CD45 Expression in Mitral Valve Endothelial Cells After Myocardial Infarction. Issue 11 (11th November 2016)

• Record Type: Journal Article
• Authors: Bischoff, Joyce; Casanovas, Guillem; Wylie-Sears, Jill; Kim, Dae-Hee; Bartko, Philipp E.; Guerrero, J. Luis; Dal-Bianco, Jacob P.; Beaudoin, Jonathan; Garcia, Michael L.; Sullivan, Suzanne M.; Seybolt, Margo M.; Morris, Brittan A.; Keegan, Joshua; Irvin, Whitney S.; Aikawa, Elena; Levine, Robert A.
• Is Part Of: Circulation research. Volume 119:Issue 11(2016)
• Publication Date: 2016-11-11
• Subjects: endothelial cell -- endothelial cell differentiation -- flow cytometry -- mitral valve -- myocardial infarction; Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.116.309598
• Languages: English
• ISSNs: 0009-7330

Abstract

Abstract : Rationale : : Ischemic mitral regurgitation, a complication after myocardial infarction (MI), induces adaptive mitral valve (MV) responses that may be initially beneficial but eventually lead to leaflet fibrosis and MV dysfunction. We sought to examine the MV endothelial response and its potential contribution to ischemic mitral regurgitation. Objective : : Endothelial, interstitial, and hematopoietic cells in MVs from post-MI sheep were quantified. MV endothelial CD45, found post MI, was analyzed in vitro. Methods and Results : : Ovine MVs, harvested 6 months after inferior MI, showed CD45, a protein tyrosine phosphatase, colocalized with von Willebrand factor, an endothelial marker. Flow cytometry of MV cells revealed significant increases in CD45 + endothelial cells (VE-cadherin + /CD45 + /α-smooth muscle actin [SMA] + and VE-cadherin + /CD45 + /αSMA− cells) and possible fibrocytes (VE-cadherin − /CD45 + /αSMA + ) in inferior MI compared with sham-operated and normal sheep. CD45 + cells correlated with MV fibrosis and mitral regurgitation severity. VE-cadherin + /CD45 + /αSMA + cells suggested that CD45 may be linked to endothelial-to-mesenchymal transition (EndMT). MV endothelial cells treated with transforming growth factor-β1 to induce EndMT expressed CD45 and fibrosis markers collagen 1 and 3 and transforming growth factor-β1 to 3, not observed in transforming growth factor-β1–treated arterial endothelial cells. A CD45 protein tyrosine phosphatase inhibitor blocked induction of EndMT and fibrosis markers and inhibited EndMT-associated migration of MV endothelial cells. Conclusions : : MV endothelial cells express CD45, both in vivo post MI and in vitro in response to transforming growth factor-β1. A CD45 phosphatase inhibitor blocked hallmarks of EndMT in MV endothelial cells. These results point to a novel, functional requirement for CD45 phosphatase activity in EndMT. The contribution of CD45 + endothelial cells to MV adaptation and fibrosis post MI warrants investigation. Abstract : Supplemental Digital Content is available in the text.