Endothelial deletion of protein tyrosine phosphatase-1B protects against pressure overload-induced heart failure in mice
Authors: Astrid Hubert
Magdalena L Bochenek
Katrin Schäfer
Gerd Hasenfuss
Thomas Münzel
Marco R Schroeter
Rajinikanth Gogiraju
Journal: Cardiovascular Research (2016)
Discipline: CLINICAL MEDICINE
Keywords: Angiogenesis; Fibrosis; Heart failure; Hypertrophy; PTP1B.
Affiliations: Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany., Center for Cardiology, Department of Cardiology I, University Medical Center Mainz, Mainz, Germany Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany., Center for Cardiology, Department of Cardiology I, University Medical Center Mainz, Mainz, Germany., Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany Center for Cardiology, Department of Cardiology I, University Medical Center Mainz, Mainz, Germany .

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. 

Retracted: No

PubPeer comments:
 Figure 7A. 2 Sham images in 2nd row appear to be the same. Marked in green. Caption follows. *** ![file] *** ![file] , 
 More image similarities between Lectin stain TAC 20wks (Figure 2A) PCNA stain TAC 20wks (Figure 5A). ![file] , 
 **Corrigendum: Cardiovascular Research, cvaa112, Published: 01 June 2020**  The authors regret that that in Figure 7A the image showing p-Smad2 in the End.PTP1B-KO sham group (third column, second row) is a duplicate of findings in an End. PTP1B-WT mouse (first column, second row). This was inserted during the preparation of the figure in error and has now been corrected. This matter was investigated by the ESC Journals Family Ethics Committee, who recommended this resolution. This change does not affect the overall scientific message of the paper. The ESC Journal Ethics Committee assigned for the Journal Cardiovascular Research has chosen to neglect the 2$nd$ occurrence of image duplication in this article, as described in Comment #2 and again below. ![file] ,