O-GlcNAc transferase-mediated O-GlcNAcylation of CD36 against myocardial ischemia-reperfusion injuryZhao, Yan, Sun
et alTissue Cell (2025) 95, 102878
Abstract: CD36 affects lipid metabolism and is involved in the development of myocardial infarction (MI). O-GlcNAcylation is a promising therapeutic target for myocardial ischemia-reperfusion (I/R) injury. This study aimed to investigate the effects of CD36 on myocardial I/R injury and its O-GlcNAcylation. H9C2 cardiomyocytes were induced by hypoxia/reoxygenation (H/R), and phenotypes were evaluated using cell counting kit-8, EdU assay, flow cytometry, and TUNEL assay. The O-GlcNAcylation was evaluated by immunoprecipitation, immunoblotting, and cycloheximide chase assay. The role of CD36 in vivo was analyzed by TTC staining and TUNEL assay. The results showed that CD36 protein levels were downregulated in I/R rats and H/R-induced H9C2 cells. OGT and O-GlcNAcylation levels were decreased by H/R. Overexpression of CD36 or OGT promoted cell proliferation and inhibited apoptosis of H/R-treated cells. Moreover, OGT facilitated the O-GlcNAcylation of CD36 at S195 site and enhanced CD36 protein stability. Knockdown of CD36 abrogated the effects of cellular behaviors caused by OGT, and CD36 mutation at S195 site reversed the promotion of proliferation and lipid uptake and the inhibition of apoptosis induced by wild-type CD36. Additionally, overexpression of CD36 attenuated infarction and apoptosis in the myocardium of rats. In conclusion, OGT-mediated O-GlcNAcylation of CD36 attenuates myocardial I/R injury through promoting the proliferation and inhibiting apoptosis of cardiomyocytes. The findings suggest that targeting CD36 O-GlcNAcylation may be a promising therapy for MI.Copyright © 2025. Published by Elsevier Ltd.
Gut dysbiosis induced by a high-salt diet aggravates atherosclerosis by increasing the absorption of saturated fatty acids in ApoE-deficient miceYoshimura, Okamura, Yuge
et alJ Clin Biochem Nutr (2025) 76 (2), 210-220
Abstract: Excessive salt intake has been associated with gut dysbiosis and increased cardiovascular risk. This study investigates the role of gut dysbiosis induced by a high-salt diet in the progression of atherosclerosis in ApoE-deficient mice. Sixteen-week-old male ApoE-deficient mice were fed either a high-fat, high-sucrose diet or high-fat, high-sucrose diet supplemented with 4% NaCl for eight weeks. The group on the HFHSD with high salt showed significant progression of atherosclerosis compared to the high-fat, high-sucrose diet group. Analysis of the gut microbiota revealed reduced abundance of beneficial bacteria such as Allobaculum spp., Lachnospiraceae, and Alphaproteobacteria in the high-salt group. Additionally, this group exhibited increased expression of the Cd36 gene, a transporter of long-chain fatty acids, in the small intestine. Serum and aortic levels of saturated fatty acids, known contributors to atherosclerosis, were markedly elevated in the high-salt group. These findings suggest that a high-salt diet exacerbates atherosclerosis by altering gut microbiota and increasing the absorption of saturated fatty acids through upregulation of intestinal fatty acid transporters. This study provides new insights into how dietary salt can influence cardiovascular health through its effects on the gut microbiome and lipid metabolism.Copyright © 2025 JCBN.
Inherited Dyslipidemic Splenomegaly: A Genetic Macrophage Storage Disorder Caused by Disruptive Apolipoprotein E (APOE) VariantsFerreira, Oud, van der Crabben
et alGenes (Basel) (2025) 16 (3)
Abstract: Persistent splenomegaly, often an incidental finding, can originate from a number of inherited metabolic disorders (IMDs). Variants of APOE are primarily known as risk factors in terms of cardiovascular disease; however, severe dysfunction of APOE can result in a disease phenotype with considerable overlap with lysosomal storage disorders (LSDs), including splenomegaly and gross elevation of N-palmitoyl-O-phosphocholine-serine (PPCS).A case study (deep phenotyping, genetic and FACS analysis) and literature study was conducted.The index patient, with a family history of early-onset cardiovascular disease, presented with splenic infarctions in a grossly enlarged spleen. The identified genetic cause was homozygosity for two APOE variants (c.604C>T, p.(Arg202Cys) and c.512G>A, p.(Gly171Asp); ε1/ε1), resulting in a macrophage storage phenotype resembling an LSD that was also present in the brother of the index patient. A FACS analysis of the circulating monocytes showed increased lipid content and the expression of activation markers (CD11b, CCR2, CD36). This activated state enhances lipoprotein intake, which eventually converts these monocytes/macrophages into foam cells, accumulating in tissues (e.g., spleen and vascular wall). A literature search identified seven individuals with splenomegaly caused by APOE variants (deletion of leucine at position 167). The combined data from all patients identified male gender, splenectomy and obesity as potential modifiers determining the severity of the phenotype (i.e., degree of triglyceride increase in plasma and/or spleen size). Symptoms are (partially) reversible by lipid-lowering medication and energy restricted diets and splenectomy is contra-indicated.Inherited dyslipidemic splenomegaly caused by disruptive APOE variants should be included in the differential diagnoses of unexplained splenomegaly with abnormal lipid profiles. A plasma lipid profile consistent with dysbetalipoproteinemia is a diagnostic biomarker for this IMD.
Identification of potential modulators of intrauterine adhesion pathogenesis with RNA sequencing, histology and in vitro assaysLiu, Chen, Chi
et alGenomics (2025)
Abstract: Intrauterine adhesion (IUA), also referred to as intrauterine stenosis or synechiae, is a prevalent gynecological issue, which is characterized by the fusion of the walls of the intrauterine canal. However, the molecular changes during its pathogenesis are still unclear. In the present work, tissue samples from patients with IUA and normal endometrial tissues from healthy subjects were collected, and then RNA sequencing and bioinformatics analyses were performed to screen the differentially expressed genes (DEGs). Subsequently, immunohistochemistry was used for detecting the protein expression level of the representative genes including XDH, VNN1, CD36, and after transfection, enzyme-linked immunosorbent assay and Western blotting were used to evaluate their functions in regulating inflammatory response and the expression level of matrix metalloproteinases. It was revealed that multiple genes were dysregulated in the pathological tissues of patients with IUA, and these DEGs were associated with multiple biological processes and signal pathways including Hedgehog pathway. DEGs including XDH, VNN1, CD36 were also highly expressed in IUA tissues at protein level, and their expression levels correlated with the expression levels of inflammation mediators NLRP3 and STING. XHD, VNN1 and CD36 also promoted the expression and secretion of TNF-α, IL-1β and IL-6 in ishikawa cells, and up-regulated the expression level of MMP-2 and MMP-9. Collectively, our data suggested that Hedgehog signaling is a potential crucial pathway in IUA pathogenesis, and some DEGs contribute to endometrial fibrosis by regulating inflammatory response and matrix remodeling.Copyright © 2025. Published by Elsevier Inc.
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