SIRT1-mediated vasodilatation: from inside to outside
Grant Data
Project Title
SIRT1-mediated vasodilatation: from inside to outside
Principal Investigator
Professor Wang, Yu
(Principal Investigator (PI))
Duration
48
Start Date
2022-01-01
Amount
1499800
Conference Title
SIRT1-mediated vasodilatation: from inside to outside
Keywords
Endothelium, Mitochondria, PVAT, sGC, SIRT1, Vasodilatation
Discipline
Others - Medicine, Dentistry and Health
HKU Project Code
08192306
Grant Type
Health and Medical Research Fund - Full Grant
Funding Year
2020
Status
On-going
Objectives
Objectives-Abnormal vasodilatory response represents an early event during vascular ageing. Endothelium and perivascular adipose tissue (PVAT) both play important roles in regulating vascular tone. SIRT1 is a longevity regulator possessing potent anti-vascular ageing activity. The present proposal aims to investigate the molecular mechanisms underlying the vasodilatory response mediated by SIRT1 in PVAT and the potential clinical applications. Hypotheses-SIRT1 in endothelium and PVAT act to promote vasodilatation through different but complement mechanisms. Such synergistic effects prevent hypertension and ischemic heart diseases associated with ageing and/or obesity. Subjects-Mice with endothelium- or adipose tissue-specific overexpression of human SIRT1 and their wild type littermates will be used for evaluating arterial tone responses, cardiac structure and function under various pathophysiological conditions. Interventions-All mice will be subjected to standard chow or high fat diet feeding. Thoracic and abdominal aorta as well as mesenteric arteries will be collected at different ages, before and after treatment, for analyzing the vascular tone reactivity using the wire myography. Blood pressure will be monitored in mice implanted with the wireless HD‐X11 telemetry device. Ischemic cardiac injury will be induced by temporary or permanent coronary artery occlusion. Main outcomes-The results will uncover the tissue-specific anti-vascular ageing activity of SIRT1, elucidate the signaling mechanisms underlying SIRT1 in PVAT-mediated vasodilatation, and provide important information on the potential clinical applications of SIRT1-targeted therapy in the prevention and treatment of cardiovascular diseases.