Abstract
Proteinase-activated receptors (PARs) play critical roles in vascular physiology and pathophysiology. Under physiological conditions, PARs are mainly expressed in endothelial cells, while mostly inducing endothelium-dependent relaxation. However, the expression of PARs in smooth muscle of normal artery is generally limited. We found that balloon injury in rabbit femoral artery upregulated the expression of PAR1 and PAR2 in smooth muscle, and enhanced the contractile responses to thrombin and trypsin within 1 week. Thereafter, the proliferative vascular lesion became obvious. A cyclooxygenase inhibitor partly prevented the upregulation of PAR1 but not PAR2, and attenuated the contractile response to thrombin. We also found that the PAR1 expression was up-regulated and the contractile response to thrombin were markedly augmented in rabbit basilar artery of subarachnoid hemorrhage model, which received the intracisternal injections of autologous blood. Heparinization of autologous blood or treatment with PAR1 antagonist partly prevented the PAR1 upregulation and the enhancement of the contractile response. The up-regulation of PARs in smooth muscle is thus considered to be a key step for PARs to participate in the pathogenesis of vascular lesions and augmentation of the vascular contractility. Thrombin and PAR1 play a key role in upregulating PAR1 in subarachnoid hemorrhage, while cyclooxygenase is involved in the PAR1 upregulation seen after balloon injury. Elucidating the molecular mechanism regulating PARs expression is thus the next important step in PARs research. [J Physiol Sci. 2007;57 Suppl:S60]
