Exercise improves angiogenic function of circulating exosomes in type 2 diabetes: Role of exosomal SOD3.

Autor: Abdelsaid K; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA.; Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia, USA., Sudhahar V; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA.; Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia, USA.; Department of Pharmacology and Toxicology, Medical College of Georgia at Augusta University, Augusta, Georgia, USA., Harris RA; Georgia Prevention Institute, Augusta, Georgia, USA., Das A; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA.; Department of Pharmacology and Toxicology, Medical College of Georgia at Augusta University, Augusta, Georgia, USA., Youn SW; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA.; Department of Physiology and Biophysics, University of Illinois, Chicago, Illinois, USA., Liu Y; Department of Cell Biology, Medical College of Georgia at Augusta University, Augusta, Georgia, USA., McMenamin M; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA., Hou Y; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA., Fulton D; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA.; Department of Pharmacology and Toxicology, Medical College of Georgia at Augusta University, Augusta, Georgia, USA., Hamrick MW; Department of Cell Biology, Medical College of Georgia at Augusta University, Augusta, Georgia, USA., Tang Y; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA.; Department of Medicine (Cardiology), Medical College of Georgia at Augusta University, Augusta, Georgia, USA., Fukai T; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA.; Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia, USA.; Department of Pharmacology and Toxicology, Medical College of Georgia at Augusta University, Augusta, Georgia, USA., Ushio-Fukai M; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA.; Department of Medicine (Cardiology), Medical College of Georgia at Augusta University, Augusta, Georgia, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2022 Mar; Vol. 36 (3), pp. e22177.
DOI: 10.1096/fj.202101323R
Abstrakt: Exosomes, key mediators of cell-cell communication, derived from type 2 diabetes mellitus (T2DM) exhibit detrimental effects. Exercise improves endothelial function in part via the secretion of exosomes into circulation. Extracellular superoxide dismutase (SOD3) is a major secretory copper (Cu) antioxidant enzyme that catalyzes the dismutation of O 2 •- to H 2 O 2 whose activity requires the Cu transporter ATP7A. However, the role of SOD3 in exercise-induced angiogenic effects of circulating plasma exosomes on endothelial cells (ECs) in T2DM remains unknown. Here, we show that both SOD3 and ATP7A proteins were present in plasma exosomes in mice, which was significantly increased after two weeks of volunteer wheel exercise. A single bout of exercise in humans also showed a significant increase in SOD3 and ATP7A protein expression in plasma exosomes. Plasma exosomes from T2DM mice significantly reduced angiogenic responses in human ECs or mouse skin wound healing models, which was associated with a decrease in ATP7A, but not SOD3 expression in exosomes. Exercise training in T2DM mice restored the angiogenic effects of T2DM exosomes in ECs by increasing ATP7A in exosomes, which was not observed in exercised T2DM/SOD3 -/- mice. Furthermore, exosomes overexpressing SOD3 significantly enhanced angiogenesis in ECs by increasing local H 2 O 2  levels in a heparin-binding domain-dependent manner as well as restored defective wound healing and angiogenesis in T2DM or SOD3 -/- mice. In conclusion, exercise improves the angiogenic potential of circulating exosomes in T2DM in a SOD3-dependent manner. Exosomal SOD3 may provide an exercise mimetic therapy that supports neovascularization and wound repair in cardiometabolic disease.
(© 2022 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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