Graphical Abstract Highlights d The SMUG1-DNA glycosylase promotes maturation of the telomeric DNA component, hTERC d SMUG1 regulates the presence of base modifications in hTERC d SMUG1 promotes DKC1 binding and stability of hTERC d hTERC levels limit telomerase activity in human SMUG1knockout cells
Background and aims: Atherogenesis involves a complex interaction between immune cells and lipids, processes greatly influenced by the vascular smooth muscle cell (VSMC) phenotype. The DNA glycosylase NEIL3 has previously been shown to have a role in atherogenesis, though whether this is due to its ability to repair DNA damage or to other non-canonical functions is not yet clear. Hereby, we investigate the role of NEIL3 in atherogenesis, specifically in VSMC phenotypic modulation, which is critical in plaque formation and stability. Methods: Chow diet-fed atherosclerosis-prone Apoe − /− mice deficient in Neil3, and NEIL3-abrogated human primary aortic VSMCs were characterized by qPCR, and immunohistochemical and enzymatic-based assays; moreover, single-cell RNA sequencing, mRNA sequencing, and proteomics were used to map the molecular effects of Neil3/NEIL3 deficiency in the aortic VSMC phenotype. Furthermore, BrdU-based proliferation assays and Western blot were performed to elucidate the involvement of the Akt signaling pathway in the transdifferentiation of aortic VSMCs lacking Neil3/NEIL3. Results: We show that Neil3 deficiency increases atherosclerotic plaque development without affecting systemic lipids. This observation was associated with a shift in VSMC phenotype towards a proliferating, lipidaccumulating and secretory macrophage-like cell phenotype, without changes in DNA damage. VSMC
Thirty-one brands of margarines from the Greek market were analyzed for their fatty acid composition including trans-fatty acids by gas chromatography. Trans fatty acids (TFAs) were found within the range of 0.16-0.97% of total fat content, with no sample found to have TFA in a concentration more than 1% of the total fat content. Increased levels of either saturated or cis-unsaturated was observed in each brand. Saturated, cis-monounsaturated and cis-polyunsaturated were found in the ranges of 11.26-51.75%, 22.98-60.37% and 12.09-56.30% of total fat content respectively, with mean values of 30.81 ± 10.40%, 34.41 ± 10.46% and 34.28 ± 14.02% of total fat. The chemical analysis of Greek margarines over the past decades has indicated that the TFA content of Greek margarines has declined over the past 20 years by approximately 95%.
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