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

Ryota Fukunaga, Katsuya Hirano, Mayumi Hirano, Naohisa Niiro, Junji Nishimura, Yoshihiko Maehara, Hideo Kanaide

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number5
DOIs
Publication statusPublished - Nov 24 2006

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Proteinase-Activated Receptors
Up-Regulation
PAR-1 Receptor
Wounds and Injuries
PAR-2 Receptor
Thrombin
Peptides
Blood Vessels
Arteriosclerosis
Femoral Artery
Trypsin
Peptide Hydrolases
Arteries
Rabbits
Inflammation

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Upregulation of proteinase-activated receptors and hypercontractile responses precede development of arterial lesions after balloon injury. / Fukunaga, Ryota; Hirano, Katsuya; Hirano, Mayumi; Niiro, Naohisa; Nishimura, Junji; Maehara, Yoshihiko; Kanaide, Hideo.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 291, No. 5, 24.11.2006.

Research output: Contribution to journalArticle

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