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首页> 外文期刊>American Journal of Physiology >Upregulation of proteinase-activated receptors and hypercontractile responses precede development of arterial lesions after balloon injury.
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Upregulation of proteinase-activated receptors and hypercontractile responses precede development of arterial lesions after balloon injury.

机译：球囊损伤后，在动脉病变发展之前，蛋白酶激活受体的上调和过度收缩反应。

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摘要

Thrombin and other proteinases exert vascular effects by activating the proteinase-activated receptors (PARs). The expression of PARs has been shown to be upregulated after balloon injury and in human arteriosclerosis. However, the relationship between the receptor upregulation and the alteration of vasomotor function remains to be elucidated. We herein demonstrated that the contractile responses to the PAR-1 and PAR-2 agonist were markedly enhanced in the rabbit femoral arteries after balloon injury. Neointimal thickening was established 4 wk after the injury. No histological change was observed in the sham operation, where the saphenous artery was ligated without any balloon injury. The contractile response to K(+) depolarization was significantly attenuated 1 wk after the injury and then partly recovered after 4 wk. Thrombin, PAR-1-activating peptide, trypsin, and PAR-2-activating peptide induced no significant contraction in the control. All these stimulants induced enhanced responses 1 wk after balloon injury. Such enhanced responses were seen 4 wk after the injury, except for thrombin. There was no change in the Ca(2+) sensitivity of the contractile apparatus as evaluated in the permeabilized preparations. PAR-1-activating peptide (100 mumol/l), but no other stimulants, induced an enhanced contraction in the sham operation. The expression of PAR-1 and PAR-2 slightly increased after the sham operation, whereas it markedly and significantly increased after balloon injury. Our observations suggest that balloon injury induced the receptor upregulation, thereby enhancing the contractile response before the establishment of vascular lesions. The local inflammation associated with the sham operation may also contribute to the receptor upregulation.
机译：凝血酶和其他蛋白酶通过激活蛋白酶激活的受体（PAR）发挥血管作用。球囊损伤后和人类动脉硬化中，PARs的表达已被上调。但是，受体上调与血管舒缩功能改变之间的关系仍有待阐明。我们在本文中证明，气球损伤后兔股动脉中对PAR-1和PAR-2激动剂的收缩反应明显增强。损伤后4周建立新内膜增厚。在假手术中未观察到组织学变化，假手术中结扎了大隐动脉，没有任何球囊损伤。受伤后1周，对K（+）去极化的收缩反应明显减弱，然后在4周后部分恢复。凝血酶，PAR-1激活肽，胰蛋白酶和PAR-2激活肽在对照组中未引起明显收缩。所有这些刺激物在球囊损伤后1周引起增强的反应。除凝血酶外，损伤后4周观察到这种增强的反应。如在透化制剂中评估的，收缩装置的Ca（2+）敏感性没有变化。 PAR-1激活肽（100摩尔/升），但没有其他刺激物，在假手术中诱导增强的收缩。假手术后，PAR-1和PAR-2的表达略有增加，而在球囊损伤后，PAR-1和PAR-2的表达显着增加。我们的观察结果表明，球囊损伤可引起受体上调，从而在建立血管病变之前增强收缩反应。与假手术相关的局部炎症也可能导致受体上调。

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