PMID- 20851151 OWN - NLM STAT- MEDLINE DCOM- 20110328 LR - 20220318 IS - 1873-1686 (Electronic) IS - 0167-0115 (Linking) VI - 166 IP - 1-3 DP - 2011 Jan 17 TI - Relaxin inhibits early steps in vascular inflammation. PG - 76-82 LID - 10.1016/j.regpep.2010.09.001 [doi] AB - 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-alpha-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-alpha-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. CI - Copyright (c) 2010 Elsevier B.V. All rights reserved. FAU - Brecht, Anna AU - Brecht A AD - Department of Cardiology and Angiology, Charite-- University Medicine Berlin, Berlin, Germany. anna.brecht@charite.de FAU - Bartsch, Cornelia AU - Bartsch C FAU - Baumann, Gert AU - Baumann G FAU - Stangl, Karl AU - Stangl K FAU - Dschietzig, Thomas AU - Dschietzig T LA - eng PT - Journal Article DEP - 20100917 PL - Netherlands TA - Regul Pept JT - Regulatory peptides JID - 8100479 RN - 0 (Chemokine CCL2) RN - 0 (E-Selectin) RN - 0 (Receptors, CCR2) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 143198-26-9 (Integrin alpha4) RN - 9002-69-1 (Relaxin) SB - IM MH - Aorta MH - Cell Adhesion/drug effects MH - Chemokine CCL2/biosynthesis MH - Down-Regulation MH - E-Selectin/biosynthesis MH - Endothelium, Vascular/cytology/drug effects/metabolism MH - Humans MH - Inflammation/*prevention & control MH - Integrin alpha4/biosynthesis MH - Muscle, Smooth, Vascular/cytology MH - Receptors, CCR2/biosynthesis MH - Relaxin/*pharmacology MH - Tumor Necrosis Factor-alpha/pharmacology MH - Umbilical Veins MH - Vascular Cell Adhesion Molecule-1/biosynthesis EDAT- 2010/09/21 06:00 MHDA- 2011/03/29 06:00 CRDT- 2010/09/21 06:00 PHST- 2010/05/03 00:00 [received] PHST- 2010/08/22 00:00 [revised] PHST- 2010/09/13 00:00 [accepted] PHST- 2010/09/21 06:00 [entrez] PHST- 2010/09/21 06:00 [pubmed] PHST- 2011/03/29 06:00 [medline] AID - S0167-0115(10)00361-7 [pii] AID - 10.1016/j.regpep.2010.09.001 [doi] PST - ppublish SO - Regul Pept. 2011 Jan 17;166(1-3):76-82. doi: 10.1016/j.regpep.2010.09.001. Epub 2010 Sep 17.