STING1-accelerated vascular smooth muscle cell senescence-associated vascular calcification in diabetes is ameliorated by oleoylethanolamide via improved mitochondrial DNA oxidative damage
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View abstract on PubMed
Summary
This summary is machine-generated.Oleoylethanolamide (OEA) alleviates diabetic vascular calcification by inhibiting STING1-mediated senescence and mitochondrial damage. This finding offers new therapeutic targets for cardiovascular disease prevention in diabetic patients.
Area Of Science
- Cardiovascular Biology
- Cellular Aging
- Metabolic Disease Research
Background
- Vascular calcification is a major risk factor for cardiovascular disease, particularly in elderly and diabetic individuals.
- Senescent vascular smooth muscle cells (VSMCs) contribute to vascular calcification, but the underlying mechanisms are not fully understood.
- Mitochondrial dysfunction and aberrant activation of the stimulator of interferon gene 1 (STING1) pathway are implicated in aging and disease.
Purpose Of The Study
- To investigate the role of STING1 in mitochondrial dysfunction-driven vascular calcification and VSMC senescence in diabetes.
- To evaluate the therapeutic potential of oleoylethanolamide (OEA) in mitigating these pathological processes.
Main Methods
- Utilized in vivo diabetic rat/mouse aorta calcification models and an in vitro VSMC calcification model induced by Nε-carboxymethyl-lysine (CML).
- Assessed senescence, STING1 signaling, mitochondrial damage, and oxidative stress markers.
- Employed STING1-knockout mice and STING1-knockdown VSMCs to confirm STING1's role.
- Investigated the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2) and reactive oxygen species (ROS).
Main Results
- Diabetic conditions significantly increased VSMC senescence, STING1 activation, and mitochondrial damage, leading to vascular calcification.
- OEA treatment markedly reduced calcification, senescence, and mitochondrial damage.
- STING1 knockout/knockdown prevented CML-induced calcification and senescence.
- OEA enhanced cellular antioxidant capacity via Nrf2 activation, counteracting CML-induced mitochondrial DNA damage and subsequent STING1 pathway activation.
Conclusions
- STING1 is a key mediator of mitochondrial dysfunction-induced VSMC senescence and vascular calcification in diabetes.
- OEA demonstrates significant vasoprotective effects by targeting the STING1 pathway and enhancing antioxidant defense through Nrf2.
- Targeting STING1 represents a promising therapeutic strategy for preventing and treating diabetic vascular calcification.
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