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Induction of ACE2 expression in skeletal muscles in aged mice by transcutaneous electrical stimulation

经皮电刺激诱导老年小鼠骨骼肌ACE2表达

基本信息

批准号：
9181102
负责人：
Yifan Li
金额：
$ 7.27万
依托单位：
UNIVERSITY OF SOUTH DAKOTA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9181102
关键词：
Accounting Age Aging Aging-Related Process Angiotensin II Angiotensin II Receptor Angiotensin-Converting Enzyme Inhibitors Cardiac Cardiovascular Diseases Cardiovascular system Chemicals Data Disease Female Foundations Functional disorder Future Gene Expression Goals Heart Homologous Gene Immunohistochemistry Inflammation Inflammatory Insulin Resistance Investigation Kidney Lentivirus Vector Longevity Methods Mitochondria Mus Muscle Muscle Contraction Muscle function Muscular Dystrophies Oxidative Stress Peptidyl-Dipeptidase A Peripheral Physiological Plasma Play Production Proteins Regulation Renin-Angiotensin System Reverse Transcriptase Polymerase Chain Reaction Role Skeletal Muscle Smooth Muscle Myocytes Source Staining method Stains System Testing Therapeutic Tissue Sample Transcutaneous Electric Nerve Stimulation Vascular Endothelial Cell Western Blotting age effect age related aged anti aging base kidney vascular structure male novel novel strategies novel therapeutic intervention prevent promoter research study response sciatic nerve skeletal small hairpin RNA

项目摘要

Angiotensin II (Ang II) plays a detrimental role in aging and aging related diseases. Inhibitions of Ang II production and activities have shown various anti-aging effects. Ang II is produced from Ang I by angiotensin converting enzyme (ACE). Recent studies have revealed that ACE2, a homologue of ACE, can reduce Ang II production by converting Ang I into Ang 1-9 and converting Ang II into Ang 1-7. In addition to the heart, kidneys, vascular endothelial cells and smooth muscle cells, ACE2 also expresses in skeletal muscles. Our preliminary data showed that ACE2 protein level was significantly reduced in skeletal muscles in ageing mice, whereas transcutaneous electrical nerve stimulation (TENS) of sciatic nerve increased ACE2 expression in skeletal muscles. We hypothesize that stimulation of skeletal muscles increases ACE2 expression in skeletal muscles and reduce plasma Ang II level and increase Ang 1-7 in aged mice. To test this hypothesis, this study will first test whether TENS- increase muscle ACE2 expression is stimulation and contraction dependent in aged mice; Then we will determine whether TENS-enhanced ACE2 expression causes increased plasma Ang 1-7 and decreasd Ang II in aged mice. The results of this study will build a foundation for our future study to explore and develop novel anti-ageing approaches by enhancing endogenous anti-Ang II mechanisms, such as inducing ACE2 expression in skeletal muscles, with non-invasive, non- chemical means, such as TENS.

血管紧张素II （angii）在衰老和衰老相关疾病中起着有害作用。