Stromal Vascular Fraction Restores Vasodilatory Function by Reducing Oxidative Stress in Aging-Induced Coronary Microvascular Disease.
Antioxid Redox Signal
; 38(4-6): 261-281, 2023 02.
Article
en En
| MEDLINE
| ID: mdl-35950616
ABSTRACT
Aims:
The objective of this study is to identify mechanisms for adipose stromal vascular fraction's (SVF) restorative effects on vasodilation in aging-induced coronary microvascular disease (CMD). We hypothesize that reactive oxygen species (ROS) diminish ß1-adrenergic receptor (ß1ADR)- and flow-mediated dilation (FMD) in coronary arterioles, reversible by SVF and adipose-derived stem cells (ADSCs).Results:
SVF attenuates aging-induced chronic accumulation of ROS and pro-oxidant gene and protein expression with enhancement of antioxidant gene and protein expression and glutathione, but not nitric oxide. ADSCs attenuate hydrogen peroxide while restoring nitric oxide and glutathione. Mass spectrometry of SVF- and ADSC-conditioned media reveals abundant antioxidant proteins suggesting a paracrine mechanism. FMD and ß1ADR-mediated dilation diminished with aging, restored with SVF and ADSCs. FMD was restored by a switch in the acute signaling mediator from hydrogen peroxide in aging to peroxynitrite with SVF and ADSCs. Vasorelaxation to ß1ADR-agonism was mechanistically linked with hydrogen peroxide, nitric oxide, and glutathione. Exogenous ROS eliminates isoproterenol-mediated dilation in youth that is blocked by inhibition of pro-desensitization and internalization proteins while nitric oxide enhances isoproterenol-mediated dilation in aging. Innovation We introduce a novel mechanism by which ROS impacts ß1ADR trafficking the ROS/RNS-ß1ADR desensitization and internalization axis. Aging-induced ROS shunts ß1ADR from the plasma membrane into endosomes. SVF reduces oxidative burden, restoring functional ß1ADR.Conclusions:
SVF (and ADSCs to a lesser extent) reduce oxidative stress, and restore flow- and ß1ADR-mediated vasodilation in aging. SVF represents a promising therapeutic strategy for CMD by addressing root cause of pathology; that is, oxidative stress-mediated hyperconstriction. Antioxid. Redox Signal. 38, 261-281.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Vasodilatación
/
Fracción Vascular Estromal
Idioma:
En
Revista:
Antioxid Redox Signal
Asunto de la revista:
METABOLISMO
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos