Effect of high-fat on NOX4-SIRT1 signaling pathway in vascular aging
Shi Dandan
Liu Meixia
Liu Jiangang
Guo Xiaochen
Ning Ziqi
Zhang Yaoyao
Abstract：Objective To observe the alterations of protein expression of nicotinamide adenine di-nucleotide phosphatase oxidase 4-silent mating type information regulation 2 homolog 1(NOX4-SIRT1)signaling pathway in ApoE-/-mice and C57BL/6J mice induced by high-fat diet.Methods Twenty ApoE-/-mice and 40 C57BL/6J mice,aged of 10 weeks and half male and half female,were randomly divided into a NC group and a HFD group,with 10 mice in each group(ApoE-/-+NC and ApoE-/-+HFD groups,and C57+NC and C57+HFD groups).After 1 week of adaptive feed-ing period,each group was fed with their corresponding diet for subsequent 12 weeks,and then blood samples were collected from the anesthetized orbits and aortic arch tissues were harvested.HE staining and Masson staining were performed to examine the pathological morphology of the aortic arch tissues.The serum levels of TG,TC,HDL-C and LDL-C were measured using an auto-matic biochemical analyzer.The content of ox-LDLC was detected with ELISA,and the contents of ROS,GSH,GPX and NAD+were measured by colorimetry.The expression of SIRT1,p53,p21 and NOX4 was detected by Western blotting.Results Compared with the C57+NC group,the ApoE-/-+NC group showed significant lipid deposition,increased collagen fibers,elevated levels of TC,TG,HDLC,LDL-C,ox-LDL-C and ROS and increased p21 expression level,and obviously decreased contents of GSH,GPX and NAD+(P＜0.05,P＜0.01).Compared with the ApoE-/-+NC group,the ApoE-/-+HFD group showed larger plaque areas,lessened elastic fibers,more col-lagen fibers,increased levels of TC,HDL-C,LDL-C,ox-LDL-C and ROS,and p21 expression level(P＜0.01),and declined expression of GSH,GPX,NAD+and NOX4[6.4±0.8 μmol/L vs 9.6±0.8 μmol/L,242.0±39.0 U/ml vs 362.7±11.1 U/ml,0.61±0.15 nmol/L vs 1.07±0.20 nmol/L,0.26±0.01 vs 0.32±0.03;P＜0.05,P＜0.01[.Conclusion High-fat diet may accelerate vascular aging by elevating lipid and oxidative stress levels,decreasing NAD+and NOX4 expression,ele-vating p21 expression,and thereby activating the NOX4-SIRT1 pathway.
Keywords：diethigh-fatNADPH oxidase 4sirtuin 1apolipoproteins Emice
Publication Date：2025-07-15
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 871-876 )