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Article

Adiposomes from Obese-Diabetic Individuals Promote Endothelial Dysfunction and Loss of Surface Caveolae

by
Imaduddin Mirza
1,
Mohamed Haloul
1,
Chandra Hassan
2,
Mario Masrur
2,
Amro Mostafa
3,
Francesco M. Bianco
2,
Mohamed M. Ali
4,
Richard D. Minshall
2 and
Abeer M. Mahmoud
1,5,*
1
Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
2
Department of Surgery, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
3
Departments of Anesthesiology and Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
4
School of Business and Non-Profit Management, North Park University, Chicago, IL 60625, USA
5
Department of Kinesiology and Nutrition, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA
*
Author to whom correspondence should be addressed.
Cells 2023, 12(20), 2453; https://doi.org/10.3390/cells12202453
Submission received: 22 September 2023 / Revised: 8 October 2023 / Accepted: 10 October 2023 / Published: 15 October 2023
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Abstract

Glycosphingolipids (GSLs) are products of lipid glycosylation that have been implicated in the development of cardiovascular diseases. In diabetes, the adipocyte microenvironment is characterized by hyperglycemia and inflammation, resulting in high levels of GSLs. Therefore, we sought to assess the GSL content in extracellular vesicles derived from the adipose tissues (adiposomes) of obese-diabetic (OB-T2D) subjects and their impact on endothelial cell function. To this end, endothelial cells were exposed to adiposomes isolated from OB-T2D versus healthy subjects. Cells were assessed for caveolar integrity and related signaling, such as Src-kinase and caveolin-1 (cav-1) phosphorylation, and functional pathways, such as endothelial nitric oxide synthase (eNOS) activity. Compared with adiposomes from healthy subjects, OB-T2D adiposomes had higher levels of GSLs, especially LacCer and GM3; they promoted cav-1 phosphorylation coupled to an obvious loss of endothelial surface caveolae and induced eNOS-uncoupling, peroxynitrite generation, and cav-1 nitrosylation. These effects were abolished by Src kinase inhibition and were not observed in GSL-depleted adiposomes. At the functional levels, OB-T2D adiposomes reduced nitric oxide production, shear response, and albumin intake in endothelial cells and impaired flow-induced dilation in healthy arterioles. In conclusion, OB-T2D adiposomes carried a detrimental GSL cargo that disturbed endothelial caveolae and the associated signaling.
Keywords: extracellular vesicles; adiposomes; glycosphingolipids (GSLs); endothelial dysfunction; caveolae; Src kinase; caveolin-1 (cav-1); endothelial nitric oxide synthase (eNOS); shear stress; flow-induced dilation (FID) extracellular vesicles; adiposomes; glycosphingolipids (GSLs); endothelial dysfunction; caveolae; Src kinase; caveolin-1 (cav-1); endothelial nitric oxide synthase (eNOS); shear stress; flow-induced dilation (FID)
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MDPI and ACS Style

Mirza, I.; Haloul, M.; Hassan, C.; Masrur, M.; Mostafa, A.; Bianco, F.M.; Ali, M.M.; Minshall, R.D.; Mahmoud, A.M. Adiposomes from Obese-Diabetic Individuals Promote Endothelial Dysfunction and Loss of Surface Caveolae. Cells 2023, 12, 2453. https://doi.org/10.3390/cells12202453

AMA Style

Mirza I, Haloul M, Hassan C, Masrur M, Mostafa A, Bianco FM, Ali MM, Minshall RD, Mahmoud AM. Adiposomes from Obese-Diabetic Individuals Promote Endothelial Dysfunction and Loss of Surface Caveolae. Cells. 2023; 12(20):2453. https://doi.org/10.3390/cells12202453

Chicago/Turabian Style

Mirza, Imaduddin, Mohamed Haloul, Chandra Hassan, Mario Masrur, Amro Mostafa, Francesco M. Bianco, Mohamed M. Ali, Richard D. Minshall, and Abeer M. Mahmoud. 2023. "Adiposomes from Obese-Diabetic Individuals Promote Endothelial Dysfunction and Loss of Surface Caveolae" Cells 12, no. 20: 2453. https://doi.org/10.3390/cells12202453

APA Style

Mirza, I., Haloul, M., Hassan, C., Masrur, M., Mostafa, A., Bianco, F. M., Ali, M. M., Minshall, R. D., & Mahmoud, A. M. (2023). Adiposomes from Obese-Diabetic Individuals Promote Endothelial Dysfunction and Loss of Surface Caveolae. Cells, 12(20), 2453. https://doi.org/10.3390/cells12202453

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