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Mitochondrial dysfunction drives persistent vascular fibrosis in rats after short-term exposure of PM2.5
Ruihong Ning1, Yanfeng Shi1, Jinjin Jiang1
1Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China.
Abstract:
Nowadays, the great majority of toxicological studies have focused on immediate cardiovascular effects of simultaneous exposure to long-term or short-term PM2.5; yet, whether the persistent vascular fibrosis will be induced after short-term PM2.5 exposure and its related underlying mechanisms remain unclear. In this study, we adopted SD rats treated with PM2.5 for 1 month and followed by 12 months and 18 months recovery. Results from Doppler ultrasonography and histopathological analysis found that PM2.5-evoked vascular fibrosis was comprised of structural injury, including thickening of aortic media and carotid intima media thickness (CIMT), narrow left common carotid artery (LCCA), collagen deposition, impaired elasticity and functional alterations in aortal stiffness during long-term recovery. The protein expression levels of collagen I, collagen III, proliferating cell nuclear antigen (PNCA), TGF-β and osteopontin (OPN) remained elevated trends in PM2.5-treated groups for the related period than in control groups. Additionally, PM2.5 upregulated the protein expression levels of superoxide dismutase 2 (SOD2), mitochondrial fission related proteins (Drp1 and Fis1), while downregulated the protein expression levels of mitochondrial fusion related proteins (Mfn2 and OPA1). Moreover, PM2.5 significantly activated the mitophagy-related protein expression, including LC3, p62, PINK, Parkin. In summary, our results demonstrated that short-term PM2.5 exposure could trigger mitophagy, further lead to mitochondrial dysfunction which regulated persistent vascular fibrosis during long-term recovery.
Insights
Short-term exposure to fine particulate matter (PM2.5) can cause lasting vascular fibrosis. This occurs through triggering mitophagy and mitochondrial dysfunction, leading to persistent cardiovascular damage.
Area of Science:
- Toxicology
- Cardiovascular Research
- Environmental Health
Background:
- Most studies focus on immediate cardiovascular effects of PM2.5.
- The long-term impact of short-term PM2.5 exposure on vascular fibrosis is unclear.
- Understanding PM2.5's persistent effects is crucial for public health.
Purpose of the Study:
- To investigate if short-term PM2.5 exposure induces persistent vascular fibrosis.
- To elucidate the underlying mechanisms of PM2.5-induced vascular fibrosis.
- To assess long-term cardiovascular structural and functional changes post-exposure.
Main Methods:
- SD rats were exposed to PM2.5 for one month, followed by 12- and 18-month recovery periods.
- Doppler ultrasonography and histopathological analyses were used to evaluate vascular changes.
- Protein expression levels of fibrosis markers, mitochondrial proteins, and mitophagy markers were measured.
Main Results:
- PM2.5 exposure led to aortic media thickening, increased carotid intima-media thickness (CIMT), and reduced artery diameter.
- Elevated collagen deposition, impaired elasticity, and aortic stiffness were observed.
- PM2.5 upregulated fibrosis markers (Collagen I, III, PNCA, TGF-β, OPN), mitochondrial fission proteins (Drp1, Fis1), and mitophagy markers (LC3, p62, PINK, Parkin).
- Mitochondrial fusion proteins (Mfn2, OPA1) were downregulated, indicating mitochondrial dysfunction.
Conclusions:
- Short-term PM2.5 exposure can induce persistent vascular fibrosis during long-term recovery.
- The mechanism involves PM2.5 triggering mitophagy, leading to mitochondrial dysfunction.
- These findings highlight the chronic cardiovascular risks associated with air pollution.
