瓦索斯塔丁-2通过ACE2/MasR/PPARγ/NR1D1/Gas1轴减轻受伤引起的新极端增生症
Qiujing Chen1,2, Jingmeng Liu1,2, Rosalinda Madonna3
1Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Cardiovascular research
|November 13, 2025
概括
血清中较低的血管静止素-2水平与血管塑性手术后的冠状动脉静止相关. 这种,静脉-2,通过ACE2 / NR1D1 / Gas1通路抑制血管光滑肌肉细胞增殖和新极度增生.
科学领域:
- 心血管生物学 心血管生物学
- 血管医学 血管医学
- 疾病的分子机制.
背景情况:
- 瓦索斯塔丁-2是一种染色素A衍生的,表现出心血管保护和抗炎作用.
- 血管静止素-2在受伤诱导的血管改造中的作用,特别是皮肤穿刺冠状动脉干预 (PCI) 后的复原,尚不清楚.
研究的目的:
- 在接受PCI的患者中,研究血清中血管静止素-2水平与静止症之间的关联.
- 在小鼠模型中探索静静素-2在减轻血管新极度增生症方面的治疗潜力.
主要方法:
- 在PCI后的884名患者 (442名患者和442名患者没有复原症) 中测量了血清血管静止素-2水平.
- 用大腿动脉损伤的小鼠模型来评估复合静止素-2的效果.
- 采用多种omics方法,包括RNA测序和质谱,以阐明分子途径.
主要成果:
- 与对照组相比,患有复原症的患者表现出与控制组相比血清中血管静止素-2水平显著降低 (P < 0.001).
- 在小鼠中,静止素-2的使用显著降低了neointimal增生症和抑制了血管光滑肌细胞 (VSMC) 现型切换.
- 机理学研究显示,静脉定-2与血管素转化酶2 (ACE2) 结合,激活NR1D1-Gas1通路,促进VSMC亡并抑制增殖.
结论:
- 血清中血管静止素-2水平降低是血管整形术后冠状动脉静止症相关的生物标志物.
- 瓦索斯塔丁-2通过减弱新极端生长和通过ACE2/NR1D1/Gas1信号轴抑制VSMC增殖,显示出治疗潜力.
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
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
2.3K
Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
2.3K
Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
1.1K
Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
1.1K
Antihypertensive Drugs: Angiotensin II Receptor Blockers
2.4K
In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
2.4K
Mechanism of Angiogenesis
6.6K
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...
6.6K
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
447
Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
447


