TY - JOUR
T1 - Podoplanin neutralization improves cardiac remodeling and function after myocardial infarction
AU - Cimini, Maria
AU - Srikanth Garikipati, Venkata Naga
AU - de Lucia, Claudio
AU - Cheng, Zhongjian
AU - Wang, Chunlin
AU - Truongcao, May M.
AU - Lucchese, Anna Maria
AU - Roy, Rajika
AU - Benedict, Cindy
AU - Goukassian, David A.
AU - Koch, Walter J.
AU - Kishore, Raj
N1 - Publisher Copyright:
: © 2019 American Society for Clinical Investigation
PY - 2019/8/8
Y1 - 2019/8/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85070795988&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.126967
DO - 10.1172/jci.insight.126967
M3 - Article
C2 - 31287805
AN - SCOPUS:85070795988
SN - 2379-3708
VL - 4
JO - JCI insight
JF - JCI insight
IS - 15
M1 - e126967
ER -