The epigenetic control in the vascular lesion formation of pulmonary hypertension.

• Project/Area Number: 24791057
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Mie University
• Principal Investigator: YODOYA Noriko 三重大学, 医学部附属病院, 助教 (40525367)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 肺高血圧 / エストロゲン / エピジェネティクス

Outline of Final Research Achievements

Recentrly, a new human pulmonary arterial hypertention (PAH)-like rat model, which mimic pulmonary vasculopathy in human PAH, was reported.Since estorogen has been implicated in the pathogenesis of PAH and epigenetic modification of gene expression, we examined the vascular lesion formation of PAH under the estrogen administration with the rats. In the group received the estrogen before exhibiting PAH, vascular lesions were suppressed, but not in the group received estrogen after exhibited PAH. We found that estrogen was involved in the pathogenesis of PAH and the timing of administration of estrogen was important.
We attempted to separate cultures of smooth muscle cells from each level of the lung vessel and established culture method. This enables the study of cell level to elucidate the pathogenesis mechanisms.

Research Products

• [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