CD45 Expression in Mitral Valve Endothelial Cells After Myocardial Infarction
Rationale: Ischemic mitral regurgitation (IMR), 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 IMR.
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 (IMI), showed CD45, a protein tyrosine phosphatase, co-localized with von Willebrand factor, an endothelial marker. Flow cytometry of MV cells revealed significant increases in CD45-positive endothelial cells (VE-Cadherin+/CD45+/α-smooth muscle actin (SMA)+ and VE-cadherin+/CD45+/αSMA- cells) and possible fibrocytes (VE-Cadherin-/CD45+/ αSMA+) in IMI compared to sham-operated and normal sheep. CD45+ cells correlated with MV fibrosis and MR severity. VE-cadherin+/CD45+/αSMA+ cells suggested CD45 may be linked to endothelial-to-mesenchymal transition (EndMT). MV endothelial cells treated with TGFβ1 to induce EndMT expressed CD45 and fibrosis markers collagen 1 and 3 and TGFβ1-3, not observed in TGFβ1-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 TGFβ1. 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.
- valve endothelial cells
- endothelial to mesenchymal transition
- endothelial cell differentiation
- endothelial cell
- mitral regurgitation
- mitral valve
- myocardial infarction
- Received July 19, 2016.
- Revision received September 14, 2016.
- Accepted September 15, 2016.