2013 Fiscal Year Final Research Report
The molecular mechanism of atherosclerosis through endothelial dysfunction
Project/Area Number |
23591101
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
|
Research Institution | Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses (2013) Osaka University (2011-2012) |
Principal Investigator |
KURODA TADASHI 地方独立行政法人大阪府立病院機構大阪府立成人病センター(研究所), その他部局等, その他(副部長) (60403078)
|
Co-Investigator(Kenkyū-buntansha) |
NAKAOKA Yoshikazu 大阪大学, 医学(系)研究科(研究院), 助教 (90393214)
|
Project Period (FY) |
2011 – 2013
|
Keywords | 動脈硬化 / 血管炎症 / 内皮 / Gab1 / KLF2 |
Research Abstract |
We reported that Gab1 is essential for postnatal angiogenesis through the analysis of endothelium-specific Gab1 knockout (Gab1ECKO) mice. However, the role of Gab1 in atherosclerosis remains unknown. We intercrossed Gab1ECKO mice with ApoE knockout (ApoEKO) mice. Six-month-old male ApoEKO/Gab1ECKO and littermate control (ApoEKO) mice were treated with angiotensin II (AngII) via an osmotic infusion minipump. After AngII treatment, ApoEKO/Gab1ECKO mice showed significantly enhanced atherosclerosis and aneurysm formation compared with control mice. The production of proinflammatory cytokines in the aorta was significantly enhanced in ApoEKO/Gab1ECKO mice compared with control. The expression levels of KLF2 and KLF4 were significantly reduced in the aortic endothelium of ApoEKO/Gab1ECKO mice compared with control. Collectively, endothelial Gab1 deletion accelerates AngII-dependent vascular inflammation and atherosclerosis presumably via downregulation of KLF2 and KLF4.
|
-
[Journal Article] A novel homemade snare, safe, economical and size adjustable2014
Author(s)
Yokoi K, Sumitsuji S, Kaneda H, Siegrist P, Okayama K, Ide S, Mizote I, Kumada M, Kuroda T, Tachibana K, Sakata Y, Nanto S
-
Journal Title
EuroIntervention
Volume: (Epub ahead of print)
Pages: 20130208-01
Peer Reviewed
-
[Journal Article] Angiopoietin-1 guides directional angiogenesis through integrinαvβ5 signaling for recovery of ischemic retinopathy2013
Author(s)
Lee J, Kim KE, Choi DK, Jang JY, Jung JJ, Kiyonari H, Shioi G, Chang W, Suda T, Mochizuki N, Nakaoka Y, Komuro I, Yoo OJ, Koh GY
-
Journal Title
Sci Transl Med
Volume: 5(203)
Pages: 203ra127
DOI
Peer Reviewed
-
[Journal Article] Tocilizumab for the Treatment of the Patients with Refractory Takayasu Arteritis2013
Author(s)
Nakaoka Y, Higuchi K, Arita Y, Otsuki M, Yamamoto K, Hashimoto-Kataoka T, Yasui T, Ikeoka K, Ohtani T, Sakata Y, Shima Y, Kumanogoh A, Yamauchi-Takihara K, Tanaka T, Kishimoto T, Komuro I
-
Journal Title
Int Heart J
Volume: 54
Pages: 405-411
Peer Reviewed
-
-
[Journal Article] Alpha-synuclein elicits glucose uptake and utilization in adipocytes through the Gab1/PI3K/Akt transduction pathway2013
Author(s)
Rodriguez-Araujo G, Nakagami H, Hayashi H, Mori M, Shiuchi T, Minokoshi Y, Nakaoka Y, Takami Y, Komuro I, Morishita R, Kaneda Y
-
Journal Title
Cell Mol Life Sci
Volume: 70(6)
Pages: 1123-33
DOI
Peer Reviewed
-
-
-
-
[Journal Article] Endothelial Gab1 deletion accelerates angiotensin II-dependent vascular inflammation and atherosclerosis in apolipoprotein E knockout mice2012
Author(s)
Higuchi K, Nakaoka Y, Shioyama W, Arita Y, Hashimoto T, Yasui T, Ikeoka K, Kuroda T, Minami T, Nishida K, Fujio Y, Yamauchi-Takihara K, Shirai M, Mochizuki N, Komuro I
-
Journal Title
Circ J
Volume: 76
Pages: 2031-40
DOI
Peer Reviewed
-
[Journal Article] Maximum carotid intima-media thickness improves the prediction ability of coronary artery stenosis in type 2 diabetic patients without history of coronary artery disease2012
Author(s)
Irie Y, Katakami N, Kaneto H, Kasami R, Sumitsuji S, Yamasaki K, Tachibana K, Kuroda T, Sakamoto K, Umayahara Y, Ueda Y, Kosugi K, Shimomura I
-
Journal Title
Atherosclerosis
Volume: 221(2)
Pages: 438-44
DOI
Peer Reviewed
-
-
[Journal Article] Gab1 is essential for postnatal angiogenesis via hepatocyte growth factor/c-Met signaling2011
Author(s)
Shioyama W, Nakaoka Y, Higuchi K, Minami T, Taniyama Y, Nishida K, Kidoya H, Sonobe T, Naito H, Arita Y, Hashimoto T, Kuroda T, Fujio Y, Shirai M, Takakura N, Morishita R, Yamauchi-Takihara K, Kodama T, Hirano T, Mochizuki N, Komuro I
-
Journal Title
Circ Res
Volume: 108
Pages: 664-675
DOI
Peer Reviewed
-
[Presentation] Blockade of interleukin-6 signaling prevents hypoxia induced pulmonary hypertension in mice2013
Author(s)
Hashimoto-Kataoka T, Nakaoka Y, Sonobe T, Higuchi K, Arita Y, Yasui T, Ikeoka K, Masaki T, Yamauchi-Takihara K, Shirai M, Komuro I
Organizer
American Heart Association Scientific Sessions 2013
Place of Presentation
Dallas Convention Center (アメリカ合衆国・ダラス)
Year and Date
2013-11-17
-
-
-
-
-
-
-
[Presentation] Angiopoietin-1 secreted from myocardium is essential for the formation of coronary veins in the developing heart2013
Author(s)
Arita Y, Nakaoka Y, Matsunaga T, Kidoya H, Yamamizu K, Arima Y, Higuchi K, Hashimoto T, Ikeoka K, Yasui T, Nishiyama K, Kurihara H, Yamauchi-Takihara K, Yamagishi H, Takakura N, Mochizuki N, Koh GY, Komuro I
Organizer
第30回国際心臓研究学会(ISHR)日本部会総会
Place of Presentation
La Valencia Hotel(アメリカ合衆国・サンディエゴ)
Year and Date
2013-06-29
-
-
-
-
-
[Presentation] Gab1 Negatively regulates Angiotensin II-accelerated Atherosclerosis in Apolipoprotein E Deficient Mice2011
Author(s)
Nakaoka Y, Higuchi K, Shioyama W, Taniyama Y, Arita Y, Hashimoto T, Fujio Y, Yamauchi-Takihara K, Morishita R, Hirano T, Komuro I
Organizer
第75回日本循環器学会学術集会
Place of Presentation
パシフィコ横浜(横浜市)
Year and Date
2011-08-04
-
-
-