Yu Yang, Zou Shufan, Ma Jie, Chen Lin
Department of Cardiac Surgery, Xinqiao Hospital Affiliated to Third Military Medical University, Chongqing 400037, China.
Department of Cardiac Surgery, Xinqiao Hospital Affiliated to Third Military Medical University, Chongqing 400037, China. Email:
Zhonghua Xin Xue Guan Bing Za Zhi. 2015 Feb;43(2):162-6.
To explore the impact of kruppel like factor 15 (KLF15) on cardiac fibroblasts on angiogenesis in a pressure overload rat model.
Pressure overload was induced in female rats by aortic constriction for 3 and 6 weeks. After 6 weeks aortic banding, rats underwent aortic debanding for 3 or 6 weeks. Sham rats were observed for 3 and 6 weeks (n = 10 each). Cardiac function, myocardial pathological changes, interstitial angiogenesis and KLF15 expression during rat myocardial overloading-unloading process were determined. Cardiac fibroblasts and vascular endothelial cells were cultured in vitro in the absence or presence of KLF15-shRNA recombinant adenovirus and the regulation effect of KLF15 on vascular endothelial cells and angiogenesis was observed on a three-dimensional angiogenesis in vitro model.
The ascending aorta diameter, ejection fraction, fractional shortening, left ventricular systolic pressure and the KLF15 protein expression level were significantly lower but the left ventricular end-diastolic pressure was significantly higher in pressure overloaded rats than in Sham rats (all P < 0.01) after 6 weeks. At the same time, increased myocardial hypertrophy and fibrosis as well as reduced angiogenesis density were observed in pressure overloaded rats. These changes were significantly attenuated post aortic debanding. In vitro, KLF15-shRNA recombinant adenovirus transfection into cardiac fibroblasts significantly downregulated the protein expression of KLF15 compared with the control group (4 922 ± 430 vs. 7 034 ± 178, P < 0.01). The formation of tubular structure of vascular endothelial cells was shorter after KLF15-shRNA recombinant adenovirus transfection and the structure was incomplete when compared with the control group.
Our results suggest that upregulation of KLF15 expression in myocardial fibroblasts might promote vascular generation, alleviate the myocardial interstitial fibrosis and improve cardiac function in this pressure overload rat model.
探讨克勒普样因子15（KLF15）对压力超负荷大鼠模型中心脏成纤维细胞血管生成的影响。
通过主动脉缩窄法诱导雌性大鼠压力超负荷3周和6周。主动脉缩窄6周后，对大鼠进行主动脉解缚3周或6周。假手术大鼠观察3周和6周（每组n = 10）。测定大鼠心肌负荷-卸载过程中心脏功能、心肌病理变化、间质血管生成及KLF15表达。在有无KLF15-shRNA重组腺病毒的情况下体外培养心脏成纤维细胞和血管内皮细胞，并在三维体外血管生成模型上观察KLF15对血管内皮细胞和血管生成的调节作用。
6周后，压力超负荷大鼠的升主动脉直径、射血分数、缩短分数、左心室收缩压和KLF15蛋白表达水平显著低于假手术大鼠，但左心室舒张末期压力显著高于假手术大鼠（均P < 0.01）。同时，观察到压力超负荷大鼠心肌肥大和纤维化增加，血管生成密度降低。主动脉解缚后这些变化明显减轻。体外实验中，与对照组相比，将KLF15-shRNA重组腺病毒转染到心脏成纤维细胞中可显著下调KLF15蛋白表达（4 922 ± 430 vs. 7 034 ± 178，P < 0.01）。与对照组相比，KLF15-shRNA重组腺病毒转染后血管内皮细胞管状结构形成较短且结构不完整。
我们的结果表明，在该压力超负荷大鼠模型中，心肌成纤维细胞中KLF15表达上调可能促进血管生成，减轻心肌间质纤维化并改善心脏功能。
