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

Background: 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.