Relaxin inhibits early steps in vascular inflammation.

Abstract

Increased expression of endothelial adhesion molecules, high levels of the monocyte chemoattractant protein-1 (MCP-1) and enhanced VLA4 integrin/VCAM-1 and CCR-2/MCP-1 interactions are initial steps in vascular inflammation. We sought to determine whether relaxin, a potent vasodilatory and anti-fibrotic agent, mitigates these early events compromising endothelial integrity. The effect of relaxin coincubation on the TNF-α-stimulated expression of the adhesion molecules VCAM-1, ICAM-1 and E-selectin; the MCP-1 expression by human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (HAoSMC); as well as on direct monocyte-endothelium cell adhesion was quantified by ELISA or adhesion assay. CCR-2 and PECAM expression on HUVEC and THP-1 monocytes was investigated by FACS analysis. Relaxin treatment suppressed significantly TNF-α-induced upregulation of VCAM-1 and PECAM, CCR-2, and MCP-1 levels and direct monocyte adhesion to HUVEC. Our findings identify relaxin as a promising inhibitory factor in early vascular inflammation. By attenuating the upregulation of VCAM-1, key adhesion molecule in early vascular inflammation, and of MCP-1, a chemokine pivotal to monocyte recruitment, relaxin decreased initial monocyte-endothelium contact. This may be of relevance for the prevention and treatment of atherosclerosis and of other pro-inflammatory states.

• Authors: Anna Brecht, Cornelia Bartsch, Gert Baumann, Karl Stangl, Thomas Dschietzig
• Journal: Regulatory peptides (Regul Pept) Vol. 166 Issue 1-3 Pg. 76-82 (Jan 17 2011) ISSN: 1873-1686 [Electronic] Netherlands
• PMID: 20851151 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• Chemokine CCL2
• E-Selectin
• Receptors, CCR2
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• Integrin alpha4
• Relaxin

Topics

• Aorta
• Cell Adhesion (drug effects)
• Chemokine CCL2 (biosynthesis)
• Down-Regulation
• E-Selectin (biosynthesis)
• Endothelium, Vascular (cytology, drug effects, metabolism)
• Humans
• Inflammation (prevention & control)
• Integrin alpha4 (biosynthesis)
• Muscle, Smooth, Vascular (cytology)
• Receptors, CCR2 (biosynthesis)
• Relaxin (pharmacology)
• Tumor Necrosis Factor-alpha (pharmacology)
• Umbilical Veins
• Vascular Cell Adhesion Molecule-1 (biosynthesis)