Comparative evaluation of torasemide and spironolactone on adverse cardiac remodeling in a rat model of dilated cardiomyopathy

In this study, we investigated the role of DNA methylation [5-methylcytosine (5mC)] and 5-hydroxymethylcytosine (5hmC), epigenetic modifications that regulate gene activity, in dilated cardiomyopathy (DCM). A MYBPC3 mutant mouse model of DCM was compared with wild type and used to profile genomic 5mC and 5hmC changes by Chip-seq, and gene expression levels were analyzed by RNA-seq. Both 5mC-altered genes (957) and 5hmC-altered genes (2,022) were identified in DCM hearts. Diverse gene ontology and KEGG pathways were enriched for DCM phenotypes, such as inflammation, tissue fibrosis, cell death, cardiac remodeling, cardiomyocyte growth, and differentiation, as well as sarcomere structure. Hierarchical clustering of mapped genes affected by 5mC and 5hmC clearly differentiated DCM from wild-type phenotype. Based on these data, we propose that genomewide 5mC and 5hmC contents may play a major role in DCM pathogenesis. NEW & NOTEWORTHY Our data demonstrate that development of dilated cardiomyopathy in mice is associated with significant epigenetic changes, specifically in intronic regions, which, when combined with gene expression profiling data, highlight key signaling pathways involved in pathological cardiac remodeling and heart contractile dysfunction.

Download Full-text

GW26-e2946 Increased expression of mitochondrial calreticulin in a rat model of dilated cardiomyopathy

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2015.06.1237 ◽

2015 ◽

Vol 66 (16) ◽

pp. C56

Author(s):

Ming Zhang ◽

Qiuhong Zhang ◽

Mingxia Chen

Keyword(s):

Dilated Cardiomyopathy ◽

Rat Model

Download Full-text

Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-β1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction

Cellular Physiology and Biochemistry ◽

10.1159/000487871 ◽

2018 ◽

Vol 45 (5) ◽

pp. 1797-1806 ◽

Cited By ~ 22

Author(s):

Anbang Han ◽

Yingdong Lu ◽

Qi Zheng ◽

Jian Zhang ◽

YiZhou Zhao ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Cardiac Function ◽

Signaling Pathways ◽

Rat Model ◽

Cardiac Remodeling ◽

Left Ventricular ◽

Protective Effects ◽

Tnf Α ◽

Tgf Β1

Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects. Methods: A rat model of acute myocardial infarction was induced by ligating the left anterior descending coronary artery. The rats were treated with QL (1.0 g/kg/day) for 4 weeks after surgery. Echocardiography and histology examination were performed to evaluate heart function and fibrosis, respectively. Protein levels of transforming growth factor-β1 (TGF-β1), phosphorylated Smad3 (p-Smad3), phosphorylated Smad7 (p-Smad7), collagen I (Col- I), alpha smooth muscle actin (a-SMA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor κB (NF-κB), and phosphorylated inhibitor of kappa B alpha (p-IκBα) were measured by western blot analysis. Results: QL treatment ameliorated adverse cardiac remodeling 8 weeks after AMI, including better preservation of cardiac function, decreased inflammation, and reduced fibrosis. In addition, QL treatment reduced Col-I, a-SMA, TGF-β1, and p-Smad3 expression levels but increased p-Smad7 levels in postmyocardial infarct rat hearts. QL administration also reduced the elevated levels of cardiac inflammation mediators, such as TNF-α and IL-6, as well as NF-κB and p-IκBα expression. Conclusions: QL therapy exerted protective effects against cardiac remodeling potentially by inhibiting TGF-β1/Smad3 and NF-κB signaling pathways, thereby preserving cardiac function, as well as reducing myocardial inflammation and fibrosis.

Download Full-text