Cystathionine Gamma Lyase (CSE) and Hydrogen Sulfide Regulation of Vascular Aging

胱硫醚γ裂解酶 (CSE) 和硫化氢对血管老化的调节

• 批准号: 10715408
• 负责人: Gopi K Kolluru
• 金额: $ 21.9万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10715408
• 关键词: ATR gene; Acceleration; Age; Aging; Alzheimer' s Disease; Aorta; Atherosclerosis; Attenuated; Autophagocytosis; Award; Biological Availability; Biology; Blood Vessels; Cardiovascular Diseases; Cell Separation; Cell physiology; Collaborations; Cystathionine; Cysteine Desulfhydrase; DNA Damage; DNA Repair; Data; Defect; Disease; Endothelial Cells; Endothelium; Female; Free Radicals; Genetic; Goals; Growth; Harvest; Human; Hydrogen Sulfide; Impairment; Inflammatory; Ischemia; Length; Longevity; Lyase; Manuscripts; Measures; Mediating; Mediator; Molecular; Mus; Organelles; Organism; Oxidation-Reduction; Oxidative Stress; Pathology; Peer Review; Phosphotransferases; Process; Protein Kinase; Proteins; Regulation; Research; Role; Signal Transduction; Sirtuins; Stress; Stroke; Sulfides; Telomerase; Telomere Shortening; Therapeutic; Time; Vascular Diseases; Vascular remodeling; Vasodilation; age effect; age related; aged; ataxia telangiectasia mutated protein; cardiovascular risk factor; cofactor; cytokine; endoplasmic reticulum stress; endothelial dysfunction; inhibition of autophagy; macromolecule; male; novel; pharmacologic; polysulfide; response; sulfhydration; therapeutic target

PROJECT ABSTRACT Aging is an independent risk factor for cardiovascular diseases. Altered molecular signaling in age-related markers leads to increased ROS, ER stress, autophagy defects, endothelial dysfunction and subsequently, impaired vascular remodeling. However, the regulatory mechanisms, and the role of CSE/H2S signaling in vascular remodeling and associated functions in aging are unknown. The current proposal will reveal novel information regarding CSE/H2S regulation on endothelial function and aging vasculature by investigating the hypothesis that endothelial-cell CSE deficiency in aging, and subsequently reduced H2S/NO bioavailability impairs vascular remodeling. This hypothesis will be examined by two specific aims that 1. identify the molecular mechanisms of reduced CSE/H2S deficiency in aging and 2. determine reduced endothelial CSE/H2S effects on age-associated vascular dysfunction. The goal of this proposal is to generate preliminary data towards at least two high impact peer-reviewed manuscript and submit my R01 by end of 2024.

项目摘要 衰老是心血管疾病的独立危险因素。与年龄相关的分子信号改变 标志物导致ROS增加、ER应激、自噬缺陷、内皮功能障碍，随后， 血管重塑受损。然而，调节机制和CSE/H2S信号传导在 衰老中的血管重塑和相关功能是未知的。目前的提案将揭示新颖性 通过研究CSE/H2S对内皮功能和血管老化的调节， 假设衰老中内皮细胞CSE缺乏，随后H2S/NO生物利用度降低 损害血管重塑。这一假设将通过两个具体目标进行检验，即1。识别分子 减少CSE/H2S缺乏的衰老机制和2.确定降低的内皮CSE/H2S对 与年龄相关的血管功能障碍本提案的目标是生成初步数据， 两篇高影响力的同行评审手稿，并在2024年底前提交我的R 01。