Role of inflammatory mechanism in the experimental model of pulmonary arterial hypertension

• Project/Area Number: 26461606
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Mie University
• Principal Investigator: Sawada Hirofumi 三重大学, 医学系研究科, 講師 (30362354)
• Co-Investigator(Kenkyū-buntansha): 丸山 一男 三重大学, 医学系研究科, 教授 (20181828) ; 三谷 義英 三重大学, 医学部附属病院, 准教授 (60273380)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肺高血圧 / 炎症 / サイトカイン / 炎症機序

Outline of Final Research Achievements

Although the role of BMPR2 mutation in the pathogenesis of pulmonary arterial hypertension (PAH) was not established, association of BMPR2 mutation and inflammatory mechanisms are shown in clinical and experimental pathology of PAH. We have shown that anti GM-CSF antibody administration improved the hypoxia induced pulmonary hypertension. To further elucidate the role of inflammation in PAH, we investigated the role of inflammation in a new human PAH-like rat model induced by the vascular endothelial growth factor receptor blockade with Sugen 5416 in combination with chronic hypoxia. Compared with in controls, the number of perivascular macrophages progressively increased during the experimental period; gene expression of IL6, MCP1, MMP9, cathepsin-S, and RANTES was distinctively upregulated in lungs.

Research Products

• [Journal Article] Loss of PPAR in endothelial cells leads to impaired angiogenesis. (2016)
  • Author(s): Vattulainen-Collanus S, Akinrinade O, Li M, Koskenvuo M, Li CG, Rao SP, de Jesus Perez V, Yuan K, Sawada H, Koskenvuo JW, Alvira C, Rabinovitch M, Alastalo TP.
  • Journal Title: J Cell Sci. Volume: 129 Pages: 693-705
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Comparative Transcriptome Analysis Identifies CCDC80 as a Novel Gene Associated with Pulmonary Arterial Hypertension. (2016)
  • Author(s): Yuhei Nishimura, Shota Sasagawa, Hirofumi Sawada, Erquan Zhang, Soichiro Murakami, Yoshifumi Ashikawa, Mizuki Yuge, Shiko Okabe, Koki Kawaguchi, Reiko Kawase, Yoshihide Mitani, Kazuo Maruyama, TOSHIO TANAKA.
  • Journal Title: Front. Pharmacol., Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] Loss of PPARγ in endothelial cells leads to impaired angiogenesis. (2016)
  • Author(s): Vattulainen-Collanus S, Akinrinade O, Li M, Koskenvuo M, Li CG, Rao SP, de Jesus Perez V, Yuan K, Sawada H, Koskenvuo JW, Alvira C, Rabinovitch M, Alastalo TP.
  • Journal Title: J Cell Sci. Volume: 129 Pages: 693-705
  • DOI: 10.1242/jcs.169011
  • Peer Reviewed
• [Journal Article] Sarpogrelate hydrochloride, a serotonin 5HT2A receptor antagonist, ameliorates the development of chronic hypoxic pulmonary hypertension in rats (2015)
  • Author(s): Zhang E, Maruyama J, et al.
  • Journal Title: J Anesth Volume: 29 Issue: 5 Pages: 715-723
  • DOI: 10.1007/s00540-015-2015-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Macitentan reverses early obstructive pulmonary vasculopathy in rats: early intervention in overcoming the survivin-mediated resistance to apoptosis. (2015)
  • Author(s): Shinohara T, Sawada H, Otsuki S, Yodoya N, Kato T, Ohashi H, Zhang E, Saitoh S, Shimpo H, Maruyama K, Komada Y, Mitani Y.
  • Journal Title: Am J Physiol Lung Cell Mol Physiol. Volume: 308(6) Issue: 6 Pages: L523-L538
  • DOI: 10.1152/ajplung.00129.2014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Potential Contribution of Phenotypically Modulated Smooth Muscle Cells and Related Inflammation in the Development of Experimental Obstructive Pulmonary Vasculopathy in Rats. (2015)
  • Author(s): Otsuki S, Sawada H, Yodoya N, Shinohara T, Kato T, Ohashi H, Zhang E, Imanaka-Yoshida K, Shimpo H, Maruyama K, Komada Y, Mitani Y.
  • Journal Title: PLoS One. Volume: 10 Issue: 2 Pages: 0118655-0118655
  • DOI: 10.1371/journal.pone.0118655
  • Peer Reviewed / Open Access