Angiotensin II type 1 and type 2 receptor expression in circulating monocytes of diabetic and hypercholesterolemic patients over 3-month rosuvastatin treatment

12noneBackground: In diabetes, a variety of pro-inflammatory cellular changes has been found in various cell types, including monocytes which are known to be involved in all the phases of atherogenesis. Angiotensin II (Ang II) type 1 receptor (AT(1)R) mediates the pro-atherogenic effects of Ang II whereas the type 2 receptor (AT(2)R) seems associated with atheroprotection. We sought to investigate the potential changes of AT(1)R-AT(2)R expression in human monocytes of type 2 diabetic-hypercholesterolemic patients and in hypercholesterolemic subjects, upon clinical treatment with rosuvastatin. Methods: The AT(1)R membrane protein and mRNA AT1R and AT2R expression in monocytes were investigated in 10 type 2 diabetic-hypercholesterolemic patients and in 10 hypercholesterolemic subjects, before and after 3-month rosuvastatin treatment. Moreover, the serum cytokine levels of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were detected. Results: As expected, rosuvastatin was associated with a change in the lipid profile in the two groups. Both the membrane protein (P = 0.008) and the AT(1)R mRNA expression (P = 0.038) were significantly reduced during treatment in the absence of AT(2)R expression change in diabetic-hypercholesterolemic patients whereas no significant difference was observed in hypercholesterolemic subjects. The serum IL-4 levels were increased during treatment whereas no change was observed in IFN-gamma in diabetic-hypercholesterolemic patients. No cytokine change was observed in hypercholesterolemic subjects. Conclusions: Our study on monocytes of diabetic-hypercholesterolemic patients, showing a reduced AT(1)R but not AT(2)R expression during rosuvastatin treatment, suggests that statin therapy may modulate favorably the AT(1)-AT(2) receptor balance in subjects with coexistent type 2 diabetes.Marino, F.; Maresca, A.M.; Cosentino, M.; Castiglioni, L.; Rasini, E.; Mongiardi, C.; Maio, R.C.; Legnaro, M.; Schembri, L.; Dentali, F.; Grandi, A.M.; Guasti, L.Marino, Franca; Maresca, ANDREA MARIA; Cosentino, Marco; Castiglioni, L.; Rasini, E.; Mongiardi, C.; Maio, R. C.; Legnaro, M.; Schembri, L.; Dentali, Francesco; Grandi, ANNA MARIA; Guasti, Luigin

Right ventricular remodelling in mild hypertensive patients: role of left ventricular morpho-functional parameters

Previous studies suggested that hypertensive patients with left ventricular (LV) hypertrophy display right ventricular (RV) remodelling. Few data are available about RV remodelling in naive hypertensives without severe cardiac organ damage. Our aim was to evaluate the relationship between RV and LV morpho-functional parameters in never-treated patients with grade 1 hypertension and whether central blood pressure (CBP), inflammatory and metabolic parameters are potentially associated with RV remodelling. 150 never-treated subjects without evidence of diabetes or other cardiovascular diseases were enrolled in our study. We recruited 100 patients with mild hypertension (twenty-four hours blood pressure (24 h BP) 65 130/80 mmHg) and 50 normotensive subjects matched for gender, age and body mass index. To estimate the LV/RV parameters, we performed echography as well as arterial tonometry to assess pulse wave analysis/velocity (PWA/PWV). We found 24 h BP, CBP and PWV were higher in hypertensive patients than in normotensives. In addition, LV mass index was higher in hypertensives, and greater RV free wall thickness was observed (5.3 \ub1 1.4 vs 4.6 \ub1 1.2 mm, P = 0.02). RV thickness correlated with interventricular septum (IVS), systolic CBP and RV E\u2032 (r = 0.50, P = 0.0001, r = 0.30, P = 0.003, r = 120.24, P = 0.015); linear regression analysis showed a correlation with only IVS (\u3b2 = 0.39, P = 0.001). RV E\u2032 was correlated with IVS, LV E\u2032 and systolic CBP (r = 120.35, P = 0.0001, r = 0.25, P = 0.012, r = 120.24, P = 0.019); the correlation with IVS and LV E\u2032 (\u3b2 = 120.310, P = 0.001; \u3b2 = 0.27, P = 0.004) was confirmed by linear regression analysis. Our study shows RV remodelling is mostly correlated with IVS thickness, supporting the ventricular interdependence hypothesis

sRAGE and early signs of cardiac target organ damage in mild hypertensives

Soluble Receptor for Advanced Glycation End Products (sRAGE) may be considered a marker inversely related to inflammation and its participation has been established in patients with advanced atherosclerotic vascular diseases. However, it is still unknown whether sRAGE reduction could be early metabolic change in the first stage of hypertension and initial hypertension-associated cardiac damage. We sought to determine the sRAGE values in otherwise healthy, untreated and recently diagnosed mild hypertensives and evaluate their association with blood pressure (BP) values, metabolic parameters, and with subclinical initial signs of cardiac target organ damage (TOD).Background: Soluble Receptor for Advanced Glycation End Products (sRAGE) may be considered a marker inversely related to inflammation and its participation has been established in patients with advanced atherosclerotic vascular diseases. However, it is still unknown whether sRAGE reduction could be early metabolic change in the first stage of hypertension and initial hypertension-associated cardiac damage. We sought to determine the sRAGE values in otherwise healthy, untreated and recently diagnosed mild hypertensives and evaluate their association with blood pressure (BP) values, metabolic parameters, and with subclinical initial signs of cardiac target organ damage (TOD). Methods: sRAGE were measured in 100 hypertensive and 100 normotensive subjects matched for age, gender and body mass index (BMI), submitted to a clinic visit and both ambulatory BP monitoring and echocardiography to determine the presence of initial cardiac TOD (presence of signs of left ventricular hypertrophy: left ventricular mass indexed for height 2.7 (LVMi) > 48 g/m 2.7 for men and > 44 g/m 2.7 for women and/or increased left atrial volume 4-chamber indexed for body surface area (LAVi) > 34 ml/m 2 ). Results: sRAGE levels were similar between hypertensive and normotensive subjects and were not significantly correlated with office and 24-h BPs values. However, when subgrouping the hypertensive patients in Hyp-TOD and Hyp-withoutTOD, sRAGE was found to be different among the three groups (p = 0.030), being lower in the Hyp-TOD group than the values of both Hyp-withoutTOD (p = 0.038) and normotensives (p = 0.038). In hypertensive patients sRAGE was negatively related with both LVMi (r = 12 0.239, p = 0.034) and LAVi (r = 12 0.315, p = 0.005) and was independently related to cardiac TOD also in multivariable analysis. Conclusions: In this population of mild hypertensives, low circulating sRAGE may be a very early marker of initial TOD, suggesting the possible participation of oxidative stress in initial cardiac changes in human hypertension