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Podoplanin neutralization improves cardiac remodeling and function after acute myocardial infarction.

Publication ,  Journal Article
Cimini, M; Garikipati, VNS; de Lucia, C; Cheng, Z; Wang, C; Truongcao, MM; Lucchese, AM; Roy, R; Benedict, C; Goukassian, DA; Koch, WJ; Kishore, R
Published in: JCI Insight
July 9, 2019

Podoplanin, a small mucine-type transmembrane glycoprotein, has been recently shown to be expressed by lymphangiogenic, fibrogenic and mesenchymal progenitor cells in the acutely and chronically infarcted myocardium. Podoplanin binds to CLEC-2, a C-type lectin-like receptor 2 highly expressed by CD11bhigh cells following inflammatory stimuli. Why podoplanin expression appears only after organ injury is currently unknown. Here, we characterize the role of podoplanin in different stages of myocardial repair after infarction and propose a podoplanin-mediated mechanism in the resolution of post-MI inflammatory response and cardiac repair. Neutralization of podoplanin led to significant improvements in the left ventricular functions and scar composition in animals treated with podoplanin neutralizing antibody. The inhibition of the interaction between podoplanin and CLEC-2 expressing immune cells in the heart enhances the cardiac performance, regeneration and angiogenesis post MI. Our data indicates that modulating the interaction between podoplanin positive cells with the immune cells after myocardial infarction positively affects immune cell recruitment and may represent a novel therapeutic target to augment post-MI cardiac repair, regeneration and function.

Duke Scholars

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Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

July 9, 2019

Volume

5

Issue

15

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function, Left
  • Vasoconstrictor Agents
  • Regeneration
  • Myocytes, Cardiac
  • Myocardial Ischemia
  • Myocardial Infarction
  • Monocytes
  • Mice
  • Membrane Glycoproteins
 

Citation

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Cimini, M., Garikipati, V. N. S., de Lucia, C., Cheng, Z., Wang, C., Truongcao, M. M., … Kishore, R. (2019). Podoplanin neutralization improves cardiac remodeling and function after acute myocardial infarction. JCI Insight, 5(15). https://doi.org/10.1172/jci.insight.126967
Cimini, Maria, Venkata Naga Srikanth Garikipati, Claudio de Lucia, Zhongjian Cheng, Chunlin Wang, May M. Truongcao, Anna Maria Lucchese, et al. “Podoplanin neutralization improves cardiac remodeling and function after acute myocardial infarction.JCI Insight 5, no. 15 (July 9, 2019). https://doi.org/10.1172/jci.insight.126967.
Cimini M, Garikipati VNS, de Lucia C, Cheng Z, Wang C, Truongcao MM, et al. Podoplanin neutralization improves cardiac remodeling and function after acute myocardial infarction. JCI Insight. 2019 Jul 9;5(15).
Cimini, Maria, et al. “Podoplanin neutralization improves cardiac remodeling and function after acute myocardial infarction.JCI Insight, vol. 5, no. 15, July 2019. Pubmed, doi:10.1172/jci.insight.126967.
Cimini M, Garikipati VNS, de Lucia C, Cheng Z, Wang C, Truongcao MM, Lucchese AM, Roy R, Benedict C, Goukassian DA, Koch WJ, Kishore R. Podoplanin neutralization improves cardiac remodeling and function after acute myocardial infarction. JCI Insight. 2019 Jul 9;5(15).

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

July 9, 2019

Volume

5

Issue

15

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function, Left
  • Vasoconstrictor Agents
  • Regeneration
  • Myocytes, Cardiac
  • Myocardial Ischemia
  • Myocardial Infarction
  • Monocytes
  • Mice
  • Membrane Glycoproteins