血液流动模式通过差异性S-化和S-氧化来切换VEGFR2活性
Dong Hoon Kang1, Yerin Kim1, Seongchun Min1
1Department of Life Science, Ewha Womans University, Seoul 03760, Republic of Korea.
Cell reports
|November 1, 2023
概括
血流通过囊蛋白修饰来调节血管内皮生长因子受体-2 (VEGFR2) 活性. 这种氧化还原调节对于保持动脉内皮完整性和防止损伤至关重要.
科学领域:
- 心血管生物学 心血管生物学
- 内皮细胞生理学 内皮细胞生理学
- 电解氧信号传输 电解氧信号传输
背景情况:
- 血管内皮生长因子受体-2 (VEGFR2) 对于血管平衡至关重要.
- 它的激活和非激活对内皮细胞功能至关重要.
- 血流在调节VEGFR2活性中的作用仍然不清楚.
研究的目的:
- 研究血液流动模式如何影响VEGFR2的激活和失活.
- 阐明VEGFR2.2的流量依赖性氧化还原调节机制.
- 确定动脉内皮中VEGFR2氧化还原变化的体内重要性.
主要方法:
- 研究了VEGFR2的氨酸修饰 (氧化和S-化),以应对不同的流量条件 (平面与振荡).
- 研究了NADPH氧化酶-4和内皮氧化合成酶 (eNOS) 在流动诱导的VEGFR2修饰中的作用.
- 使用小鼠动脉部分绑定模型与野生类型和C1206S突变VEGFR2小鼠评估体内后果.
主要成果:
- 振荡流通过NADPH氧化酶-4在Cys1206诱导VEGFR2氧化,从而导致失活.
- 层状流促进了eNOS表达和VEGFR2在Cys1206的S-化,抵消了氧化失活.
- 具有耐氧化VEGFR2 (C1206S) 的小鼠受到受血流干扰引起的内皮损伤和内皮增生的保护.
结论:
- 血液流动通过可逆的氨酸氧化和S-化,动态调节VEGFR2活性.
- 流量依赖于VEGFR2的氧化还原控制是维持动脉内皮完整性的关键机制.
- 向VEGFR2氧化还原修饰可能为血管疾病提供治疗策略.
相关概念视频
Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
Mechanism of Angiogenesis
5.5K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
5.5K
Nitric Oxide Signaling Pathway
5.0K
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.0K
Autoregulation of Blood Flow
2.4K
Autoregulation mechanisms are characterized by their inherent capacity for self-regulation without necessitating specific nervous stimulation or endocrine control. These mechanisms facilitate the adjustment of blood flow and, therefore, perfusion specific to each tissue region. This self-regulation encompasses chemical signals and myogenic controls.
Chemical Signaling in Autoregulation
Chemical signaling operates at the precapillary sphincter level, inciting either contraction or relaxation....
Chemical Signaling in Autoregulation
Chemical signaling operates at the precapillary sphincter level, inciting either contraction or relaxation....
2.4K


![Development and Characterization of In Vitro Microvessel Network and Quantitative Measurements of Endothelial [Ca2+]i and Nitric Oxide Production](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F54014.jpg&w=3840&q=50)