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

Abstract

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 (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.

METHODS:

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.

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 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.

CONCLUSIONS:

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.

• Authors: Franca Marino, Andrea Maria Maresca, Marco Cosentino, Luana Castiglioni, Emanuela Rasini, Christian Mongiardi, Ramona C Maio, Massimiliano Legnaro, Laura Schembri, Francesco Dentali, Anna Maria Grandi, Luigina Guasti
• Journal: Cardiovascular diabetology (Cardiovasc Diabetol) Vol. 11 Pg. 153 (Dec 22 2012) ISSN: 1475-2840 [Electronic] England
• PMID: 23259529 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Fluorobenzenes
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Pyrimidines
• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2
• Sulfonamides
• Rosuvastatin Calcium

Topics

• Aged
• Diabetes Mellitus, Type 2 (blood, complications, drug therapy, genetics)
• Female
• Fluorobenzenes (therapeutic use)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Hypercholesterolemia (blood, complications, drug therapy, genetics)
• Male
• Middle Aged
• Monocytes (metabolism)
• Pyrimidines (therapeutic use)
• Receptor, Angiotensin, Type 1 (blood, genetics)
• Receptor, Angiotensin, Type 2 (blood, genetics)
• Rosuvastatin Calcium
• Sulfonamides (therapeutic use)