ROLE OF ANGIOTENSIN II IN SKELETAL MUSCLE HYPERTROPHY

血管紧张素 II 在骨骼肌肥大中的作用

• 批准号: 6403161
• 负责人: SCOTT E GORDON
• 金额: $ 1.32万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6403161
• 关键词: ACE inhibitors; actins; angiotensin II; angiotensin receptor; angiotensinogen; focal adhesion kinase; gene induction /repression; genetic promoter element; immunocytochemistry; laboratory rat; messenger RNA; muscle hypertrophy; muscle pharmacology; oral administration; peptidyl dipeptidase A; polymerase chain reaction; striated muscles; western blottings

Promoting skeletal muscle growth is extremely relevant to medical conditions in which muscle wasting contributes to low quality of life and high health care costs due to institutionalization. The proposed research would explore the possibility that angiotensin II (AII) positively mediates loading-induced skeletal muscle hypertrophy. This phenomenon occurs in cardiac muscle, but would be a completely novel finding in skeletal muscle tissue. Using the synergist ablation model of skeletal muscle hypertrophy in rats, the present experiment would determine if: 1) AII peptide and its precursors are up-regulated in skeletal muscle in response to increased loading, 2) inhibition of AII production by inhibiting angiotensin converting enzyme (ACE) prevents loading-induced skeletal muscle hypertrophy, and 3) AII receptors are present in skeletal muscle. Promising pilot data indicate that ACE inhibition may attenuate hypertrophy by at least 46 percent in this model. It is also proposed to measure an AII-responsive intracellular signaling pathway involving focal adhesion kinase and serum response factor, both of which are also necessary for loading-induced skeletal muscle hypertrophy. Identification of novel hormonal mechanisms promoting skeletal muscle growth may lead to drugs, gene medicine, or other countermeasures against skeletal muscle wasting.

促进骨骼肌肉生长与医疗状况极为相关，在这种情况下，由于制度化，肌肉浪费有助于较低的生活质量和高医疗保健成本。 拟议的研究将探讨血管紧张素II（AII）积极介导负荷诱导的骨骼肌肥大的可能性。 这种现象发生在心肌中，但在骨骼肌组织中是一个完全新颖的发现。 利用大鼠骨骼肌肥大的协同消融模型，本实验将确定：1）AII肽及其前体在骨骼肌中响应增加的负荷而在骨骼肌中上调，2）通过抑制AII的产生，通过抑制了固定酶（ACE）的固定酶（ACE）的固定剂，并抑制了骨骼感应的骨骼肌肉素（ACE），肌肉素（ACE）的骨骼感应型骨骼感应的骨骼感染者，骨骼肌肉均受到抑制作用。骨骼肌。 有希望的飞行员数据表明​​，在该模型中，ACE抑制可能至少减轻46％的肥大。 还建议测量涉及局灶性粘附激酶和血清反应因子的AII响应性细胞内信号传导途径，这两种途径对于负载诱导的骨骼肌肥大也是必需的。鉴定促进骨骼肌生长的新型激素机制可能导致药物，基因医学或其他针对骨骼肌浪费的对策。