Relaxin inhibits early steps in vascular inflammation

Regul Pept. 2011 Jan 17;166(1-3):76-82. doi: 10.1016/j.regpep.2010.09.001. Epub 2010 Sep 17.


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.

MeSH terms

  • Aorta
  • Cell Adhesion / drug effects
  • Chemokine CCL2 / biosynthesis
  • Down-Regulation
  • E-Selectin / biosynthesis
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / 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


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