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. 2016 Aug 1;111(3):204-16.
doi: 10.1093/cvr/cvw101. Epub 2016 May 20.

Endothelial deletion of protein tyrosine phosphatase-1B protects against pressure overload-induced heart failure in mice

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Endothelial deletion of protein tyrosine phosphatase-1B protects against pressure overload-induced heart failure in mice

Rajinikanth Gogiraju et al. Cardiovasc Res. .

Erratum in

  • Corrigendum.
    [No authors listed] [No authors listed] Cardiovasc Res. 2020 Jul 1;116(8):1541. doi: 10.1093/cvr/cvaa112. Cardiovasc Res. 2020. PMID: 32479588 No abstract available.

Abstract

Aims: Cardiac angiogenesis is an important determinant of heart failure. We examined the hypothesis that protein tyrosine phosphatase (PTP)-1B, a negative regulator of vascular endothelial growth factor (VEGF) receptor-2 activation, is causally involved in the cardiac microvasculature rarefaction during hypertrophy and that deletion of PTP1B in endothelial cells prevents the development of heart failure.

Methods and results: Cardiac hypertrophy was induced by transverse aortic constriction (TAC) in mice with endothelial-specific deletion of PTP1B (End.PTP1B-KO) and controls (End.PTP1B-WT). Survival up to 20 weeks after TAC was significantly improved in mice lacking endothelial PTP1B. Serial echocardiography revealed a better systolic pump function, less pronounced cardiac hypertrophy, and left ventricular dilation compared with End.PTP1B-WT controls. Histologically, banded hearts from End.PTP1B-KO mice exhibited increased numbers of PCNA-positive, proliferating endothelial cells resulting in preserved cardiac capillary density and improved perfusion as well as reduced hypoxia, apoptotic cell death, and fibrosis. Increased relative VEGFR2 and ERK1/2 phosphorylation and greater eNOS expression were present in the hearts of End.PTP1B-KO mice. The absence of PTP1B in endothelial cells also promoted neovascularization following peripheral ischaemia, and bone marrow transplantation excluded a major contribution of Tie2-positive haematopoietic cells to the improved angiogenesis in End.PTP1B-KO mice. Increased expression of caveolin-1 as well as reduced NADPH oxidase-4 expression, ROS generation and TGFβ signalling were observed and may have mediated the cardioprotective effects of endothelial PTP1B deletion.

Conclusions: Endothelial PTP1B deletion improves cardiac VEGF signalling and angiogenesis and protects against chronic afterload-induced heart failure. PTP1B may represent a useful target to preserve cardiac function during hypertrophy.

Keywords: Angiogenesis; Fibrosis; Heart failure; Hypertrophy; PTP1B.

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