アクティブボード・２０１０年９月
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研究発表を行った学会；
(1) 2010 Keystone Symposia Advances in Molecular Mechanisms of Atherosclerosis.
　２０１０年　２月１２日〜１７日（Banff, Alberta, Canada）

(2) 第74回日本循環器学会総会・学術集会
　２０１０年　３月　５日〜７日（京都）

タイトル；Angiopoietin-like protein2 (Angptl2) promotes coronary endothelial dysfunction and atherosclerosis.
　
発表者；　堀尾　英治　氏
　　　（熊本大学　大学院生命科学研究部　分子遺伝学分野）

Abstract；
Chronic vascular inflammation in coronary artery plays crucial roles in pathogenesis of coronary artery disease (CAD) through causing endothelial dysfunction and the progression of coronary atherosclerosis. Recently, we reported that adipose tissue-derived Angptl2 is a key mediator linking obesity to adipose tissue inflammation and systemic insulin resistance (Cell Metabolism 2009). Since angptl2 is also secreted from endothelial cells, and promotes vascular inflammation via the integrin α5β1/Rac1/NF-κB pathway, we investigated whether Angptl2 cause the coronary endothelial dysfunction and atherosclerosis in CAD.
First, we compared circulating Angptl2 levels in 83 subjects with coronary endothelial dysfunction (CED) and 30 subjects with chest pain syndrome (CPS) of normal coronary endothelial function. We assessed coronary endothelial function by estimating the ratio of coronary blood flow in response to intracoronary injection of acetylcholine (ACh). Plasma Angptl2 concentrations were significantly higher in CED subjects than CPS (4.475ng/ml vs 3.550ng/ml, p=0.0028). The increase of coronary blood flow after 20μg ACh injection was negatively correlated with plasma Angptl2 levels (r=-0.276, p=0.0154), but not with serum high sensitive CRP levels.
We next examined what cells express Angptl2 in coronary atherosclerosis by immunohistochemistry in human coronary athrosclerosis obtained from 10 autopsy cases.
Immunohistochemical analysis revealed that Angptl2 was abundantly expressed in endothelial cells, macrophages, and weakly in smooth muscle cells in atheromatous plaques.
Subsequently, we examined whether Angptl2 might contribute to the progression of atherosclerosis by cuff-induced vascular injury model in mouse femoral arteries. At 28 days after the surgery, neointimal hyperplasia in Angptl2-deficient mice was significantly attenuated compared to wild type mice (I/M ratio 0.264 vs. 0.155, p=0.0095).
These results suggested that Angptl2 might cause the vascular inflammation, resulting in coronary endothelial dysfunction and the progression of atherosclerosis. Suppression of Angptl2 might be a potential strategy for developing new effective therapies against atherosclerotic cardiovascular disease.