Association of beta-1 and beta-2 adrenoreceptor gene expression with cardiovascular remodeling parameters and biomarker profile in patients with resistant hypertension combined with coronary heart disease

Background. Beta-adrenoreceptors (β-AR) are a key component of the neurohumoral regulation of the cardiovascular system. Direct in vivo assessment of β-AR in the myocardium is challenging, making peripheral blood leukocytes an actively studied surrogate tissue. However, the informativeness of leukocyte β-AR gene expression (ADRB1 and ADRB2) remains debatable, especially in combined pathologies where remodeling of the β-adrenoreceptor apparatus may contribute to resistance to β-blockers. Aim: To determine the nature of the relationships between ADRB1 and ADRB2 gene expression in leukocytes and myocardium, as well as their associations with cardiovascular remodeling parameters, biomarkers of inflammation, fibrosis, endothelial dysfunction, and adipokine imbalance in patients with coronary heart disease (CHD) combined with resistant hypertension (RH). Material and Methods. A single-center open-label study was conducted, including 52 patients with RH combined with CHD referred for coronary artery bypass grafting. All patients underwent clinical and laboratory-instrumental examinations, and ADRB1 and ADRB2 gene expression was determined. Results. Direct quantitative correlations were found between myocardial ADRB1 gene expression and blood leptin levels (r=0.62; p=0.04) and A-wave peak by echocardiography (r=0.45; p=0.03). Leukocyte ADRB1 gene expression correlated with matrix metalloproteinase-2 (MMP-2) levels (r=0.48; p=0.04) and with mean 24-hour diastolic blood pressure (r=−0.33; p=0.02). Myocardial ADRB2 gene expression directly correlated with MMP-9 levels (r=0.75; p=0.03), tumor necrosis factor-alpha (r=0.71; p=0.04), and asymmetric dimethylarginine (r=0.78; p=0.02), and inversely correlated with left atrial size (r=−0.47; p=0.02). Leukocyte ADRB2 gene expression also showed direct correlations with MMP-9 levels (r=0.74; p=0.01) and inverse correlations with E-wave peak by echocardiography (r=−0.30; p=0.03). Conclusion. Expression of β1- and β2-adrenoreceptor genes in the myocardium and leukocytes of patients with CHD and RH correlates with increased left ventricular and arterial stiffness. The key mechanisms underlying this association are inflammation, fibrosis, endothelial dysfunction, and adipokine imbalance reflecting sympathetic overactivation. These data may add to the current understanding of heart failure pathogenesis in coexistent cardiovascular conditions and reinforce the hypothesis that β-AR expression may guide individualized β-blocker therapy, although this requires prospective confirmation