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Podoplanin neutralization improves cardiac remodeling and function after myocardial infarction
Maria Cimini, … , Walter J. Koch, Raj Kishore
Maria Cimini, … , Walter J. Koch, Raj Kishore
Published July 9, 2019
Citation Information: JCI Insight. 2019;4(15):e126967. https://doi.org/10.1172/jci.insight.126967.
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Research Article Cardiology Cell biology

Podoplanin neutralization improves cardiac remodeling and function after myocardial infarction

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Abstract

Podoplanin (PDPN), a small mucin-type transmembrane glycoprotein, has been recently shown to be expressed by lymphangiogenic, fibrogenic, and mesenchymal progenitor cells in the acutely and chronically infarcted myocardium. PDPN binds to a C-type lectin–like receptor 2 highly expressed by CD11bhi cells following inflammatory stimuli. Why PDPN expression appears only after organ injury is currently unknown. Here, we characterize the role of PDPN in different stages of myocardial repair after infarction and propose a PDPN-mediated mechanism in the resolution of post–myocardial infarction (MI) inflammatory response and cardiac repair. Neutralization of PDPN led to significant improvements in the left ventricular (LV) functions and scar composition in animals treated with PDPN-neutralizing antibody. The inhibition of the interaction between PDPN and C-type lectin–like receptor 2 expressing immune cells in the heart enhances the cardiac performance, regeneration, and angiogenesis after MI. Our data indicate that modulating the interaction between PDPN-positive cells with the immune cells after MI positively affects immune cell recruitment and may represent a novel therapeutic target to augment post-MI cardiac repair, regeneration, and function.

Authors

Maria Cimini, Venkata Naga Srikanth Garikipati, Claudio de Lucia, Zhongjian Cheng, Chunlin Wang, May M. Truongcao, Anna Maria Lucchese, Rajika Roy, Cindy Benedict, David A. Goukassian, Walter J. Koch, Raj Kishore

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Figure 3

PDPN neutralization improves LV function after MI.

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PDPN neutralization improves LV function after MI.
Scatter plots represe...
Scatter plots representing EF percentage (A), percentage of FS (B), LV end-diastolic diameter (C), and LV end-systole diameter (D) as measured by echocardiography at baseline and at 7 and 30 days after MI in mice treated with PDPN-neutralizing Ab (n = 12/group), isotype-matched IgG (n = 10/group), or saline (n = 12/group). Data are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, control versus treated at 30 days after MI. #P < 0.05, ##P < 0.01, IgG control versus treated at 30 days after MI. $P < 0.05 control versus IgG control at 30 days after MI. Two-way ANOVA and Bonferroni’s post hoc test were performed among all groups.

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