and pathological changes observed in the DTG mice. CNN1 could be a therapeutic target to prevent the development of DCM and heart failure (HF).