2006 Fiscal Year Final Research Report Summary
Analysis of the mechanisms for antiatherogenic effect of bone marrow AT2 receptor by using gene-targeted mice
| Project/Area Number |
17590760
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Kyoto Prefectural University of Medicine |
|---|
Principal Investigator |
YAMADA Hiroyuki Kyoto Prefectural University of Medicine, Graduate School of Medicine, Assistant Professor, 医学研究科, 助教 (00240036)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MATSUBARA Hiroaki Kyoto Prefectural University of Medicine, Graduate School of Medicine, Professor, 医学研究科, 教授 (10239072)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Keywords | angiotensin II / atherosclerosis / bone marrow cells / progenitors / receptors |
|---|
| Research Abstract |
Objective : The angiotensin II (Ang II) type 1 (AT_1) and type 2 (AT_2) receptor play a key roles in atherogenesis ; however, bone marrow (BM) AT_1 and AT_2-mediated actions remain undefined. The purpose of this study was to elucidate the effect of BM-AT_1 and BM-AT_2 on the pathogenesis of atherosclerosis development and vascular repair.
Methods and Results : (1) Atherosclerosis model ; ApoE-KO mice reconstituted with Agtrl^<-/->marrow (apoE-KO/BM-Agtrl^<-/->) showed a significant reduction in atherosclerotic lesions compared with apoE-KO/BM-Agtrl^<+/+> mice. The accumulation of monocytes/macrophages was attenuated in apoE-KO/BM-Agtrl^<-/->mice, concomitant with a decrease in the number of circulating Ly-6C^<hi> monocytes. Flow cytometric analysis of BM cells showed that the number of granulocyte/macrophage progenitors was much lower in apoE-KO/BM-Agtrl^<-/->mice, whereas the number of hematopoietic stem cells (HSCs) did not differ between the two groups, suggesting that BM-AT_1 promot
… More
es the transition from HSCs to macrophage progenitors. (2) Vascular repair model ; Total BM cells from Agtr1^<-/->, Agtr2^<-/->, or WT mice were transplanted into BM-ablated WT and femoral arterial injury was performed. Neointimal formation was markedly increased in BM-Agtr2^<-/->compared with BM-WT mice, whereas it was much lower in BM-Agtrl^<-/->mice. Circulating potential vascular progenitor cells, defined by c-kit-/lin-/Sca-1^+ markers, were markedly decreased in BM-Agtrl^<-/->mice, whereas CXR4^+ vascular progenitor cells markedly increased in BM-Agtr2^<-/->mice.
Conclusions : BM-AT_1 is closely implicated in the development of HSCs into macrophage progenitors and vascular progenitors, whereas BM-AT_2 is likely to modulate the property of monocyte/macrophage and vascular progenitors leading to the augmented mobilization from the bone marrow and accumulation at the site of vascular repair. Our study indicates that BM-AT_1 and BM-AT_2 could be a promising therapeutic target for the prevention of cardiovascular events. Less
|
Research Products
(16 results)
-
-
-
-
-
[Journal Article] Erythropoietin-Mobilized Endothelia Progenitors Enhance Reendothelialization via Akt-Endothelial Nitric Oxide Synthase Activation and Prevent Neointimal Hyperplasia.2006
Author(s)
Urao N, Okigaki M, Yamada H, Adachi Y, Matsuno K, Matsui A, Matsunaga S, Tateishi K, Nomura T, Takahashi T, Tatsumi T, Matsubara H.
-
Journal Title
Cir Res 98
Pages: 1405-1413
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
-
[Journal Article] Noxl Is Involved in Angiotensin II-Mediated Hypertension-A Study in Noxl-Deficient Mice.2005
Author(s)
Matsuno K, Yamada H, Iwata K, Jin D, Katsuyama M, Matsuki M, Takai S, Yamanishi K, Miyazaki M, Matsubara H, Yabe-Nishimura C.
-
Journal Title
Circulation 112
Pages: 2677-2685
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Book] THE ARB2006
Author(s)
山田浩之, 高田博輝, 勝目あさ子, 椿本恵則, 横井宏和, 松原弘明
Total Pages
487
Publisher
ARBの薬理作用 心臓リモデリング改善作用
Description
「研究成果報告書概要(和文)」より
