剪切压力诱导的内皮HEG1信号调节血管度和血压
Wenrun Wu1, Jun Liu2, Xiaoli Chen1
1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center, Shanghai Heart Failure Research Center, Department of Cardiology, Department of Cardiovascular Surgery, Shanghai East Hospital, School of Medicine, Tongji University, 150 Jimo Rd, Pudong New District, Shanghai 200120, China.
European heart journal
|September 23, 2025
概括
内皮心脏发育蛋白与EGF类似域1 (HEG1) 通过控制PHACTR1降解来调节血压. 降低HEG1会损害血管扩张,通过一种新的剪切敏感通路导致高血压.
科学领域:
- 心血管生物学 心血管生物学
- 内皮细胞功能 内皮细胞功能
- 高血压的分子机制 高血压的分子机制
背景情况:
- 内皮细胞 (ECs) 感知血管扩张的剪切应力,对血压 (BP) 调节至关重要.
- 削减剪切应激信号的损害有助于内皮功能障碍和高血压.
- 具有EGF类似域1 (HEG1) 的心脏发育蛋白是一种流动敏感的EC蛋白,与心血管风险降低有关.
研究的目的:
- 研究内皮质HEG1在血压调节中的作用.
- 阐明HEG1影响内皮功能和高血压的分子机制.
主要方法:
- 现象范围的关联研究,计算流体动力学和单细胞RNA测序.
- 用血压和血管功能的分析进行内皮特异性Heg1缺失的小鼠模型.
- 蛋白质组学,转录组学和无处不在分析以确定调节途径.
主要成果:
- 在高血压患者中,血HEG1水平因减小剪切应力而降低.
- 在小鼠体内皮质HEG1缺乏导致血压升高和血管扩张受损.
- HEG1促进PHACTR1的降解,抑制SP1介导的eNOS转录和NO的产生.
结论:
- 在BP调节中确定了一种新的剪切敏感内皮HEG1信号通路.
- HEG1在PHACTR1降解中的作用对于维持内皮功能和正常血压至关重要.
- 这一途径为高血压提供了潜在的治疗点.
更多相关视频
相关概念视频
Regulation of Angiogenesis and Blood Supply
3.3K
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...
3.3K
Autoregulation of Blood Flow
7.5K
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....
7.5K
Neural Regulation of Blood Pressure
6.9K
The neural regulation of blood pressure involves intricate interactions between the autonomic nervous system (ANS) and cardiovascular system, ensuring adequate perfusion of tissues. This regulation primarily occurs through baroreceptor and chemoreceptor reflexes, involving both short-term and long-term mechanisms.
Baroreceptor Reflex
Baroreceptors, located in the carotid sinuses and aortic arch, detect changes in blood pressure. When blood pressure rises, these stretch-sensitive receptors...
Baroreceptor Reflex
Baroreceptors, located in the carotid sinuses and aortic arch, detect changes in blood pressure. When blood pressure rises, these stretch-sensitive receptors...
6.9K
Hormonal Regulation of Blood Pressure
5.9K
Endocrinal or hormonal intervention in the cardiovascular system is predominantly exerted by the catecholamines - epinephrine and norepinephrine, as well as a slew of hormones that interact with renal function to modulate blood volume.
Epinephrine and Norepinephrine
The adrenal medulla releases epinephrine and norepinephrine, catecholamines that enhance and extend the sympathetic or "fight or flight" physiological response. These hormones escalate heart rate and the force of contraction...
Epinephrine and Norepinephrine
The adrenal medulla releases epinephrine and norepinephrine, catecholamines that enhance and extend the sympathetic or "fight or flight" physiological response. These hormones escalate heart rate and the force of contraction...
5.9K
Hypertension II: Pathophysiology
803
Hypertension is a chronic condition in which the blood's force against artery walls is excessively high, posing risks such as heart disease. The condition's underlying mechanisms involve complex interactions among the cardiovascular, kidney, and autonomic nervous systems.Renin-Angiotensin-Aldosterone System (RAAS): This system significantly influences blood pressure regulation. When blood pressure decreases, the kidneys secrete renin. This enzyme transforms angiotensinogen, a plasma protein,...
803
Hypertension and Regulation of Blood Pressure
3.8K
Hypertension, the most common cardiovascular disease, is diagnosed through repeated measurements of elevated blood pressure. Its risks, including damage to the kidney, heart, and brain, are directly proportional to blood pressure levels. Starting from 115/75 mm Hg, the risk of cardiovascular disease doubles with each increment of 20/10 mm Hg. The diagnosis relies on blood pressure measurements, not on patient symptoms, as hypertension is often asymptomatic until end-organ damage is imminent or...
3.8K


