TRIM65通过与VCAM-1相互作用抑制oxLDL诱导的内皮炎症在动脉生成中的VCAM-1
Xiao-Feng Ma1, Yi-Ren Zhou1, Zhi-Xiang Zhou2
1Department of Cardiology, Affiliated Nanhua Hospital, University of South China, Hengyang City, Hunan Province 421001, PR China.
Current medicinal chemistry
|August 23, 2023
概括
三方基因65 (TRIM65) 蛋白通过向血管细胞粘附分子1 (VCAM-1) 来降解,减少动脉样硬化中的炎症. 这一发现表明TRIM65是治疗AS的内皮炎症的潜在治疗标.
科学领域:
- 心血管生物学 心血管生物学
- 分子炎症分子炎症
- 动脉样硬化研究 动脉样硬化研究
背景情况:
- 内皮细胞激活,标志着血管细胞粘附分子1 (VCAM-1) 的增加,是动脉样硬化 (AS) 发展的关键.
- 抑制VCAM-1介导的炎症对于AS的预防和治疗至关重要.
- 三方基因 (TRIM) 蛋白TRIM65与炎症调节有关.
研究的目的:
- 为了研究TRIM65在内皮炎症中的作用.
- 为了探索TRIM65与VCAM-1在动脉生成中的相互作用.
主要方法:
- 在体外研究中,使用人静脉内皮细胞 (HUVEC) 用氧化低密度脂蛋白 (oxLDL) 治疗.
- 在体内使用ApoE-/-小鼠和TRIM65淘汰模式的研究.
- 西方斑点和免疫光染色以评估蛋白质表达.
- 涉及到无处不在测试的机制研究.
主要成果:
- 在HUVEC中,TRIM65过度表达减少了oxLDL诱导的VCAM-1表达,单细胞粘附和炎症性细胞因子释放.
- TRIM65的倒置加剧了VCAM-1的表达和炎症反应.
- 在小鼠大动脉斑块中,TRIM65表达高;在TRIM65淘汰小鼠中,VCAM-1水平升高.
- TRIM65与VCAM-1直接相互作用,将其定位为K48链接的无处不在.
结论:
- TRIM65通过向VCAM-1进行无处不在的作用来减轻内皮炎症.
- 在AS中,TRIM65代表了抑制内皮炎症的潜在治疗标.
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
Nitric Oxide Signaling Pathway
5.1K
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...
5.1K
Mechanism of Angiogenesis
5.6K
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...
5.6K
Inflammatory Response I: Vascular and Cellular
11.3K
The inflammatory response is the body's defense against infection, injury, or irritation from bacteria, trauma, toxins, or heat. Inflammation helps locate and destroy pathogens and remove damaged tissue elements to heal the body. During this initial phase, fluid, blood products, and nutrients migrate to the injured area, resulting in redness, heat, swelling, ache, and loss of function. Moreover, signs of systemic inflammation include fever, increased WBC count, malaise, anorexia, nausea,...
11.3K
Cholesterol: Significance and Regulation
582
Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
Considering cholesterol and...
582
TGF - β Signaling Pathway
7.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K


