N-acetyl cysteine ameliorates aortic fibrosis by promoting M2 macrophage polarization in aging mice

Abstract

Background: Vascular fibrosis is a universal phenomenon associated with aging, and oxidative stress plays an important role in the genesis of vascular damage in line with the aging process. However, whether antioxidants can ameliorate vascular fibrosis remains unclear. Objectives: The present study was to determine antioxidant N-acetylcysteine (NAC) could ameliorates aortic fibrosis in aging wild-type C57BL/6 mice. Methods : The aortas were harvested from both 12-week and 60-week wild-type mice. The 60-week mice were treated with and without the NAC for 12 weeks starting at the age of 48 weeks. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining of aortic samples were performed, and the levels of reactive oxygen species (ROS), RNA expression of GAPDH, TNF-α, MCP-1, IL-6, IL-10, IL-4, SIRT-1, SIRT-3, FOXO-1, and macrophage polarization were determined. Results: There is a positive relationship between collagen deposition and the M1/M2 macrophage ratio in the aortic wall of aged wild-type C57BL/6 mice. The higher collagen area percentage in the aortas of 60-week-old mice than in 12-week-old mice was reversed by NAC. NAC could not impact the total number of macrophages, but partly promoted M2 macrophage polarization. By performing qRT-PCR using aortic samples from these mice, we identified that SIRT-1, SIRT-3, FOXO-1 could be somehow responsible for aging-related fibrosis. Conclusions: NAC ameliorates aortic fibrosis in aging wild type mice partly by promoting M2 macrophage polarization.

Epigenetic regulation of aging: implications for interventions of aging and diseases

“… 265 Similarly, NAC attenuates aging-related oxidative damage and neurodegeneration in rat brains by upregulating sirtuin-1 and downregulating several SASP factors (TNF-α, IL-1β, IL-6). 266 In addition, NAC extends the lifespan of mice 267 and ameliorates a series of aging-related diseases in rodents, such as AD, 268 , 269 aortic fibrosis, 270 immunosenescence, 271 oxidative stress and senescence in the lung, 272 bone loss in ovariectomized mice, 273 adipose tissue senescence and metabolic abnormalities, 243 and aging-related hearing loss. 274 …”

Comparison of the efficacy and safety of different doses of atropine for myopic control in children: a meta-analysis

“…The ESs of different doses of atropine groups all showed large treatment effects ( Supplementary Figure S2A ). In exploring the dose‒response relationship between atropine dose and ESs, we observed a significant linear correlation after excluding Zhu’s and Nucci’s studies which provided extreme findings (y = 1.08x + 0.86; r = 0.370, R 2 = 0.137; p = 0.013; Supplementary Figure S3A ) ( Zhu et al, 2021 ; Nucci et al, 2023 ). However, when we further exploring their nonlinear correlation, we found that the logarithmic equation has a better fitting effect (y = 0.23lnx+1.84, R 2 = 0.173, p = 0.005, Figure 3A ).…”

Lipoteichoic acid restrains macrophage senescence via β‐catenin/FOXO1/REDD1 pathway in age‐related osteoporosis

“…It is reported that FOXO1 participates in the regulation of cell senescence by regulating apoptosis, energy metabolism, DNA repair, etc (Salih & Brunet, 2008 ). The expression of FOXO1 was significantly decreased in the liver (Tomobe et al., 2013 ) and aorta (Zhu et al., 2021 ) of SAMP8 aging mice and normal aging mice, respectively. We next tested whether FOXO1 expression might change in macrophages during aging.…”

“…It is reported that FOXO1 participates in the regulation of cell senescence by regulating apoptosis, energy metabolism, DNA repair, etc (Salih & Brunet, 2008). The expression of FOXO1 was significantly decreased in the liver (Tomobe et al, 2013) and aorta (Zhu et al, 2021) Interestingly, no significant alteration of FOXO1 mRNA level was observed in the process (Figure 2e). We hypothesized that the changes of FOXO1 protein level were due to post-translational modifications, including phosphorylation and dephosphorylation (Kamoshita et al, 2022).…”