KLF15 is a positive regulatory factor in the process of myocardial remodeling and angiogenesis induced by pressure overload

Objectives: To elucidate the role of KLF15 on cardiac fibroblast in the dynamic angiogenesis in pressureoverload cardiac remodeling. Methods: Aortic banding was performed in rats to induce pressure-overload and cardiac hypertrophy. Part of the animals has their aorta constriction removed 3 or 6 weeks after the banding surgery. Cardiac function by echocardiography, cardiac tissue morphology and fibrosis, interstitial angiogenesis and KLF15 expression were measured. The effect of KLF15 on cardiac fibroblasts and vascular endothelial cells was determined in vitro using an over-expression system by KLF15 recombinant adenovirus to investigate the role of KLF15 in angiogenesis. Results: Pressure overload led to cardiac dysfunction, myocardial hypertrophy and fibrosis, accompanied with decreased capillary density. These phenotypes were associated with decreased cardiac expression level of KLF5. All cardiac dysfunction and hypertrophy phenotypes were slowed down or reversed by de-banding the constriction at an early stage (3 weeks after banding) together with a normalized cardiac KLF5 level, and partially reversed at a late stage (6 weeks after banding). In vitro over-expressing KLF15 in cardiac fibroblast promoted the formation of budding and tubular structure of endothelial cells in a three-dimensional co-cultures system, providing a potential causational relation between KLF15 and angiogenesis. Conclusion: Pressure-overload induced cardiac hypertrophy led to enhanced vascular angiogenesis which was possibly regulated by KLF15 base on both in vivo and in vitro data. Pressure-overload alleviation resulted in improved cardiac function, and partial reversal of fibrosis and angiogenesis with reversed KLF15 levels.