Identification of a novel gene to promote atherosclerosis development by regulating fatty acid binding protein secreted from dysfunctional kidney
| Project/Area Number |
21590957
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
YAMADA Hiroyuki 京都府立医科大学, 医学研究科, 助教 (00240036)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 血管病態学 / 動脈硬化 / 慢性腎臓病 / 脂肪組織 / レニン・アンジオテンシン系 / 脂肪酸代謝 / 脂肪酸結合蛋白 |
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| Research Abstract |
In this study, we demonstrated for the first time that exaggerated atherosclerosis development elicited by uninephrectomy was closely associated with PAT-specific increases in AGT mRNA expression and Ang II secretion without enhanced recruitment of monocytes/macrophages. HOMA-IR index and plasma insulin concentrations after glucose loading were markedly elevated in uninephrectomized apoE^<-/-> mice, and insulin stimulation of isolated PAT mature adipocytes significantly increased AGT mRNA expression in a depot-specific manner, suggesting that insulin resistance-associated hyperinsulinemia most likely contributed to the PAT-specific activation of RAS. In contrast, expression of adhesion molecules in the vasculature and the number of circulating inflammatory monocytes, which played a crucial role in the early stage of atherosclerosis development, were not altered by uninephrectomy. Moreover, accelerated atherosclerosis development caused by uninephrectomy was completely inhibited in apoE^<-/->/AT1aR^<-/-> mice or by treatment with angiotensin II type 1 receptor blocker(olmesartan), further supporting the notion that PAT-specific activation of RAS is substantially involved in the CKD-associated atherogenesis and could be a novel therapeutic target for the prevention of CKD-associated cardiovascular disease.
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Report
(4 results)
Research Products
(35 results)
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[Journal Article] Bone Marrow AT_1 Augments Neointima Formation by Promoting Mobilization of Smooth Muscle Progenitors via Platelet-Derived SDF-1α2010
Author(s)
Yokoi H, Yamada H, Tsubakimoto Y, Takata H, Kawahito H, Kishida S, Taku Kato T, Akihiro Matsui A, Hideyo Hirai H, Eishi Ashihara E, Taira Maekawa T, Masaru Iwai M, Masatsugu Horiuchi M, Kouji Ikeda K, Tomosaburo Takahashi T, Mitsuhiko Okigaki M, and Hiroaki Matsubara H
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Journal Title
Arterioscler Thromb Vasc Biol
Volume: 30
Pages: 60-67
Related Report
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[Journal Article] Bone Marrow Angiotensin AT_1 Receptor Regulates Differentiation of Monocyte Lineage Progenitors from Hematopoietic Stem Cells2009
Author(s)
Tsubakimoto Y, Yamada H, Yokoi H, Kishida S, Takata H, Kawahito H, Matsui A, Urao N, Nozawa Y, Hirai H, Imanishi J, Ashihara E, Maekawa T, Takahashi T, Okigaki M, Hiroaki Matsubara H
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Journal Title
Arterioscler Thromb Vasc Biol
Volume: 29
Pages: 1529-1536
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[Presentation] Phenotypic conversion of brown to white perivascular adipose tissue in uninephrectomized apoE deficient mice : Possible role in the early stage of atherosclerosis in chronic kidney disease2011
Author(s)
Kawahito H, Yamada H, Kishida S, Kato T, Irie D, Fukui K, Ikeda K, Okigaki M, Mori M, Matsubara H
Organizer
American Heart Association(米国心臓病学術会議)
Place of Presentation
Orland, USA
Related Report
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[Presentation] Bone marrow angiotensin AT2 receptor deficiency aggravates atherosclerosis by eliminating macrophage liver X receptor-mediated anti-atherogenic actions2011
Author(s)
Kato T, Yamada H, Kawahito H, Irie D, Fukui K, Ikeda K, Okigaki M, Mogi M, Iwai M, Horiuchi M, Matsubara H
Organizer
American Heart Association(米国心臓病学術会議)
Place of Presentation
Orland, USA
Related Report
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[Presentation] Bone marrow angiotensin AT_1 receptor regulates differentiation of Monocyte lineage progenitors from hematopoietic stem cells2010
Author(s)
Yamada H, Tsubakimoto Y, Yokoi H, Kishida S, Kato T, Kawahito H, Hirai H, Ashihara E, Maekawa T, Ikeda K, Takahashi T, Okigaki M, Matsubara H
Organizer
International Congress of Endocrinology(ICE)
Place of Presentation
Kyoto, Japan
Related Report
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[Presentation] Bone marrow AT_1 augments neointima formation by promoting mobilization of smooth muscle progenitors via platelet-derived SDF-1α2010
Author(s)
Yamada H, Tsubakimoto Y, Yokoi H, Kishida S, Kato T, Kawahito H, Hirai H, Ashihara E, Maekawa T, Iwai M, Horiuchi M, Ikeda K, Takahashi T, Okigaki M, Matsubara H
Organizer
International Congress of Endocrinology(ICE)
Place of Presentation
Kyoto, Japan
Related Report
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