CD45 Expression in Mitral Valve Endothelial Cells After Myocardial Infarction.
CD45 Expression in Mitral Valve Endothelial Cells After Myocardial Infarction.
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DOI：
10.1161/circresaha.116.309598
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发表时间：
2016-11-11
影响因子：
20.1
通讯作者：
Levine RA
中科院分区：
文献类型：
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作者：
Bischoff J;Casanovas G;Wylie-Sears J;Kim DH;Bartko PE;Guerrero JL;Dal-Bianco JP;Beaudoin J;Garcia ML;Sullivan SM;Seybolt MM;Morris BA;Keegan J;Irvin WS;Aikawa E;Levine RA
缺血性二尖瓣反流(IMR)是心肌梗死(MI)后的一种并发症，可诱导适应性二尖瓣反应，这种反应最初可能是有益的，但最终会导致叶纤维化和二尖瓣功能障碍。我们试图研究MV内皮反应及其对IMR的潜在贡献。对MI后绵羊MVS中的内皮细胞、间质细胞和造血细胞进行了定量。对MI后发现的MV内皮细胞CD45进行体外分析。下壁心肌梗死(IMI)后6个月采集的绵羊MVS显示CD45蛋白酪氨酸磷酸酶与血管内皮细胞标志物von Willebrand因子共定位。流式细胞仪检测显示，与假手术组和正常组相比，缺血再灌注组中CD45阳性的内皮细胞(VE-钙粘附素+/CD45+/α-平滑肌肌动蛋白+和VE-钙粘附素+/CD45+/α-平滑肌肌动蛋白-细胞)和可能的纤维细胞(VE-钙粘附素-/CD45+/αSMA+)明显增加。CD45+细胞与MV纤维化程度及MR严重程度相关。VE-钙粘蛋白+/CD45+/CD45SMA+细胞提示α可能与内皮-间充质转化有关。经转化生长因子β1诱导的血管内皮细胞表达CD45和纤维化标志物胶原1、3及转化生长因子β1-3，而未见转化生长因子β1诱导的血管内皮细胞表达CD45和纤维化标志物胶原1、3及转化生长因子CD1-3。CD45蛋白酪氨酸磷酸酶抑制剂可阻断EndMT和纤维化标志物的诱导，并抑制EndMT相关的血管内皮细胞迁移。心肌梗死后和体外培养的血管内皮细胞均表达β，CD45磷酸酶抑制剂可阻断血管内皮细胞表达EndMT的标志。这些结果指出了EndMT对CD45磷酸酶活性的一种新的功能需求。CD45+内皮细胞在心肌梗死后MV适应和纤维化中的作用值得研究。
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. Endothelial, interstitial and hematopoietic cells in MVs from post-MI sheep were quantified. MV endothelial CD45, found post-MI, was analyzed in vitro. 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. 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.