Objective Based on animal model of left ventricular pressure overload induced cardiac fibrosis,to investigate the specific role and molecular mechanism of KLF15 gene in this process.Methods To establish rat animal model of pressure overload induced cardiac hypertrophy by aortic coarctation under non artificial ventilation conditions,and then release the constriction,to observe the rat heart color Doppler images,myocardial interstitial fibrosis features and protein expression level changes of KLF15、Transforming growth factor-β (TGF-β) 、Connective tissue growth factor (CTGF)、Myocardin-related transcription factor A(MRTF-A) in overload-unload corresponding time points.Results We successfully completed aortic banding and debanding operations by use of SD rats without artificial ventilation.Through color Doppler echocardiography detection,from images to know:the effect of constriction and loosening is definite.The expression of collagen type Ⅰ,collagen type Ⅲ,TGF-β,CTGF,MRTF-A were significantly higher and myocardial hypertrophy was aggravated but the KLF15 protein expression level was significantly lower in pressure overloaded rats than in Sham rats(all P ＜ 0.05).All values were in an increasing tendency with the constrictive time prolonged (P ＜ 0.05).The response to unloading was opposite,the sooner to loose the better to the recovery to normal.The differences of indicators are very notable (P ＜ 0.05).Conclusion By feedback regulation TGF-β,KLF15 inhibited the effect of CTGF and MRTF-A,reducing myocardial interstitial fibrosis.

OBJECTIVETo explore the impact of kruppel like factor 15 (KLF15) on cardiac fibroblasts on angiogenesis in a pressure overload rat model.

METHODSPressure 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.

RESULTSThe 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.

CONCLUSIONOur 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.

Animals ; Aorta ; Aortic Valve Stenosis ; Down-Regulation ; Female ; Fibrosis ; Heart ; Kruppel-Like Transcription Factors ; metabolism ; Myocardium ; Neovascularization, Physiologic ; Rats ; Vascular Remodeling