[Impacts and mechanisms of kruppel like factor 15 in pressure overload induced cardiac remodeling and angiogenesis in rats].

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

Methods: 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.

Results: 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.

Conclusion: 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.