KLF15 is a protective regulatory factor of heart failure induced by pressure overload.

Abstract

The aim of the present study was to investigate the protective effect of Kruppel‑like factor 15 (KLF15) overexpression on heart failure (HF) induced by left ventricular (LV) pressure overload in mice. Wild‑type (WT) mice and cardiac‑specific KLF15‑overexpressed transgenic (TG) mice were selected as research subjects, and an LV pressure overload model was constructed by ascending aortic constriction surgery. Changes in cardiac morphology and function, and ultrastructure and molecular expression were observed via M‑mode echocardiography, histological and immunohistochemical staining, ELISA and western blotting at 2 and 6 weeks of LV overload. WT and TG mice subjected to 2 weeks of overload displayed adaptive LV hypertrophy characterized by ventricular thickness, cardiomyocyte size, ejection fraction and fractional shortening of heart‑lung weight ratio and KLF15, and increases in vascular endothelial growth factor (VEGF) expression without other pathological changes. WT mice subjected to 6 weeks of overload displayed enlargement of the LV chamber, severe interstitial remodeling, and HW/LW, cardiac capillary and heart function decline, accompanied by downregulated expression of KLF15 and VEGF, and upregulated expression of connective tissue growth factor, phosphorylated p38 (p‑p38) and phosphorylated Smad3 (p‑Smad3). In contrast, TG mice exhibited improved resistance to 6 weeks of overload and a slighter molecular expression response compared with WT mice. KLF15 was revealed to be a critical factor regulating the expression of CTGF, VEGF, p‑p38 and p‑Smad3, and could alleviate the progression from adaptive LV hypertrophy to decompensatory cardiac insufficiency.

• Authors: Shu-Fan Zou, Yang Yu, Yan Peng, Ying-Bin Xiao, Zhao Jian, Yun-Han Jiang, Sai Chen, Fu-Qin Tang, Lin Chen
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 21 Issue 3 Pg. 1336-1345 (03 2020) ISSN: 1791-3004 [Electronic] Greece
• PMID: 31922214 (Publication Type: Journal Article)

Chemical References

• Klf15 protein, mouse
• Kruppel-Like Transcription Factors

Topics

• Animals
• Blood Pressure
• Disease Models, Animal
• Heart Failure (genetics, metabolism, physiopathology, prevention & control)
• Kruppel-Like Transcription Factors (genetics, metabolism)
• Mice
• Mice, Transgenic