Abstract
BackgroundIn 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.MethodsThe 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.ResultsAs 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.ConclusionsOur 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.
Highlights
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
Atherosclerosis as an immuno-inflammatory disease has been associated with a prevalent T-helper (Th) 1 response, being the Interferon-γ (IFN-γ) a key cytokine for proinflammatory response amplification; controversial, data support an antiatherogenic effect of Th2 responses, and Interleukin (IL)-4, the prototypic Th2-related cytokine, is generally considered as an anti-inflammatory cytokine [2]
The effects of statins seem to influence pathways leading to Ang Angiotensin II (II)-mediated atherosclerosis and we previously demonstrated, in circulating neutrophils of highcardiovascular risk patients, interferences of treatment on both Angiotensin II (Ang II) type-1 receptor (AT1R) expression and the cell membrane translocation Rac 1, a guanosine triphosphate–binding protein playing a key role in Ang II–operated signaling pathways [12]
Summary
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. Angiotensin II (Ang II) exerts its effects through the binding of two major receptors: the Ang II type-1 receptor (AT1R) which mediates the majority of the pro-atherogenic well-known Ang II actions and type-2 receptor (AT2R) that is considered counteracting the AT1R-mediated effects [3]. Little is known at present about the involvement of AT2Rs in atherosclerosis, these receptors appear to participate importantly in vascular biology with improvement in resistance artery remodeling and appear to be cardioprotective [6,7,8]
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