Russian Journal of ImmunologyRussian Journal of ImmunologyРоссийский иммунологический журнал1028-72212782-7291Russian Society of Immunology1733210.46235/1028-7221-17332-IBPORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИUnknownINTERACTION BETWEEN PRO-INFLAMMATORY CYTOKINES AND NOS3 GENE EXPRESSION IN POST-COVID-19 INDIVIDUALShttps://orcid.org/0000-0002-4683-5746Reddy KandukuriEswar
India

(MSc);

Research Scholar, Department of Biochemistry Meenakshi Academy of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, India.

Kandukurieswarreddy@gmail.comhttps://orcid.org/0000-0002-5474-0034JosephineAnthony
India

(Ph.D);

Scientist, Central Research Laboratory, Department of Research, Meenakshi Academy of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, India.

ajosephineanthony@gmail.comAnithaGandla
India

(MBBS, MD);

Professor and HOD, Department of Biochemistry, Fathima Institute of Medical Sciences, Kadapa-516 003, Andhra Pradesh, India

gandlaanitha129@gmail.comSurekaVaralakshmi
India

(Ph.D);

Registrar, Meenakshi Academy of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, India.

surekaramesh.v@gmail.comRamachandranIlangovan
India

(Ph.D);

Assistant Professor, Department of Endocrinology, DR. ALMPGIBMS University of Madras, Taramani Campus, Chennai, Tamil Nadu, India.

ilangovan2000@yahoo.comPuthiya PurayilRajitha
India

(MSc);

Research Scholar, Department of Anatomy, Meenakshi Academy of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, India.

rajithapp81@gmail.comRamachandranRenjitha
India

(MSc);

Research Scholar, Department of Pathology and Molecular Biology, Meenakshi Academy of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, India.

renjitharanjit@gmail.comVijayanVineetha
India

(MSc);

Research Scholar, Department of Pathology and Molecular Biology, Meenakshi Academy of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, India.

vineethavijayan09@gmail.comRoy DivakaranDinesh
India

(Ph.D);

CEO & Senior Cytogeneticist, Department of Cytogenetics, Genetika, Centre for Advanced Genetic Studies, Thiruvananthapuram-695035, Kerala, India.

drdineshroyd@gmail.comMeenakshi Academy of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, IndiaFathima Institute of Medical Sciences, Andhra Pradesh, IndiaDR. ALMPGIBMS University of Madras, Taramani Campus, Chennai, Tamil Nadu, IndiaCEO & Senior Cytogeneticist, Genetika, Centre for Advanced Genetic Studies, Kerala, India121120251010202511112025Copyright ©; , Reddy Kandukuri E., Josephine A., Anitha G., Sureka V., Ramachandran I., Puthiya Purayil R., Ramachandran R., Vijayan V., Roy Divakaran D.Copyright ©; , Reddy Kandukuri E., Josephine A., Anitha G., Sureka V., Ramachandran I., Puthiya Purayil R., Ramachandran R., Vijayan V., Roy Divakaran D.Reddy Kandukuri E., Josephine A., Anitha G., Sureka V., Ramachandran I., Puthiya Purayil R., Ramachandran R., Vijayan V., Roy Divakaran D.Reddy Kandukuri E., Josephine A., Anitha G., Sureka V., Ramachandran I., Puthiya Purayil R., Ramachandran R., Vijayan V., Roy Divakaran D.https://creativecommons.org/licenses/by/4.0https://rusimmun.ru/jour/article/view/17332

ObjectiveTo investigate the molecular mechanisms of endothelial dysfunction in post-COVID individuals by analyzing NOS3 gene expression and its association with pro-inflammatory cytokine profiles (IL-6, IL-18, TNF-α), thereby identifying potential biomarkers of early vascular impairment.MethodologyThis case-control study involved 240 participants: COVID-positive diabetics (Group 2), COVID-positive prediabetics (Group 1), COVID-negative diabetics (Group 4), COVID-negative prediabetics (Group 5), and healthy controls (Group 3). Blood samples were analyzed for biochemical parameters, cytokine levels (IL-6, IL-18, IL-1β, TNF-α) using the ELISA method, and NOS3 gene expression using RT-PCR, with expression levels normalized to GAPDH and calculated using the 2−ΔΔCt method. Statistical analysis was performed using Stata 17.0.ResultThe study showed that COVID-positive prediabetic and diabetic groups had the highest inflammatory and NOS3 levels, while COVID-negative non-diabetics had the lowest. ROC analysis identified TNF-α (AUC 0.85, p < 0.001) and IL-6 (AUC 0.84, p < 0.001) as the strongest classifiers. Scatter plots demonstrated significant positive correlations between NOS3 expression and IL-1β, IL-18, IL-6, and TNF-α (all p < 0.01). Logistic regression confirmed IL-18 (adjusted OR 10.30, p < 0.01), IL-6 (adjusted OR 4.05, p < 0.05), and TNF-α (adjusted OR 9.89, p < 0.01) as independent predictors, while IL-1β was not significant (p > 0.05).ConclusionOur study demonstrates a novel inflammatory–endothelial interaction in prediabetes, with elevated IL-1β, IL-18, IL-6, TNF-α, and NOS3 expression, most pronounced in COVID-positive groups. Notably, this is the first evidence of NOS3 upregulation in prediabetes, suggesting early endothelial adaptation to inflammatory stress, with IL-18, IL-6, and TNF-α emerging as strong predictors of NOS3 dysregulation. These findings highlight IL-6 and TNF-α as potential early biomarkers and position NOS3 as a novel indicator of endothelial dysfunction, offering new insight into immuno-metabolic pathways that link inflammation, glycemic status, and vascular risk.

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