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This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/H2388    most recent 01313.2005v2 01313.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Fukunaga, R. Articles by Kanaide, H. Search for Related Content PubMed PubMed Citation Articles by Fukunaga, R. Articles by Kanaide, H.

Upregulation of proteinase-activated receptors and hypercontractile responses precede development of arterial lesions after balloon injury

¹Division of Molecular Cardiology, Research Institute of Angiocardiology; ²Department of Surgery and Science, Graduate School of Medical Sciences; and ³Kyushu University Center of Excellence Program on Lifestyle-Related Diseases, Kyushu University, Fukuoka, Japan

Submitted 13 December 2005 ; accepted in final form 5 July 2006

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 Ca²⁺ sensitivity of the contractile apparatus as evaluated in the permeabilized preparations. PAR-1-activating peptide (100 µmol/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.

thrombin; protease; vascular tone; vascular injury