Endothelial and vascular smooth muscle cell dysfunction mediated by cyclophylin A and the atheroprotective effects of melatonin.

Abstract

AIMS:

This study evaluated the role of cyclophilin A (CyPA) in early phase of atherosclerosis and also examined the atheroprotective effects of melatonin due to its antioxidant properties.

MAIN METHODS:

APOE null mice at 6 and 15weeks of age were treated with melatonin at a dose of 0.1mg/kg/day or 10mg/kg/day. We evaluated both histopathological alterations in endothelial and vascular smooth muscle cells by CyPA and rolling mononuclear cell expression during the early phase of atherosclerosis development.

KEY FINDINGS:

Our study showed that CyPA expression increases and may modulate inflammatory cell adhesion and interleukin-6 expression inducing vascular smooth muscle cell migration and inflammatory cell extravasation in a time-dependent manner. Moreover, we observed an indirect atheroprotective effect of melatonin on vascular injury; it inhibited CyPA mediated inflammatory cell extravasation and oxidative stress.

SIGNIFICANCE:

The melatonin treatment may represent a new atheroprotective approach that contributes to reducing the early phase of atherosclerosis involving the rolling of monocytes, their passage to subendothelial space and inhibition of CyPA expression.

• Authors: Rita Rezzani, Gaia Favero, Alessandra Stacchiotti, Luigi Fabrizio Rodella
• Journal: Life sciences (Life Sci) Vol. 92 Issue 17-19 Pg. 875-82 (May 20 2013) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 23201430 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Apolipoproteins E
• Interleukin-6
• Cyclophilin A
• Melatonin

Topics

• Animals
• Antioxidants (administration & dosage, pharmacology)
• Apolipoproteins E (genetics)
• Atherosclerosis (pathology, prevention & control)
• Cell Adhesion
• Cell Movement (drug effects)
• Cyclophilin A (metabolism)
• Dose-Response Relationship, Drug
• Endothelial Cells (drug effects, pathology)
• Gene Expression Regulation
• Inflammation (drug therapy, pathology)
• Interleukin-6 (genetics)
• Male
• Melatonin (administration & dosage, pharmacology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Muscle, Smooth, Vascular (cytology, drug effects, pathology)
• Myocytes, Smooth Muscle (drug effects, pathology)
• Oxidative Stress (drug effects)
• Time Factors