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Circulating SLC17A5 as a Diagnostic Biomarker of Early Endothelial Dysfunction in Young Dyslipidemic Individuals
Shamima Akhtar1,2, Komal Sagar3, Milind P Hote4
1Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Room No. 3048, Ansari Nagar, New Delhi, 110029, India. ashamima05@gmail.com.
Insights
Circulating sialin mRNA shows diagnostic potential for endothelial dysfunction. This novel biomarker, elevated in dyslipidemic individuals, offers high sensitivity and specificity for identifying endothelial activation.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Research
Background:
- Endothelial dysfunction is a key factor in cardiovascular diseases like coronary artery disease (CAD).
- Identifying reliable biomarkers for early detection of endothelial activation is crucial for timely intervention.
- Current diagnostic methods may not fully capture the dynamic nature of endothelial dysfunction.
Purpose of the Study:
- To investigate the diagnostic potential of sialin mRNA as a biomarker for endothelial dysfunction.
- To compare sialin mRNA levels in patients with CAD, dyslipidemia (DLP), and healthy controls (HC).
- To explore the regulatory mechanisms of sialin mRNA expression in endothelial cells.
Main Methods:
- Quantification of sialin and CXCL14 mRNA in serum samples from CAD patients, DLP individuals, and HC.
- In vitro stimulation of human umbilical vein endothelial cells (HUVECs) with TNFα or AT-2.
- Analysis of sialin mRNA expression kinetics post-stimulation using Real-time PCR and ELISA.
- In silico analysis to identify potential regulatory elements of sialin mRNA.
Main Results:
- Sialin mRNA expression was significantly increased in TNFα or AT-2 stimulated endothelial cells.
- Serum sialin mRNA levels were markedly higher in DLP patients compared to HC and CAD patients.
- Elevated CXCL14 mRNA was observed in CAD patients.
- Receiver operating characteristic (ROC) curve analysis indicated high sensitivity and specificity of sialin mRNA for predicting endothelial dysfunction.
- In silico analysis suggested binding of translational repressor RNPs to the 5'UTR of sialin mRNA.
Conclusions:
- Circulating sialin mRNA serves as a novel and sensitive biomarker for endothelial activation.
- Sialin mRNA levels can differentiate between healthy individuals and those with dyslipidemia or CAD.
- This finding opens new avenues for non-invasive diagnostics of endothelial dysfunction and related cardiovascular conditions.
Abstract:
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.
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