医学
发病机制
转基因
心功能曲线
心力衰竭
转基因小鼠
激活剂(遗传学)
扩张型心肌病
MAPK/ERK通路
表型
蛋白激酶C
心肌病
基因亚型
内科学
内分泌学
病理
细胞生物学
信号转导
受体
生物
基因
生物化学
作者
Dongfang Lu,Li Zhang,Dan Bao,Yingdong Lu,Xu Zhou,Ning Liu,Wenping Ge,Xiang Gao,Hongliang Li,Lianfeng Zhang
标识
DOI:10.1016/j.ijcard.2014.02.032
摘要
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).
科研通智能强力驱动
Strongly Powered by AbleSci AI