Vascular lipid droplets formed in response to TNF, hypoxia or OA: biochemical composition and prostacyclin generation. 在对TNF、缺氧或OA的反应中形成的血管脂质滴: 生化成分和前列环素的生成。
Vascular lipid droplets formed in response to TNF, hypoxia or OA: biochemical composition and prostacyclin generation.
发表日期:2023 Mar 17
作者:
Marta Z Pacia, Natalia Chorazy, Magdalena Sternak, Kamila Wojnar-Lason, Stefan Chlopicki
来源:
JOURNAL OF LIPID RESEARCH
摘要:
各种细胞中的脂滴(LDs)的生物起源在各种生理和病理过程中扮演着重要角色。然而,LDs在内皮生理学和病理学中的功能尚不明确。在本研究中,我们研究了经过炎症因子:肿瘤坏死因子(TNF),脂多糖(LPS),血管紧张素II(AngII),缺氧条件或油酸(OA)刺激后,分离的小鼠主动脉血管组织中LDs和前列环素(PGI2)生成的形成。依据拉曼光谱和荧光成像,我们表征了LDs的丰度,大小和生化组成。我们发现,通过脂解的抑制剂:脂肪三酸甘油酯酶(ATGL)阻断,延迟LDs降解,并且同时削弱了所有测试的炎症刺激处理的主动脉中PGI2的产生。此外,通过比较存在或不存在ATGL抑制剂(atglistatin)下缺氧或OA过载条件下内皮LDs的拉曼特征,我们展示了atglistatin不会影响LDs的生物化学组成。总之,无论LDs是否由炎症刺激、缺氧或油酸引起,以及无论它们是由高度不饱和或不那么不饱和的脂质组成,我们观察到LDs的形成均与ATGL相关的PGI2的生成密切相关。最后,血管LDs形成和ATGL-dependentPGI2的生成代表血管炎症损伤的普遍反应。Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Biogenesis of lipid droplets (LDs) in various cells plays an important role in various physiological and pathological processes. However, the function of LDs in endothelial physiology and pathology is not well understood. In the present work, we investigated the formation of LDs and prostacyclin (PGI2) generation in the vascular tissue of isolated murine aortas following activation by pro-inflammatory factors: tumor necrosis factor (TNF), lipopolysaccharides (LPS), angiotensin II (AngII), hypoxic conditions, or oleic acid (OA). The abundance, size, and biochemical composition of LDs was characterized based on Raman spectroscopy and fluorescence imaging. We found that blockade of lipolysis by the adipose triglyceride lipase (ATGL) delayed LDs degradation and simultaneously blunted PGI2 generation in aorta treated with all tested pro-inflammatory stimuli. Furthermore, the analysis of Raman spectra of LDs in the isolated vessels stimulated by TNF, LPS, AngII, or hypoxia uncovered that these LDs were all rich in highly unsaturated lipids and had a negligible content of phospholipids and cholesterols. Additionally, by comparing the Raman signature of endothelial LDs under hypoxic or OA-overload conditions in the presence or absence of ATGL inhibitor, atglistatin, we show that atglistatin does not affect the biochemical composition of LDs. Altogether, independent of whether LDs were induced by pro-inflammatory stimuli, hypoxia, or oleic acid, and of whether they were composed of highly unsaturated or less unsaturated lipids, we observed LDs formation invariably associated with ATGL-dependent PGI2 generation. In conclusion, vascular LDs formation and ATGL-dependent PGI2 generation represent a universal response to vascular pro-inflammatory insult.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.