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<p>Diagnostic potential of sialin in identifying endothelial dysfunction is explored. 50 CAD patients, 50 young (20–35&#xa0;years) dyslipidemic individuals (DLP), and 50 healthy controls (HC) were included in the study. HUVECs were stimulated with either TNFα or AT-2. RNA isolation, Real-time PCR, ELISA, and immunofluorescence staining were performed. In silico analysis was performed. ROC curves were constructed. Stimulated ECs showed increased sialin mRNA expression. Sialin mRNA peaked in the supernatant at 1–6&#xa0;h, decreasing by 24&#xa0;h. Serum sialin mRNA was significantly higher in DLP patients than in HC and CAD patients, whereas CXCL14 mRNA was elevated in CAD patients. Sialin mRNA had high sensitivity/specificity for predicting endothelial dysfunction. In silico analysis revealed the binding of translational repressor RNPs to the 5’UTR of sialin mRNA. This is the first study highlighting circulating sialin mRNA as a novel biomarker for endothelial activation.</p> Graphical Abstract <p>Diagrammatic illustration of the role of sialin in early and late endothelial dysfunction. In early response to stressors, endothelial cells transcribe high copies of sialin mRNA, which is released to the extracellular milieu via exosomes after binding to the ribonucleoprotein (RBPs) whose synthesis is also elevated. These exosomal sialin mRNA might induce a signaling mechanism in the other cell types. In late endothelial dysfunction, sialin mRNA is increasingly translated to sialin protein, as RBPs binding to the sialin mRNA are decreased. Elevated sialin protein expression contributes to the decrease in cellular NO bioavailability by mediating nitrate efflux. CXCL14 mRNA is progressively released to the extracellular medium from dysfunctional endothelial cells.</p> <p></p>

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Circulating SLC17A5 as a Diagnostic Biomarker of Early Endothelial Dysfunction in Young Dyslipidemic Individuals

  • 期刊论文

  • 发表日期：

    2025年9月5日

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  • Shamima Akhtar,
  • Komal Sagar,
  • Milind P. Hote,
  • Ambuj Roy,
  • Savita Yadav,
  • Alpana Sharma

摘要

Diagnostic potential of sialin in identifying endothelial dysfunction is explored. 50 CAD patients, 50 young (20–35 years) dyslipidemic individuals (DLP), and 50 healthy controls (HC) were included in the study. HUVECs were stimulated with either TNFα or AT-2. RNA isolation, Real-time PCR, ELISA, and immunofluorescence staining were performed. In silico analysis was performed. ROC curves were constructed. Stimulated ECs showed increased sialin mRNA expression. Sialin mRNA peaked in the supernatant at 1–6 h, decreasing by 24 h. Serum sialin mRNA was significantly higher in DLP patients than in HC and CAD patients, whereas CXCL14 mRNA was elevated in CAD patients. Sialin mRNA had high sensitivity/specificity for predicting endothelial dysfunction. In silico analysis revealed the binding of translational repressor RNPs to the 5’UTR of sialin mRNA. This is the first study highlighting circulating sialin mRNA as a novel biomarker for endothelial activation.

Graphical Abstract

Diagrammatic illustration of the role of sialin in early and late endothelial dysfunction. In early response to stressors, endothelial cells transcribe high copies of sialin mRNA, which is released to the extracellular milieu via exosomes after binding to the ribonucleoprotein (RBPs) whose synthesis is also elevated. These exosomal sialin mRNA might induce a signaling mechanism in the other cell types. In late endothelial dysfunction, sialin mRNA is increasingly translated to sialin protein, as RBPs binding to the sialin mRNA are decreased. Elevated sialin protein expression contributes to the decrease in cellular NO bioavailability by mediating nitrate efflux. CXCL14 mRNA is progressively released to the extracellular medium from dysfunctional endothelial cells.