Vascular lipid droplets formed in response to TNF, hypoxia, or OA: biochemical composition and prostacyclin generation

by Selleckchem | Jun 05 2023

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 proinflammatory factors: tumor necrosis factor (TNF), lipopolysaccharides (LPS), angiotensin II (AngII), hypoxic conditions, or oleic acid (OA). The abundance, size, and biochemical composition of LDs were 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 proinflammatory 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 (Atgl), we show that Atgl does not affect the biochemical composition of LDs. Altogether, independent of whether LDs were induced by pro-inflammatory stimuli, hypoxia, or OA 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 proinflammatory insult.

Comments：

The present work investigates the formation and function of lipid droplets (LDs) in endothelial cells in response to proinflammatory stimuli, including TNF, LPS, AngII, hypoxia, and OA. The study characterizes the abundance, size, and biochemical composition of LDs using Raman spectroscopy and fluorescence imaging. The authors demonstrate that blockade of lipolysis by ATGL delays LDs degradation and blunts PGI2 generation in aorta treated with all tested proinflammatory stimuli. The Raman spectra analysis reveals that LDs induced by TNF, LPS, AngII, or hypoxia are all rich in highly unsaturated lipids and have a negligible content of phospholipids and cholesterols. Additionally, the study shows that ATGL does not affect the biochemical composition of LDs induced by hypoxia or OA-overload. Therefore, the authors conclude that regardless of the proinflammatory stimulus and the biochemical composition of LDs, ATGL-dependent PGI2 generation represents a universal response to vascular proinflammatory insult. These findings suggest that LDs formation and ATGL-mediated PGI2 generation may play a critical role in endothelial physiology and pathology, particularly in response to vascular proinflammatory stimuli.