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。年龄相关的分子信号转导改变 标记物导致ROS增加，内质网应激，自噬缺陷，内皮功能障碍，随后， 血管重塑受损。然而，CSE/H_2S信号转导的调控机制和作用 血管重塑和相关功能在衰老中的作用尚不清楚。目前的提案将揭示出新的 通过研究CSE/H_2S对内皮功能和衰老血管系统的调节作用 假设内皮细胞CSE在衰老过程中缺乏，并随后降低了H2S/NO的生物利用度 损害血管重塑。这一假设将通过两个具体的目标来检验：1.确定分子 衰老中CSE/H_2S缺陷减少的机制以及2.确定减少内皮细胞CSE/H_2S对 年龄相关性血管功能障碍。这项提案的目标是产生初步数据，至少 两份高影响力的同行评审稿，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.