Role of protease-activated receptor 2 in metabolic syndrome

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590315
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Mukogawa Women's University
• Principal Investigator: KAGOTA Satomi 武庫川女子大学, 薬学部, 准教授 (00291807)
• Co-Investigator(Renkei-kenkyūsha): MARUYAMA Kana 武庫川女子大学, 薬学部, 助手 (20611396)
• Project Period (FY): 2011 – 2013
• Keywords: 血管拡張機能 / メタボリックシンドローム / PAR-2 / 一酸化窒素

Research Abstract

Metabolic syndrome (MetS) is characterized by accumulation of atherosclerotic risk. Increased visceral adiposity is attributed to the development of cardiovascular complications in the syndrome via overproduction of inflammatory factors released from adipocytes. However, the role of protease-activated receptor 2 (PAR2) in vascular responsiveness in MetS is not fully understood. Therefore, we studied changes in PAR2-mediated vasodilation using an animal model of MetS.
Our study demonstrates that PAR2-mediated vasodilation is preserved even though nitric oxide (NO)-mediated vasodilation by other agonists is impaired in arteries of MetS rats. Enhancement of endothelial NO synthase may play important role in the preservation of PAR2-mediated vasodilation. Furthermore, we propose that perivascular adipose tissue wrapped around the blood vessel enhances NO-mediated vasodilation under pathophysiological conditions to compensate for impaired vasodilation in MetS.

Research Products

• [Journal Article] Chronic oxidative-nitrosative stress impairs coronary vasodilation in metabolic syndrome model rats (2013)
  • Author(s): Kagota S., Maruyama K., Tada Y., Fukushima K., Umetani K., Wakuda H., Shinozuka K.
  • Journal Title: Microvascular Research Volume: 88 Pages: 70-78
• [Journal Article] Abnormal amount of intracellular calcium regulatory proteins in SHRSP.Z-Lepr^fa/IzmDmcr rats with metabolic syndrome and cardiac dysfunction (2013)
  • Author(s): Kagota S., Maruyama K., Tada Y., Wakuda H., Nakamura K., Kunitomo M., Shinozuka K.
  • Journal Title: Canadian Journal of Physiology and Pharmacology Volume: 91 Pages: 124-133
• [Journal Article] Effects of telmisartan on arterial vasodilation via protease-activated receptor-2 activation in SHRSP.Z-Lepr^fa/IzmDmcr rats with metabolic syndrome (2013)
  • Author(s): Kagota S., Maruyama K., Wakuda H., McGuire J.J., Yoshikawa N., Nakamura K., Shinozuka K.
  • Journal Title: Proceedings of the 10th International Congress on Coronary Artery Disease(Eds; Lewis BS., Borer JS., Flugelman MY., Halon DA.) Pages: 139-142
• [Journal Article] Telmisartan prevents impairment of vasodilation via protease-activated receptor 2 in SHRSP.Z-Lepr^fa/IzmDmcr rats with metabolic syndrome
  • Author(s): Kagota S., Maruyama K., Wakuda H., McGuire JJ., Yoshikawa N., Nakamura K., Shinozuka K.
  • Journal Title: Vascular Pharmacology Volume: (submitted)
• [Presentation] The mechanisms of preservation of vasorelaxation induced by protease-activated receptor-2 activation in aorta of metabolic syndrome rats (2014)
  • Author(s): Maruyama K., Kagota S., Wakuda H., McGuire JJ., Yoshikawa N., Nakamura K., Kunitomo M., Shinozuka K.
  • Organizer: ATVB 2014
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2014-05-03
• [Presentation] Influence of perivascular adipose tissue on vasodilation in metabolic syndrome (2014)
  • Author(s): Kagota S., Maruyama K., Iwata S., Wakuda H., Yoshikawa N., Nakamura K., Shinozuka K.
  • Organizer: ATVB 2014
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2014-05-03
• [Presentation] メタボリックシンドロームモデルSHRSP.Z-Lepr^fa/IzmDmcrラット大動脈に生じるプロテアーゼ活性化型受容体-2を介する拡張機能の保持機構 (2014)
  • Author(s): 丸山加菜, 籠田智美, 和久田浩一, John J McGuire, 吉川紀子, 中村一基, 国友勝, 篠塚和正
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
  • Year and Date: 2014-03-29
• [Presentation] メタボリックシンドロームにおける血管拡張機能と血管周囲脂肪 (2014)
  • Author(s): 籠田智美, 丸山加菜, 篠塚和正
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
  • Year and Date: 2014-03-21
• [Presentation] Effects of telmisartan on arterial vasodilation via protease-activated receptor-2 activation in SHRSP.Z-Lepr^fa/IzmDmcr rats with metabolic syndrome (2013)
  • Author(s): Kagota S., Maruyama K., Wakuda H., McGuire JJ., Yoshikawa N., Nakamura K., Shinozuka K.
  • Organizer: International Congress on Coronary Artery Disease
  • Place of Presentation: Florence, Italy
  • Year and Date: 2013-10-15
• [Presentation] メタボリックシンドロームモデルSHRSP.Z-Lepr^fa/IzmDmcrラットの左室拡張機能障害の機序 (2013)
  • Author(s): 籠田智美, 丸山加菜, 多田有加里, 和久田浩一, 吉川紀子, 中村一基
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2013-03-22
• [Presentation] 加齢に伴うメタボリックシンドロームラットのプロテアーゼ活性化型受容体-2依存性血管拡張機能の変化 (2013)
  • Author(s): 丸山加菜, 籠田智美, 和久田浩一, John J. McGuire, 吉川紀子, 中村一基, 篠塚和正
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2013-03-21
• [Presentation] Chronic administration of tempol protects impaired coronary vasodilation in metabolic syndrome model rats, SHRSP.Z-Lepr^fa/IzmDmcr rats (2012)
  • Author(s): Kagota S., Maruyama K., Fukushima K., Umetani K., Tada Y., Wakuda H., Kunitomo M., Nakamura K., Shinozuka K.
  • Organizer: 24th ISH2012
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2012-10-03
• [Presentation] Preserved vasodilation via activation of protease-activated receptor-2 in SHRSP.Z-Lepr^fa/IzmDmcr rats with metabolic syndrome (2012)
  • Author(s): Maruyama K., Kagota S., Wakuda H., McGuire JJ., Nakamura K., Kunitomo M., Shinozuka K.
  • Organizer: 24th ISH2012
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2012-10-01
• [Presentation] Cardiac dysfunction in SHRSP.Z-Lepr^fa/IzmDmcr rats with metabolic syndrome (2012)
  • Author(s): Kagota S., Tada Y., Maruyama K., Wakuda H., Nakamura K., Kunitomo M., Shinozuka K.
  • Organizer: 3rd International Congress on Abdominal Obesity
  • Place of Presentation: Quebec, Canada
  • Year and Date: 2012-07-11
• [Presentation] メタボリックシンドロームモデルSHRSP.Z-Lepr^fa/IzmDmcrラットの冠動脈拡張機能障害に対するTempolの予防効果 (2012)
  • Author(s): 籠田智美, 多田有加里, 福島和人, 梅谷啓二, 丸山加菜, 和久田浩一, 国友勝, 中村一基, 篠塚和正
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-14
• [Presentation] メタボリックシンドロームモデルSHRSP.Z-Lepr^fa/IzmDmcrラットのプロティナーゼ活性化型受容体-2を介した血管弛緩反応性 (2012)
  • Author(s): 丸山加菜, 籠田智美, 和久田浩一, John J. McGuire, 中村一基, 国友勝, 篠塚和正
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-14