Author + information
- Zheng Jia1,2,3,4,5,
- Qian Liu1,2,4,
- Zhengjiang Xing1,2,3,4,
- Jie Wei1,2,3,4,
- Honglin Zou1,2,3,4 and
- Li Yang1,2,4
To investigate the association between cardiac fibrosis and expression of Klotho, Collagen I and Collagen III mRNA in myocardial of rats with chronic heart failure, and explore the mechanism underlying Klotho-mediated cardioprotection. We determined whether reduce myocardial remodeling via adjusting the expression of Klotho, Collagen I and Collagen III in a rat model of chronic heart failure.
Male Sprague-Dawley rats (250-300g) were established to chronic heart failure model by continuous intraperitoneal injection of isoproterenol and sham model with saline. Cardiac weigh/body weigh index (CW/BW) was calculated from heart specimens. Hematoxylin Eosin and Masson staining were observed to myocardial pathological changes and myocardial fibrosis. Realtime-PCR was used to detect the expression of Klotho, Collagen I and Collagen III in the myocardium of models. Cardiac function was evaluated by echocardiography. Then, we investigate the association between cardiac fibrosis and expression of Klotho, Collagen I and Collagen III mRNA by statistical analysis. Moreover, Klotho-mediated cardioprotection such as reduce myocardial remodeling proved by the study.
The index of CW/BW in the CHF group was (6.02±0.31)g×1000/g significantly higher than that in sham group (4.09±0.24)g×1000/g, (P<0.01). The ejection fraction in sham model (69.78%±4.06) was significantly higher than that in CHF model (38.97%±2.52) (P<0.01). However, cardiomyocyte hypertrophy and necrosis, myocardial fiber rupture, myocardial interstitial fibrosis scar tissue formation, myocardial tissue structure disorder, the degree of myocardial fibrosis significantly higher in CHF model according to HE and Masson staining. The collagen volume fraction (CVF%) (55.387%±3.63) in CHF group significantly higher than that in sham group (0.301%±0.09) (P<0.01). Realtime-PCR results showed: Klotho mRNA relative expression decreased in CHF group (0.791±0.143) than that in sham group (1.9033±0.51) (P<0.05). Collagen I and Collagen III mRNA in CHF group (2.116±0.968) (2.678±1.176) highly expressed than that in sham group (0.033±0.01) (0.0833±0.046) (both P<0.05). Collagen I and Collagen III were showing a close negatively correlation with Klotho in CHF model’s myocardial (r=-0.586, P<0.05; r=-0.549, P<0.05).
1. Continuous intraperitoneal injection of isproterenol can construct a stable rat model of chronic heart failure. 2. In the process of myocardial remodeling, we are infer to the mechanism underlying of cardioprotection by up-regulated expression of Klotho and down-regulated expression of Collagen I and Collagen III. 3. The expression of Klotho mRNA showing independent and significantly negative correlation with Collagen I and Collagen III mRNA in the myocardium of chronic heart failure.