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 $(PGI_{2})$ 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 $(PGI_{2})$ 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 $(PGI_{2})$ generation. In conclusion, vascular LDs formation and ATGL-dependent $(PGI_{2})$ generation represent a universal response to vascular pro-inflammatory insult.
Wydział Lekarski : Zakład Farmakologii, Pion Prorektora ds. badań naukowych : Jagiellońskie Centrum Rozwoju Leków, Szkoła Doktorska Nauk Ścisłych i Przyrodniczych