Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
Cardiovasc Diabetol. 2012 Dec 22;11:153. doi: 10.1186/1475-2840-11-153.
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 (AT1R) mediates the pro-atherogenic effects of Ang II whereas the type 2 receptor (AT2R) seems associated with atheroprotection. We sought to investigate the potential changes of AT1R-AT2R expression in human monocytes of type 2 diabetic- hypercholesterolemic patients and in hypercholesterolemic subjects, upon clinical treatment with rosuvastatin.
The AT1R 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-γ (IFN-γ) and interleukin-4 (IL-4) were detected.
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 AT1R mRNA expression (P = 0.038) were significantly reduced during treatment in the absence of AT2R 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-γ in diabetic-hypercholesterolemic patients. No cytokine change was observed in hypercholesterolemic subjects.
Our study on monocytes of diabetic-hypercholesterolemic patients, showing a reduced AT1R but not AT2R expression during rosuvastatin treatment, suggests that statin therapy may modulate favorably the AT1-AT2 receptor balance in subjects with coexistent type 2 diabetes.
在糖尿病中，已在各种细胞类型中发现了多种促炎细胞变化，包括单核细胞，已知其参与动脉粥样硬化形成的所有阶段。血管紧张素 II（Ang II）1 型受体（AT1R）介导 Ang II 的促动脉粥样硬化作用，而 2 型受体（AT2R）似乎与动脉粥样硬化保护有关。我们试图研究在临床用罗苏伐他汀治疗 2 型糖尿病伴高胆固醇血症患者和高胆固醇血症患者的单核细胞中，AT1R-AT2R 表达的潜在变化。
在 10 例 2 型糖尿病伴高胆固醇血症患者和 10 例高胆固醇血症患者中，在接受 3 个月的罗苏伐他汀治疗前后，研究了单核细胞中 AT1R 膜蛋白和 AT1R 和 AT2R 的 mRNA 表达。此外，还检测了血清细胞因子干扰素-γ（IFN-γ）和白细胞介素-4（IL-4）的水平。
正如预期的那样，罗苏伐他汀与两组的血脂谱变化有关。在没有 AT2R 表达变化的情况下，糖尿病伴高胆固醇血症患者的膜蛋白（P=0.008）和 AT1R mRNA 表达（P=0.038）均在治疗期间明显降低，而高胆固醇血症患者则无明显差异。在治疗过程中，血清 IL-4 水平升高，而糖尿病伴高胆固醇血症患者的 IFN-γ水平没有变化。高胆固醇血症患者没有观察到细胞因子变化。
我们对糖尿病伴高胆固醇血症患者单核细胞的研究表明，在罗苏伐他汀治疗期间，AT1R 表达减少而 AT2R 表达不变，提示他汀类药物治疗可能在合并 2 型糖尿病的患者中有利于调节 AT1-AT2 受体平衡。
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