巨细胞血氧酶-1调节过氧酸盐介导的血管损伤,并加剧腹腔大动脉动脉瘤的发展
Liangliang Jia1,2,3, Yufei Wang1,2,3, Chunna Jin1,2,3
1Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
American journal of physiology. Cell physiology
|April 22, 2025
概括
巨细胞衍生的血氧酶-1 (HO-1) 通过增加可诱导氧化合成酶 (iNOS) 依赖的过氧和光滑肌肉细胞 (SMC) 亡,驱动腹腔大动脉动脉瘤 (AAA). 在巨细胞中抑制HO-1为AAA提供了潜在的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 血管生物学 血管生物学
背景情况:
- 巨细胞介导的炎症在腹腔大动脉动脉瘤 (AAA) 发病过程中至关重要.
- 巨细胞中的血氧酶-1 (HO-1) 在AAA中加剧炎症和氧化损伤.
- 了解巨HO-1的作用对于AAA治疗的发展至关重要.
研究的目的:
- 在AAA发育中研究巨细胞衍生HO-1的功能.
- 阐明将巨细胞HO-1与AAA进展联系起来的分子机制.
- 确定AAA的潜在治疗点.
主要方法:
- 使用实验性酸诱导的AAA模型.
- 雇佣了有条件的小鼠,缺乏HO-1.
- 研究了可诱导的氧化合成酶 (iNOS) 表达和过氧化生成.
- 在体外共培养系统中与骨髓衍生的巨细胞和光滑肌肉细胞 (SMC) 进行.
主要成果:
- 在AAA组织内的巨细胞中,HO-1表达显著增加.
- 骨髓细胞中的HO-1缺乏减少了AAA光扩大和SMC亡.
- 抑制HO-1降低了iNOS蛋白,但并没有降低巨细胞中的mRNA水平.
- 在巨细胞中抑制iNOS通过减少的氧化减弱了SMC亡.
结论:
- 巨细胞衍生的HO-1促进了AAA的发展.
- HO-1通过增加依赖iNOS的过氧酸盐产量来增强AAA的进展.
- HO-1有助于SMC的亡,加剧了AAA.
- 向巨细胞HO-1为AAA提供了一个有前途的治疗途径.
更多相关视频
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
01:28Nitric Oxide Signaling Pathway
4.9K
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...
4.9K
01:24Peroxisomes
8.3K
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
8.3K