Elucidation of Effects of Oxidized Sterol Accumulation on the Progression of Diabetic Cardiomyopathy
Project/Area Number |
19K21324
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Project/Area Number (Other) |
18H06222 (2018)
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund (2019) Single-year Grants (2018) |
Review Section |
0903:Organ-based internal medicine and related fields
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Research Institution | Osaka University |
Principal Investigator |
Okada Takeshi 大阪大学, 医学系研究科, 寄附講座助教 (20750136)
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Project Period (FY) |
2018-08-24 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 糖尿病性心筋症 / 酸化ステロール / ミトコンドリア機能障害 / 心不全 |
Outline of Research at the Start |
糖尿病性心筋症は糖尿病性心不全の前段階と考えられ、心筋肥大と拡張機能不全を特徴とするが、詳細な発症メカニズムは明らかでない。糖尿病では腸管の脂質吸収が亢進していると考えられており、また糖尿病患者では血中の酸化ステロール濃度が増加していることが報告されている。糖尿病性心筋症の増悪因子として酸化ステロールが関与している可能性について、動物モデルを用いて検討し、病態進展における酸化ステロール蓄積の役割を明らかにする。
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Outline of Final Research Achievements |
The purpose of this study is to investigate the effect of long-term absorption of a small amount of dietary oxidized sterols on myocardial tissue as a mechanism for the development of diabetic cardiomyopathy. We have prepared diets with and without oxidized sterols and fed them to streptozotocin-induced diabetic rats for 16 weeks. The rats fed the diet with oxidized sterols showed lower value of left ventricular strain on cardiac MRI, suggesting regional myocardial dysfunction. Moreover, mRNA expression of inflammatory cytokines was enhanced in the heart, and infiltration of inflammatory cells into myocardial tissue was observed in these rats. We will continue to evaluate the localization of oxidized sterols in myocardial tissue and elucidate the mechanism focusing on immune system cells or mitochondrial function.
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Academic Significance and Societal Importance of the Research Achievements |
本邦において糖尿病患者数は増加の一途を辿っている。糖尿病の合併により心不全発症リスクは高まるが、その前段階として心筋肥大や拡張機能不全を特徴とする糖尿病性心筋症がある。しかしこれまで、糖尿病性心筋症において何が増悪因子なのか、どの病態を改善すれば進展を阻止できるのか、詳細な分子メカニズムは明らかでない。糖尿病では腸管の脂質吸収が亢進しており、食事由来成分である酸化ステロールが糖尿病性心筋症を進展させる可能性を着想し、動物モデルを用いて再現した。酸化ステロールの新たなエビデンスが集積されることで、酸化ステロールに対する介入という新規治療法の開発につながる可能性がある。
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Report
(3 results)
Research Products
(9 results)
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[Journal Article] Progranulin deficiency leads to enhanced age-related cardiac hypertrophy through complement C1q-induced β-catenin activation.2020
Author(s)
Zhu Y, Ohama T, Kawase R, Chang J, Inui H, Kanno K, Okada T, Masuda D, Koseki M, Nishida M, Sakata Y, Yamashita S.
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Journal Title
Journal of Molecular and Cellular Cardiology
Volume: 138
Pages: 197-211
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Rivaroxaban Suppresses the Progression of Ischemic Cardiomyopathy in a Murine Model of Diet-Induced Myocardial Infarction2019
Author(s)
Liu J, Nishida M, Inui H, Chang J, Zhu Y, Kanno K, Matsuda H, Sairyo M, Okada T, Nakaoka H, Ohama T, Masuda D, Koseki M, Yamashita S, Sakata Y.
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Journal Title
Journal of Atherosclerosis and Thrombosis
Volume: 26
Issue: 10
Pages: 915-930
DOI
NAID
ISSN
1340-3478, 1880-3873
Year and Date
2019-10-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] Shotgun proteomic analysis reveals proteome alterations in HDL of patients with cholesteryl ester transfer protein deficiency.2019
Author(s)
Okada T, Ohama T, Takafuji K, Kanno K, Matsuda H, Sairyo M, Zhu Y, Saga A, Kobayashi T, Masuda D, Koseki M, Nishida M, Sakata Y, Yamashita S.
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Journal Title
J Clin Lipidol
Volume: 印刷中
Issue: 2
Pages: 317-325
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Prevalence of Coronary Artery Disease and Achievement of Low-density Lipoprotein Cholesterol Management Targets in Familial Hypercholesterolemia Patients at Osaka University Hospital2019
Author(s)
Takeshi Okada, Masahiro Koseki, Kotaro Kanno, Hiroyasu Inui, Jiuyang Chang, Yinghong Zhu, Ayami Saga, Masumi Asaji, Tohru Ohama, Makoto Nishida, Shizuya Yamashita, Yasushi Sakata
Organizer
第36回国際心臓研究学会日本部会
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