Estrogen receptor alpha are predominantly involved in heart VEGF pathway in diabetic female mice.

• Project/Area Number: 25462600
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Ibaraki Prefectural University of Health Science
• Principal Investigator: Yamaguchi Naoto 茨城県立医療大学, 保健医療学部, 教授 (40239900)
• Co-Investigator(Kenkyū-buntansha): ARAI Jesmin (ARAI Subrina) 筑波大学, 医学医療系, 助教 (60374261)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 糖尿病 / 血管内皮増殖因子 / エストロゲン受容体 / 閉経 / 心不全 / マウス / 心臓組織 / 閉経後 / VEGF / 微小循環異常

Outline of Final Research Achievements

We have previously demonstrated that vascular endothelial growth factor (VEGF) is critical for heart tissue (coronary) microvascular angiogenesis in diabetes. Here we attempt to elucidate the effects of estrogen and its specific receptor (ER) subtype in heart tissue VEGF pathways and microvascular angiogenesis using 15-week female mice that are either wild-type (WT), lack of ER alpha (ER alpha KO) or beta (ER beta KO), all of them have diabetes induced by streptozotocin. Cardiac function was reduced and VEGF expression was down-regulated in both ER alpha KO and ER beta KO mice, especially in ER alpha KO mice, compared to WT. These findings suggest that ER alpha are predominantly involved in the pathogenesis of diabetic heart failure through down-regulation of tissue VEGF pathway.

Research Products

• [Journal Article] Effects of diabetes on cardiac VEGF system in estrogen/estrogen receptor manipulated animal model. (2015)
  • Author(s): Jesmin S, Mamun AA, rahman MA, Islam MM, Shimojo N, Sultana SN, Yamaguchi N.
  • Journal Title: Diabetes Research and Clinical Practice Volume: 106 Pages: 54-55
  • Acknowledgement Compliant
• [Journal Article] Nationwide prevalence, awareness, treatment and control of hypertension among the adult population in Bangladesh. (2015)
  • Author(s): Jesmin S, Iwashima Y, Rahman MAS, Yamaguchi N, Kawano S, Kawano Y.
  • Journal Title: European Heart Journl Volume: ３６ Pages: 897-897
  • Acknowledgement Compliant
• [Journal Article] Assessment of circulatory levels of edothelin-1 in diabetic subjects screened through a cross sectional study from rural women in Bangladesh. (2015)
  • Author(s): Rahman MA, Jesmin S, Mowa CN, Kamiyama J, Shimojo N, Islam MM, Moroi M, Okazaki O, Yamaguchi N, Kawano S, Mizutani T, Iwashima Y.
  • Journal Title: International Journal of Diabetes and Clinical Research Volume: 2 Pages: 1-5
  • Acknowledgement Compliant
• [Journal Article] Effects of protease activated receptor (PAR) 2 blocking peptide on endothelin-1 levels in kidney tissues in endotoxemic rat model (2014)
  • Author(s): Jesmin S, Shimojo N, Yamaguchi N, et al
  • Journal Title: Life Sci Volume: 102(2) Issue: 2 Pages: 127-33
  • DOI: 10.1016/j.lfs.2014.03.013
  • Peer Reviewed / Open Access
• [Journal Article] Higher gravidity and parity are associated with increased prevalence of metabolic syndrome among rural Bangladeshi women (2013)
  • Author(s): Akter S, Jesmin S, Rahman MM, Islam MM, Khatun MT, Yamaguchi N, Akashi H, Mizutani T
  • Journal Title: PLoS One Volume: 8(8) Issue: 8 Pages: 1-8
  • DOI: 10.1371/journal.pone.0068319
  • NAID: 120007136818
  • Peer Reviewed
• [Journal Article] Metabolic syndrome among pre- and post-menopausal rural women in Bangladesh: result from a population-based study (2013)
  • Author(s): Jesmin S, Islam AS, Akter S, Islam MM, Sultana SN, Yamaguchi N, et al.
  • Journal Title: BMC Res Notes. PMID: 23597398 Volume: 6(1):157 Pages: 1-5
  • Peer Reviewed
• [Presentation] Nationwide prevalence, awareness, treatment and control of hypertension among the adult population in Bangladesh. (2015)
  • Author(s): Jesmin S, Iwashima Y, Rahman MA, Habib AKMA, Shimojo N, Moroi M, Yamaguchi N, Okazaki O, kawano Y.
  • Organizer: ESC Congress 2015.
  • Place of Presentation: London , UK.
  • Year and Date: 2015-08-29
  • Int'l Joint Research
• [Presentation] nationwide non-communicable disease risk factors profile in Bangladesh. (2015)
  • Author(s): Rahman MA, Jesmin S, Islam MM, Sultana SN, Khatun T, Yamaguchi N, Okazaki O, Iswashima Y, Kawano S.
  • Organizer: Te 11th Asian Pacitic Congress of Hypertension (APCH 2015)
  • Place of Presentation: Bali, Indonesia.
  • Year and Date: 2015-06-04
  • Int'l Joint Research
• [Presentation] dual endothelin antagonism from early diabetic stage is effective in preventing various diabetic complications through both improving organ microcirculation and restoration of altered VEGF signaling. (2013)
  • Author(s): Jesmin S, Shimojo N, Sultana SN, Islam M, Kawano S, mizutani T, Miyauchi T.
  • Organizer: Thirteenth International conference on endothelin.
  • Place of Presentation: 筑波大学東京
• [Book] Chapter 12: Development of therapeutic strategy to restore coronary microcirculation and vascular endothelial growth factor signaling cascade in diabetes mellitus. A holostic approach to diagnosis and treatment. In Diabetes mellitus and human health care, edited by George A, Augustine R. (2013)
  • Author(s): Jesmin S, Rahman A, Manum AA, Akter S, Iwashima Y, Shimojo N, Yamaguchi N, Hiroaki M, Mizutani T, Moroi M,
  • Publisher: CBC Press: ISBN 978-19268-95765