EFFECTS OF EXAGGERATED BLOOD PRESSURE VARIABILITY ON CARDIAC REMODELING AND PERIVASCULAR INFLAMMATION

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15590780
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: KURUME UNIVERSITY
• Principal Investigator: KAI Hisashi Kurume University, School of Medicine, Associate Professor, 医学部, 助教授 (60281531)
• Co-Investigator(Kenkyū-buntansha): IMAIZUMI Tsutomu Kurume University, School Of Medicine, Professor, 医学部, 教授 (60148947) ; KUWAHARA Fumitaka Kurume University, School Of Medicine, Assistant Professor, 医学部, 助手 (90279167) ; NIIYAMA Hiroshi Kurume University, School Of Medicine, Assistant Professor, 医学部, 助手 (30309778)
• Project Period (FY): 2003 – 2004
• Keywords: blood pressure variability / myocardial fibrosis / hypertension / hypertrophy / macrophages / アンジオテンシンII / 拡張障害

Research Abstract

(1)To clarify the mechanism whereby wide blood pressure variability induces exaggerated hypertensive organ damages, we created new animal model of hypertension with large blood pressure variability by performing bilateral sino-aortic denervation(SAD) in spontaneously hypertensive rats(SHRs).
(2)In SHR+SAD, mean blood pressure elevated to the similar level to that in SHR+sham operation. However, parameters of blood pressure variability, such as standard deviation of mean blood pressure and coefficent of variation of mean blood pressure, were significantly larger in SHR+SAD than in SHR+sham operation.
(3)SHR+SAD had enhanced left ventricular hypertrophy and severer myocardial fibrosis, compared with SHR+sham operetion.
(4)SAD remarkably upregulated myocardial MCP-1 expression and enhanced perivascular macrophage infiltration in the hearts of SHR.

Research Products

• [Journal Article] Pressure-independent effects of angiotensin II on hypertensive myocardial fibrosis (2004)
  • Author(s): Tokuda K, Kai H(他8名2番目)
  • Journal Title: Hypertension 43(2) Pages: 499-503
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Pressure-independent effects of angiotensin II on hypertensive myocardial fibrosis. (2004)
  • Author(s): Tokuda K, Kai H, Kuwahara F, Yasukawa H, Tahara N, Kudo H, Takemiya K, Koga M, Yamamoto T, Imaizumi T.
  • Journal Title: Hypertension 43(2 pt2) Pages: 499-503
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hypertensive myocardial fibrosis and diastolic dysfunction-Another model of inflammation- (2004)
  • Author(s): Kuwahara F, Kai H, Tokuda K, Takeya M, Takeshita A, Egashira K, Imaizumi T.
  • Journal Title: Hypertension 43(4) Pages: 739-745
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Roles of endogenous monocyte chemoattractant protein-1 in ischemia-induced neovascularization.. (2004)
  • Author(s): Niiyama H, Kai H, Yamamoto T, Shimada T, Sasaki K, Murohara T, Egashira K, Imaizumi T.
  • Journal Title: J Am Coll Cardiol 44(3) Pages: 661-666
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Repeated gene transfers of naked prostacyclin synthase plasmid into skeletal muscles attenuate monocrotaline-induced pulmonary hypertension and prolong survival in rats. (2004)
  • Author(s): Tahara N, Kai H, Niiyama H, Mori T, Sugi Y, Takayama N, Yasukawa H, Numaguchi Y, Matsui H, Okamura K, Imaizumi T.
  • Journal Title: Human Gene Ther 15(12) Pages: 1270-1278
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] an IL-6 family cytokine, upregulates matrix metalloproteinase-9 through the MEK-ERK pathway in cultured smooth muscle cells. (2003)
  • Author(s): Nagata T, Kai H, Shibata R, Koga M, Yoshimura A, Imaizumi T, Oncostatin M
  • Journal Title: Arterioscl Thromb Vasc Biol 23 Pages: 588-593
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of STAT3 prevents neointime formation by inhibiting proliferation and promoting apoptosis of neointimal smooth muscle cells. (2003)
  • Author(s): Shibata R, Kai H, Seki Y, Kato S, Wada Y, Hanakawa Y, Hashimoto K, Yoshimura A, Imaizumi T.
  • Journal Title: Human Gene Ther 14(7) Pages: 601-610
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Rho-kinase inhibition reduces neointima formation after vascular injury by enhancing Bax expression and apoptosis (2003)
  • Author(s): Shibata R, Kai H, Seki Y, Kusaba K, Takemiya K, Koga M, Jalalidin A, Tokuda K, Tahara N, Niiyama H, Nagata T, Kuwahara F, Imaizumi T.
  • Journal Title: J Cardiovasc Pharmacol 42(suppl) Pages: S43-S47
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Sub-depressor dose of angiotensin type-1 receptor blocker inhibits TGF-β-mediated perivascular fibrosis in hypertensive rat hearts. (2003)
  • Author(s): Tokuda K, Kai H, Kuwahara F, Imaizumi T
  • Journal Title: J Cardiovasc Pharmacol 42(suppl) Pages: S61-S65
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Apoptosis induced by inhibition of cAMP responsive element binding protein in vascular smooth muscle cells. ^*co-first author. (2003)
  • Author(s): Tokunou T^*, Shibata R^*, Kai H, Ichiki T, Morisaki T, Iino N, Masuda S, Shimokawa H, Egashira K, Takeshita A.
  • Journal Title: Circulation 108(10) Pages: 1246-1252
  • Description: 「研究成果報告書概要(欧文)」より