Vascular Lipid Droplets Formed in Response to TNF, Hypoxia, or OA: Biochemical Composition and Prostacyclin Generation

Overview

Journal J Lipid Res

Publisher Elsevier

Specialty Biochemistry

Date 2023 Mar 19

PMID 36934842

Authors

Marta Z Pacia

Natalia Chorazy

Magdalena Sternak

Kamila Wojnar-Lason

Stefan Chlopicki

Affiliations

Soon will be listed here.

Abstract

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) 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 PGI 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 PGI generation. In conclusion, vascular LDs formation and ATGL-dependent PGI generation represent a universal response to vascular proinflammatory insult.

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References

Weller P . LEUKOCYTE LIPID BODIES - STRUCTURE AND FUNCTION AS "EICOSASOMES". Trans Am Clin Climatol Assoc. 2017; 127:328-340. PMC: 5216467. View

Maase M, Rygula A, Pacia M, Proniewski B, Mateuszuk L, Sternak M . Combined Raman- and AFM-based detection of biochemical and nanomechanical features of endothelial dysfunction in aorta isolated from ApoE/LDLR-/- mice. Nanomedicine. 2018; 16:97-105. DOI: 10.1016/j.nano.2018.11.014. View

Pacia M, Chorazy N, Sternak M, Fels B, Pacia M, Kepczynski M . Rac1 regulates lipid droplets formation, nanomechanical, and nanostructural changes induced by TNF in vascular endothelium in the isolated murine aorta. Cell Mol Life Sci. 2022; 79(6):317. PMC: 9142475. DOI: 10.1007/s00018-022-04362-7. View

Schrammel A, Mussbacher M, Wolkart G, Stessel H, Pail K, Winkler S . Endothelial dysfunction in adipose triglyceride lipase deficiency. Biochim Biophys Acta. 2014; 1841(6):906-17. PMC: 4000266. DOI: 10.1016/j.bbalip.2014.03.005. View

Pacia M, Czamara K, Zebala M, Kus E, Chlopicki S, Kaczor A . Rapid diagnostics of liver steatosis by Raman spectroscopy via fiber optic probe: a pilot study. Analyst. 2018; 143(19):4723-4731. DOI: 10.1039/c8an00289d. View

Majka Z, Czamara K, Janus J, Kepczynski M, Kaczor A . Prominent hypertrophy of perivascular adipocytes due to short-term high fat diet. Biochim Biophys Acta Mol Basis Dis. 2021; 1868(2):166315. DOI: 10.1016/j.bbadis.2021.166315. View

Wu K, Thiagarajan P . Role of endothelium in thrombosis and hemostasis. Annu Rev Med. 1996; 47:315-31. DOI: 10.1146/annurev.med.47.1.315. View

Czamara K, Stojak M, Pacia M, Zieba A, Baranska M, Chlopicki S . Lipid Droplets Formation Represents an Integral Component of Endothelial Inflammation Induced by LPS. Cells. 2021; 10(6). PMC: 8227392. DOI: 10.3390/cells10061403. View

Czamara K, Adamczyk A, Stojak M, Radwan B, Baranska M . Astaxanthin as a new Raman probe for biosensing of specific subcellular lipidic structures: can we detect lipids in cells under resonance conditions?. Cell Mol Life Sci. 2020; 78(7):3477-3484. PMC: 8038953. DOI: 10.1007/s00018-020-03718-1. View

10.

Kellici T, Tzakos A, Mavromoustakos T . Rational drug design and synthesis of molecules targeting the angiotensin II type 1 and type 2 receptors. Molecules. 2015; 20(3):3868-97. PMC: 6272512. DOI: 10.3390/molecules20033868. View

11.

Triggiani M, Oriente A, Marone G . Differential roles for triglyceride and phospholipid pools of arachidonic acid in human lung macrophages. J Immunol. 1994; 152(3):1394-403. View

12.

Pilarczyk M, Mateuszuk L, Rygula A, Kepczynski M, Chlopicki S, Baranska M . Endothelium in spots--high-content imaging of lipid rafts clusters in db/db mice. PLoS One. 2014; 9(8):e106065. PMC: 4148353. DOI: 10.1371/journal.pone.0106065. View

13.

Frey E, Miller D, Jahr T, Sundan A, Bazil V, Espevik T . Soluble CD14 participates in the response of cells to lipopolysaccharide. J Exp Med. 1992; 176(6):1665-71. PMC: 2119444. DOI: 10.1084/jem.176.6.1665. View

14.

Inoue T, Kobayashi K, Inoguchi T, Sonoda N, Fujii M, Maeda Y . Reduced expression of adipose triglyceride lipase enhances tumor necrosis factor alpha-induced intercellular adhesion molecule-1 expression in human aortic endothelial cells via protein kinase C-dependent activation of nuclear factor-kappaB. J Biol Chem. 2011; 286(37):32045-53. PMC: 3173212. DOI: 10.1074/jbc.M111.285650. View

15.

Kuo A, Lee M, Sessa W . Lipid Droplet Biogenesis and Function in the Endothelium. Circ Res. 2017; 120(8):1289-1297. PMC: 5392152. DOI: 10.1161/CIRCRESAHA.116.310498. View

16.

Gryglewski R . Prostacyclin among prostanoids. Pharmacol Rep. 2008; 60(1):3-11. View

17.

Paternotte E, Gaucher C, Labrude P, Stoltz J, Menu P . Review: behaviour of endothelial cells faced with hypoxia. Biomed Mater Eng. 2008; 18(4-5):295-9. View

18.

Pacia M, Mateuszuk L, Chlopicki S, Baranska M, Kaczor A . Biochemical changes of the endothelium in the murine model of NO-deficient hypertension. Analyst. 2014; 140(7):2178-84. DOI: 10.1039/c4an01870b. View

19.

Arrese E, Saudale F, Soulages J . Lipid Droplets as Signaling Platforms Linking Metabolic and Cellular Functions. Lipid Insights. 2014; 7:7-16. PMC: 4161058. DOI: 10.4137/LPI.S11128. View

20.

Pober J, Sessa W . Evolving functions of endothelial cells in inflammation. Nat Rev Immunol. 2007; 7(10):803-15. DOI: 10.1038/nri2171. View