ROLE OF ANGIOTENSIN II IN SKELETAL MUSCLE HYPERTROPHY

血管紧张素 II 在骨骼肌肥大中的作用

基本信息

批准号：
6062450
负责人：
SCOTT E GORDON
金额：
$ 3.75万
依托单位：
UNIVERSITY OF MISSOURI-COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-03-01 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/6062450
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

项目摘要

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.

促进骨骼肌生长与医疗状况极为相关，在这些医疗状况中，肌肉萎缩会导致生活质量低下，并且由于机构化而导致医疗费用高昂。拟议的研究将探讨血管紧张素 II (AII) 积极介导负荷引起的骨骼肌肥大的可能性。这种现象发生在心肌中，但在骨骼肌组织中将是一个全新的发现。使用大鼠骨骼肌肥大的增效消融模型，本实验将确定是否：1) AII 肽及其前体在骨骼肌中因负荷增加而上调，2) 通过抑制血管紧张素转换酶来抑制 AII 产生(ACE) 可防止负荷引起的骨骼肌肥大，3) AII 受体存在于骨骼肌中。有希望的试验数据表明，在该模型中，ACE 抑制可以使肥大减弱至少 46%。还建议测量涉及粘着斑激酶和血清反应因子的 AII 响应细胞内信号通路，这两者对于负荷诱导的骨骼肌肥大也是必需的。促进骨骼肌生长的新激素机制的鉴定可能会导致药物、基因医学或其他对抗骨骼肌萎缩的对策。