RESUMO
Background: Correlations between posttranslational modifications and atrial fibrillation (AF) have been demonstrated in recent studies. However, it is still unclear whether and how ubiquitylated proteins relate to AF in the left atrial appendage of patients with AF and valvular heart disease. Methods: Through LC-MS/MS analyses, we performed a study on tissues from eighteen subjects (9 with sinus rhythm and 9 with AF) who underwent cardiac valvular surgery. Specifically, we explored the ubiquitination profiles of left atrial appendage samples. Results: In summary, after the quantification ratios for the upregulated and downregulated ubiquitination cutoff values were set at >1.5 and <1:1.5, respectively, a total of 271 sites in 162 proteins exhibiting upregulated ubiquitination and 467 sites in 156 proteins exhibiting downregulated ubiquitination were identified. The ubiquitylated proteins in the AF samples were enriched in proteins associated with ribosomes, hypertrophic cardiomyopathy (HCM), glycolysis, and endocytosis. Conclusions: Our findings can be used to clarify differences in the ubiquitination levels of ribosome-related and HCM-related proteins, especially titin (TTN) and myosin heavy chain 6 (MYH6), in patients with AF, and therefore, regulating ubiquitination may be a feasible strategy for AF.
RESUMO
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.
