A study of role of phospholipase A2 receptor in pathogenosis ofcardiovascular diseases and development of new drug for cardiovascular diseases

磷脂酶A2受体在心血管疾病发病机制中的作用研究及心血管疾病新药开发

• 批准号: 22390158
• 负责人: KUGIYAMA Kiyotaka
• 金额: $ 11.98万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390158/
• 关键词: 心筋梗塞; 炎症; 心血管病; ノックアウトマウス; 分泌型ホスホリパーゼA2受容体; ホスホリパーゼA2; 受容体; TNF

This study was aimed to examine a possible role of secretory PLA2receptor in the pathogenesis of cardiovascular diseases and to develop a new drug forprevention from cardiovascular diseases. As a result, (1) PLA2R－/－mice had a higherprevalence of cardiac rupture after MI compared with the PLA2R+/+mice. PLA2R－/－mice hada low content of collagen and a reduction in the number of myofibroblasts and theexpression of profibrogenic molecules in the infarct region. (2) The ovalbumin(OVA)-induced airway inflammation, characterized by an increased number of eosinophilsand neutrophils in BAL fluid and inflammatory histological changes in airway, was strongerin PLA2R－/－mice than in PLA2R+/+mice.

本研究旨在探讨分泌型PLA 2受体在心血管疾病发病机制中的可能作用，并开发新的预防心血管疾病的药物。结果表明：（1）与PLA 2 R +/+小鼠相比，PLA 2 R-/-小鼠MI后心脏破裂的发生率更高。PLA 2 R-/-小鼠梗死区胶原含量低，肌成纤维细胞数量减少，促纤维化分子表达减少。(2)卵清蛋白（OVA）诱导的气道炎症表现为支气管肺泡灌洗液中嗜酸性粒细胞和中性粒细胞数量的增加以及气道的炎性组织学改变，PLA 2 R-/-小鼠比PLA 2 R +/+小鼠更强。

项目成果

High plasma levels of macrophage migration inhibitory factor are associated with adverse long-term outcome in patients with stable coronary artery disease and impaired glucose tolerance or type 2 diabetes mellitus

• DOI: 10.1016/j.atherosclerosis.2010.09.004
• 发表时间: 2010-12-01
• 期刊: ATHEROSCLEROSIS
• 影响因子: 5.3
• 作者: Makino, Aritaka;Nakamura, Takamitsu;Kugiyama, Kiyotaka
• 通讯作者: Kugiyama, Kiyotaka

Group X secretory PLA2 in neutrophils plays a pathogenic role in abdominal aortic aneurysms in mice

中性粒细胞中 X 族分泌型 PLA2 在小鼠腹主动脉瘤中发挥致病作用

• DOI: 10.1152/ajpheart.00695.2011
• 发表时间: 2012
• 期刊: Am J Physiol Heart Circ Physiol
• 作者: Watanabe K;et al
• 通讯作者: et al

Chronic Depletion of GlutathioneExacerbates Ventricular Remodeling andDysfunction in Pressure Overloaded Heartin Mice Lacking the Glutamate-CysteineLigase Modifier Subunit

慢性消耗谷胱甘肽会加剧缺乏谷氨酸-半胱氨酸连接酶修饰亚基的压力超载心脏小鼠的心室重塑和功能障碍

• 发表时间: 2012
• 作者: Yosuke Watanabe,Kazuhiro Watanabe;Tsuyoshi Kobayashi,Yukio Saito;Daisuke Fujioka;TakamitsuNakamura;Jun-ei Obata;Kenichi Kawabata,Hideto Mishina;and Kiyotaka Kugiyama
• 通讯作者: and Kiyotaka Kugiyama

Inhibition of Secretory Phospholipase A2 Activity Attenuates Acute Cardiogenic Pulmonary Edema Induced by Isoproterenol Infusion in Mice After Myocardial Infarction

• DOI: 10.1097/fjc.0b013e3181ef1aab
• 发表时间: 2010-10-01
• 期刊: JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
• 影响因子: 3
• 作者: Kawabata, Kenichi;Fujioka, Daisuke;Kugiyama, Kiyotaka
• 通讯作者: Kugiyama, Kiyotaka

Group V secretory phospholipase A2 plays a pathogenic role in myocardial ischaemia-reperfusion injury.

• DOI: 10.1093/cvr/cvq399
• 发表时间: 2011-05
• 期刊: Cardiovascular research
• 影响因子: 10.8
• 作者: T. Yano;Daisuke Fujioka;Yukio Saito;Tsuyoshi Kobayashi;Takamitsu Nakamura;J. Obata;K. Kawabata;Kazuhiro Watanabe;Yosuke Watanabe;Hideto Mishina;Shun Tamaru;K. Kugiyama