Mechanical stretch induces phosphorylation of p38-MAPK and apoptosis in human saphenous vein
Mechanical stretch induces phosphorylation of p38-MAPK and apoptosis in human saphenous vein
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DOI：
10.1161/01.atv.0000116690.17017.8b
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发表时间：
2004-03-01
影响因子：
8.7
通讯作者：
Holt, CM
中科院分区：
文献类型：
--
作者：
Cornelissen, J;Armstrong, J;Holt, CM
目的：大隐静脉移植失败仍然是冠状动脉搭桥手术的主要限制.本研究的目的是确定是否压力扩张的人隐静脉诱导p38-MAPK的激活，并确定其在apoptosis.Methods和Results中的作用-磷酸化p38被检测到在基础水平的人隐静脉收获后立即获得。扩张的大隐静脉在切取后3 h和6 h的磷酸化p38水平均显著高于对照静脉（P <0.01）。扩张和非扩张静脉中的细胞凋亡在24小时时显著高于对照静脉，扩张静脉在所有研究时间点均显示出比非扩张隐静脉更高的细胞凋亡（P < 0.001）。免疫组化显示磷酸化p38和凋亡共定位。抑制p38活性可使培养的血管平滑肌细胞的凋亡指数降低72.1% +/- 1.2%，使培养的扩张的大隐静脉节段的凋亡指数降低72.7% +/-0.9%。抑制隐静脉平滑肌细胞和完整静脉中p38激酶活性可减少细胞凋亡。这些发现有助于我们理解隐静脉移植失败的机制。
Objective - Failure of saphenous vein grafts remains a major limitation of coronary bypass surgery. The aims of the present study were to determine whether pressure distension of human saphenous vein induces the activation of p38-MAPK and to determine its role in apoptosis.Methods and Results - Phosphorylated p38 was detected at basal levels in human saphenous vein obtained immediately after harvesting. Distended saphenous vein showed significantly higher levels of phosphorylated p38 compared with control vein (P < 0.01) and nondistended saphenous vein maintained for 3 and 6 hours after harvesting (both P < 0.01). Apoptosis in distended and nondistended vein was significantly higher at 24 hours compared with control vein, with distended vein showing increased apoptosis compared with nondistended saphenous vein at all time points investigated (P < 0.001). Immunolocalization showed co-localization of phosphorylated p38 and apoptosis. Inhibition of p38 activity reduced the apoptotic index of cultured vascular smooth muscle cells by 72.1% +/- 1.2% and cultured distended saphenous vein segments by 72.7% +/- 0.9%.Conclusions - Pressure distension of intact human saphenous vein induces activation of p38, and this is associated with apoptosis. Inhibition of p38 kinase activity in saphenous vein smooth muscle cells and intact vein reduces apoptosis. These findings contribute to our understanding of the mechanisms of saphenous vein graft failure.