Activation of MAP kinase in vivo follows balloon overstretch injury of porcine coronary and carotid arteries.
Activation of MAP kinase in vivo follows balloon overstretch injury of porcine coronary and carotid arteries.
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DOI：
10.1161/01.res.81.6.904
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发表时间：
1997-12
影响因子：
20.1
通讯作者：
J. Pyles;K. March;M. Franklin;Kamal Mehdi;R. Wilensky;L. Adam
中科院分区：
文献类型：
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作者：
J. Pyles;K. March;M. Franklin;Kamal Mehdi;R. Wilensky;L. Adam
血管再狭窄涉及过度拉伸损伤后动脉壁的收缩、增殖和重塑。丝裂原活化蛋白激酶（MAPKs）参与血管平滑肌（VSM）的收缩和增殖，对猪颈动脉肌条的研究表明，机械拉伸会激活细胞外信号调节激酶（ERK）家族的MAPKs。因此，我们分析了机械过度拉伸损伤对猪冠状动脉和颈动脉ERK-MAPK（以下简称MAPK）活性的急性影响。在猪冠状动脉或颈动脉中，球囊血管成形术导管在5分钟内以1.2:1的球囊-动脉比例充气至6atm三次。血管成形术后快速冻结动脉，测量MAPK活性。与未使用仪器的右冠状动脉（RCAs）或颈动脉相比，左前降支动脉（LAD, n = 5）、左旋支动脉（LCx, n = 5）和颈动脉（n = 5）的血管成形术使MAPK活性增加。颈动脉球囊成形术导致MAPK活性增加，是对照动脉活性的7.7倍，与体内拉伸颈动脉肌条的活性相当。冠脉激酶活性的增加在不同动物血管成形术中是不同的。与对照动脉相比，左冠状动脉的MAPK活性增加了4.5- 31.7倍（平均+/- SEM， 10.7 +/- 5.3），左冠状动脉的MAPK活性增加了1.8- 31.3倍（平均+/- SEM， 9.7 +/- 5.7）。三种不同类型冠状动脉（RCA， LAD和LCx）的MAPK活性水平没有明显的内在差异。MAPK在血管成形术中迅速激活，这表明该激酶可能在启动猪冠状动脉和颈动脉损伤反应中起早期作用。MAPKs可能是治疗或预防再狭窄的关键酶。
Vascular restenosis involves contraction, proliferation, and remodeling of the arterial wall in response to overstretch injury. Mitogen-activated protein kinases (MAPKs) are implicated in both contraction and proliferation of vascular smooth muscle (VSM), and studies of porcine carotid arterial muscle strips have shown that mechanical stretch leads to the activation of the extracellular signal-regulated kinase (ERK) family of MAPKs in vivo. We, therefore, analyzed the acute effect of mechanical overstretch injury on ERK-MAPK (herein referred to simply as MAPK) activity in porcine coronary and carotid arteries in vivo. Balloon angioplasty catheters were inflated to 6 atm three times over 5 minutes at a balloon-artery ratio of 1.2:1 in either porcine coronary or carotid arteries. The arteries were snap-frozen after angioplasty, and MAPK activity was measured. Angioplasty of the left anterior descending (LAD, n = 5), left circumflex (LCx, n = 5), and carotid (n = 5) arteries effected an increase in MAPK activity compared with the activity in uninstrumented right coronary arteries (RCAs) or carotid arteries from the same animals used for controls. Balloon angioplasty of carotid arteries led to an increase in MAPK activity that was 7.7-fold over the activity in control arteries and comparable to the activity in stretched carotid arterial muscle strips in vivo. The increase in coronary artery kinase activity on angioplasty was variable from animal to animal. The increase in MAPK activity over that in control arteries ranged from 4.5- to 31.7-fold (mean +/- SEM, 10.7 +/- 5.3) in the LAD and 1.8- to 31.3-fold (mean +/- SEM, 9.7 +/- 5.7) in the LCx. There were no apparent inherent differences in the levels of MAPK activity in the three different types of coronary arteries (RCA, LAD, and LCx) without instrumentation. MAPK activation occurs rapidly during angioplasty, suggesting that this kinase may play an early role in initiating the injury response in both porcine coronary and carotid arteries. MAPKs may be key enzymes targeted to treat or prevent restenosis.