MOLECULAR MECHANISUMS OF CARDIOVASCULAR REMODELING

心血管重塑的分子机制

• 批准号: 09470527
• 负责人: IWAO Hiroshi
• 金额: $ 3.01万
• 依托单位: OSAKA CITY UNIVERSITY MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470527/
• 关键词: RENIN-ANGIOTENSIN SYSTEM; SIGNAL TRANSDUCTION; ORGA DAMAGE; MAP KINASE; CARDLAC HYPERTROPHY; ANGIOTENSIN RECEPTOR ANTAGONIST; CONVERTING ENZYME INHIBITOR; 心肥大

The renin-angiotensin-aldosterone system (RAAS) plays an important role in both the physiological regulation of blood pressure and in the pathophysiological disruption of cardiovascular organ damages. Angiotensin II (Ang II) is the primary biological mediator of the RAAS. Pathophysiological actions of Ang II is mediated by the angiotensin II type I receptor, for examples of vasoconstriction on vascular smooth muscle, secretion of aldosterone, reabsorption of sodium in the renal proximal nephron, and cell growth and proliferation.Treatments of RAAS inhibitors, angiotensin converting enzyme and Ang II type I receptor antagonist, in hypertensive rat models caused prevention effects of hypertension, cardiac hypertrophy, and vascular sclerosis and glomerular sclerosis. In addition, these effects were associated with suppressive gene expressions of TGF-b, collagen type I, collagen type II, fibronectin. These gene expression were caused by the stimulation of Ang II type I receptor through the activation of mitogen-activated protein kinases (ERK and JNK). Both angiotensin converting enzyme and Ang II type I receptor antagonist inhibited the activation of ERK and JNK.

肾素-血管紧张素-醛固酮系统（RAAS）在血压的生理调节和心血管器官损伤的病理生理破坏中起重要作用。血管紧张素II （Ang II）是RAAS的主要生物介质。Ang II的病理生理作用是由血管紧张素II型受体介导的，例如血管平滑肌的血管收缩、醛固酮的分泌、肾近端肾元钠的重吸收以及细胞的生长和增殖。RAAS抑制剂、血管紧张素转换酶和Ang II型受体拮抗剂对高血压大鼠模型有预防高血压、心肌肥厚、血管硬化和肾小球硬化的作用。此外，这些作用与TGF-b、I型胶原、II型胶原、纤维连接蛋白的抑制基因表达有关。这些基因表达是通过激活丝裂原活化蛋白激酶（ERK和JNK）刺激Ang II型I受体引起的。血管紧张素转换酶和Ang II型受体拮抗剂均抑制ERK和JNK的激活。

项目成果

S. Kim and H. Iwao: "Molecular and cellular mechamisms of Angiotensin II-Mediated cardiovascular and renal diseases"Pharmacological Reviews. 52. 11-34 (2000)

S. Kim 和 H. Iwao：“血管紧张素 II 介导的心血管和肾脏疾病的分子和细胞机制”药理学评论。

Hamaguchi,A., Kim,S., Wanibuchi,H. and Iwao, H.: "Imidapril inhibits increased transforming growth factor- β1 expression in remnant kidney model"European Journal of Pharmacology. 331. 27-30 (1997)

Hamaguchi, A.、Kim, S.、Wanibuchi, H. 和 Iwao, H.：“咪达普利抑制残肾模型中转化生长因子 - β1 表达的增加”欧洲药理学杂志 331. 27-30 (1997)。

Kim,S and Iwao,H.: "Activation of mitogen-activated protein kinases in cardiovascular hypertrophy and remodeling"Jpn.J.Pharmacol.. 80. 97-102 (1999)

Kim,S 和 Iwao,H.：“心血管肥大和重塑中丝裂原激活蛋白激酶的激活”Jpn.J.Pharmacol.. 80. 97-102 (1999)

S.Kim and H.Iwao: "Involvment of angiotensin II in cardiovascular and renal injury:efforts of on AT-1 receptor antagonist on gene expression and the cellular phenotype." J.Hypertens.15(Suppl.6). S3-S7 (1998)

S.Kim 和 H.Iwao：“血管紧张素 II 参与心血管和肾脏损伤：AT-1 受体拮抗剂对基因表达和细胞表型的影响。”

S.Kim et al.: "Angiotensin blockade inhibits activation of mitogen-activated protein kinases in rat balloon-injured artery." Circulation. 97. 1731-1737 (1998)

S.Kim 等人：“血管紧张素阻断可抑制大鼠球囊损伤动脉中丝裂原激活蛋白激酶的激活。”