Association of Monocyte Chemoattractant Protein-1 and Endothelin-1 Genes with Cardiac Pro-Β-Type Natriuretic Peptide...

Obesity and hypertension synergistically increase cardiovascular risk, with Monocyte Chemoattractant Protein-1 (MCP-1), Endothelin-1 (ET-1), and Pro-B-Type Natriuretic Peptide (Pro- BNP) implicated in vascular dysfunction and cardiac stress. However, their combined role in obesity-driven hypertension remains poorly understood. This study aimed to investigate the associations between MCP-1, ET-1, and Pro-BNP levels in obese hypertensive patients and evaluate their collective contribution to disease pathogenesis.

This prospective, non-randomized clinical study enrolled 97 adult male participants, stratified into four groups: healthy controls (n = 22), overweight normotensive individuals (n = 25), class I obese hypertensive patients (n = 25), and class II obese hypertensive patients (n = 25). Blood samples were collected and analyzed for metabolic parameters (fasting glucose, insulin, lipid profile), oxidative stress markers (MDA, GSH, SOD), and inflammatory cytokines (VEGF, IL-1β, IL-9). Gene expression levels of MCP-1, ET-1, and Pro-BNP were quantified using real-time PCR, while protein expression was assessed via Western blotting. Statistical analyses included one-way ANOVA with Bonferroni correction, Pearson correlation coefficients, and multivariable linear regression models adjusted for age, BMI, metabolic, and oxidative stress parameters.

Class II obese hypertensive patients exhibited the highest systolic and diastolic blood pressure, body mass index, and the most severe metabolic dysregulation, including elevated fasting glucose, insulin resistance, and dyslipidemia. Oxidative stress was significantly increased, as indicated by elevated MDA levels and reduced GSH and SOD activity. Inflammatory cytokines, including VEGF, IL-1β, and IL-9, were markedly elevated in this group. Gene and protein expression levels of Pro-BNP, ET-1, and MCP-1 were significantly upregulated in a stepwise manner across the groups, with class II patients showing the highest expression. Specifically, protein levels of Pro-BNP, ET-1, and MCP-1 were increased by 204.8%, 222.2%, and 180.6%, respectively, compared with healthy controls (all p < 0.05). Strong positive correlations were observed between Pro-BNP and both ET-1 and MCP-1 (r = 0.991, p < 0.001 for both). Receiver operating characteristic (ROC) analysis demonstrated high predictive accuracy for Pro-BNP (AUC = 0.94), ET-1 (AUC = 0.89), and MCP-1 (AUC = 0.92), with a combined biomarker panel achieving an AUC of 0.97.

The robust interrelationships among MCP-1, ET-1, and Pro-BNP suggest their synergistic involvement in promoting vascular inflammation, endothelial dysfunction, and cardiac stress in obesity-related hypertension. These biomarkers may serve as diagnostic indicators and therapeutic targets. Limitations include the male-only cohort and cross-sectional design.

The robust interrelationships among MCP-1, ET-1, and Pro-BNP suggest their synergistic involvement in promoting vascular inflammation, endothelial dysfunction, and cardiac stress in obesity-related hypertension. These biomarkers may serve as valuable diagnostic indicators and potential therapeutic targets. Further interventional studies are warranted to validate their clinical utility and explore targeted treatment strategies.