通过在内皮细胞中通过脱基化增强VEGFA分泌,SIRT6促进血管生成
Runyang Feng1, Shuangshuang Chen2, Shichao Duan3
1Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Fenglin Road, Shanghai 200032, China.
Journal of molecular and cellular cardiology
|January 3, 2025
概括
赛尔图因6 (SIRT6) 通过从VEGFA中去除myristoyl组来调节血管生成,从而增强其分泌. 这种脱基化活性为缺血性心血管疾病提供了潜在的治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子机制的分子机制
背景情况:
- 血管新生在缺血性心血管疾病中至关重要,涉及表观遗传调节.
- 锡尔图因6 (SIRT6) 以其脱乙酶活性而闻名,但其脱甲酶功能和基质的理解较少.
研究的目的:
- 研究SIRT6脱基酶活性在血管生成中的作用.
- 为了确定参与内皮细胞功能SIRT6的myristoylated基质.
主要方法:
- 内皮细胞特异性SIRT6淘汰小鼠模型.
- 在体外内皮细胞测定 (迁移,管形成).
- 低氧治疗,基化试验 (CLICK IT) 和VEGFA分泌分析.
- 关于SIRT6突变的过度表达研究.
主要成果:
- 在小鼠中,SIRT6敲除减弱了血管生成,并减少了内皮细胞迁移和管形成.
- 在低氧状态下,SIRT6会影响细胞内VEGFA和全球基基化.
- VEGFA被确定为SIRT6的基基质,而SIRT6通过脱化促进了VEGFA的分泌.
- 过度表达SIRT6挽救了因抑制脱基化而导致的内皮功能受损.
结论:
- SIRT6通过demyristoylatingVEGFA来调节血管生成,从而增加其分泌.
- 向SIRT6脱基酶活性为缺血性心血管疾病提供了一个新的治疗策略.
相关概念视频
01:24Regulation of Angiogenesis and Blood Supply
2.5K
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...
2.5K
01:10Mechanism of Angiogenesis
5.2K
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...
5.2K
01:22PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K
03:03mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K