Induction of pulmonary hypertension by inflammatory stimuli in mice with genetically reduced BMPR2

BMPR2 基因减少的小鼠炎症刺激诱导肺动脉高压

• 批准号: 23591565
• 负责人: SAWADA Hirofumi
• 金额: $ 3.41万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591565/
• 关键词: 肺高血圧; 炎症

Role of BMPR2 mutation in the pathogenesis of pulmonary arterial hypertension (PAH) has not been established. The inflammatory mechanisms are shown to be involved in clinical and experimental pathology of PAH. This study was planned to clarify the association of inflammatory mechanisms and BMPR2 gene mutation in the context of pulmonary hypertension by using the genetically modified animal models. We administered TNF alpha to BMPR2 hetero knockout (+/-) mice or control mice and assessed pulmonary hypertension and vascular lesions. Twoweek administration of TNF alpha did not induce pulmonary hypertension nor pulmonary vascular disease in the BMPR2 (+/-) mice. GMCSF administration aggravated hypoxia induced pulmonary hypertension in wild type mice, and anti GMCSF antibody administration improved the hypoxia induced pulmonary hypertension. Thus, an association of inflammatory mechanisms induced by reduced BMPR2 with pulmonary hypertension was demonstrated using animal models.

BMPR2 突变在肺动脉高压 (PAH) 发病机制中的作用尚未确定。炎症机制被证明参与 PAH 的临床和实验病理学。本研究计划通过使用转基因动物模型来阐明肺动脉高压背景下炎症机制与 BMPR2 基因突变的关联。我们给 BMPR2 异源基因敲除 (+/-) 小鼠或对照小鼠施用 TNF α，并评估肺动脉高压和血管病变。两周给予 TNF α 不会诱发 BMPR2 (+/-) 小鼠的肺动脉高压或肺血管疾病。 GMCSF给药加重了野生型小鼠缺氧诱导的肺动脉高压，而抗GMCSF抗体给药改善了缺氧诱导的肺动脉高压。 因此，使用动物模型证明了 BMPR2 减少诱导的炎症机制与肺动脉高压之间的关联。

项目成果

Marlene Rabinovitch肺高血圧において、BMPR2減少から炎症細胞浸潤に至る機序

Marlene Rabinovitch 肺动脉高压导致BMPR2降低和炎症细胞浸润的机制

• 发表时间: 2013
• 作者: 澤田博文;三谷義英;大槻祥一郎;淀谷典子;大橋啓之;丸山一男;駒田美弘
• 通讯作者: 駒田美弘

Effect of thrombomodulin on the development of monocrotaline-induced pulmonary hypertension

• DOI: 10.1007/s00540-013-1663-z
• 发表时间: 2014-02
• 期刊: Journal of Anesthesia
• 影响因子: 2.8
• 作者: Yasuharu Yamada;J. Maruyama;Erquan Zhang;A. Okada;A. Yokochi;H. Sawada;Y. Mitani;Tatsuya Hayashi;Koji Suzuki;K. Maruyama

Early detection of pediatric idiopathic pulmonary arterial hypertension by school electrocardiography screening: a nationwide survey in Japan.

通过学校心电图筛查早期发现儿童特发性肺动脉高压：日本的一项全国性调查。

• 发表时间: 2013
• 作者: Sawada H;Mitani Y;Nakayama T;Fukushima H;Kogaki S;Igarashi T;Ichida F;Ono Y;Nakanishi T;Doi S;Ishikawa S;Matsushima M;Yamada O;Saji T.
• 通讯作者: Saji T.

Loss of adenomatous poliposis coli-α3 integrin interaction promotes endothelial apoptosis in mice and humans.

• DOI: 10.1161/circresaha.112.267849
• 发表时间: 2012-12-07
• 期刊: Circulation research
• 影响因子: 20.1
• 作者: de Jesus Perez VA;Yuan K;Orcholski ME;Sawada H;Zhao M;Li CG;Tojais NF;Nickel N;Rajagopalan V;Spiekerkoetter E;Wang L;Dutta R;Bernstein D;Rabinovitch M
• 通讯作者: Rabinovitch M

Phenotypic Modulation of Smooth Muscle Cells and Related Inflammation in the Development of Experimental Obstructive Pulmonary Vasculopathy in Rats.

大鼠实验性阻塞性肺血管病发生过程中平滑肌细胞的表型调节及相关炎症。

• 发表时间: 2013
• 作者: Otsuki S;Sawada H;Yodoya N;Shinohara T;Kato T;Ohashi H;Zhang E;Yoshida-Imanaka K;Shimpo H;Maruyama K;Komada Y;Mitani Y.
• 通讯作者: Mitani Y.