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

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 标记物导致 ROS、ER 应激、自噬缺陷、内皮功能障碍增加，随后， 血管重塑受损。然而，CSE/H2S 信号传导的调节机制和作用 衰老过程中的血管重塑和相关功能尚不清楚。目前的提案将揭示新颖的 通过研究 CSE/H2S 对内皮功能和老化血管系统的调节信息 假设衰老过程中内皮细胞 CSE 缺乏，随后 H2S/NO 生物利用度降低 损害血管重塑。该假设将通过两个具体目标进行检验： 1. 确定分子 2. 确定减少衰老过程中 CSE/H2S 缺乏的机制以及减少内皮细胞 CSE/H2S 的影响 与年龄相关的血管功能障碍。该提案的目标是至少生成初步数据 两份高影响力的同行评审手稿，并在 2024 年底之前提交我的 R01。

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.