Relaxin inhibits early steps in vascular inflammation.
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.
Brecht
Anna
A
Department of Cardiology and Angiology, Charité-- University Medicine Berlin, Berlin, Germany. anna.brecht@charite.de
Bartsch
Cornelia
C
Baumann
Gert
G
Stangl
Karl
K
Dschietzig
Thomas
T
D001011:Aorta; D002448:Cell Adhesion / Q000187:drug effects; D018932:Chemokine CCL2 / Q000096:biosynthesis; D015536:Down-Regulation; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D039441:Integrin alpha4 / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D054390:Receptors, CCR2 / Q000096:biosynthesis; D012065:Relaxin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D018932:Chemokine CCL2; D019040:E-Selectin; D054390:Receptors, CCR2; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4; D012065:Relaxin