Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Research Cardiology 2011;118:107–115 DOI: 10.1159/000327547 1 ,25-Dihydroxyvitamin D 3 Attenuates Platelet Activation and the Expression of VCAM-1 and MT1-MMP in Human Endothelial Cells Ksenija Stach   a Anna-Isabelle Kälsch   b Xuan Duc Nguyen   c Elif Elmas   a Stefan Kralev   a Siegfried Lang   a Christel Weiss   d Martin Borggrefe   a Thorsten Kälsch   a   a  1st Department of Medicine, b  5th Department of Medicine, c  Institute of Transfusion Medicine and Immunology, and d  Department of Medical Statistics, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany cantly reduced through preincubation with 1 ,25-dihy- droxyvitamin D 3 . Platelets in direct contact with preincubat- ed endothelial cells showed significantly reduced CD62P expression when compared to platelets incubated with un- treated endothelial cells. Conclusions: 1 ,25-Dihydroxyvi- tamin D 3 attenuates platelet activation and the expression of VCAM-1 and MT1-MMP in human endothelial cells and could have early therapeutic relevance in atherosclerotic diseases. Copyright © 2011 S. Karger AG, Basel Introduction Atherosclerosis is considered a chronic inflammatory disease [1–4] and is associated with endothelial dysfunc- tion and other profound changes in the vascular system [4, 5]. Activated platelets, endothelial cells and locally re- leased cytokines play a prominent role in the initiation and progression of atherosclerosis under chronic inflam- Key Words Platelets  1 ,25-Dihydroxyvitamin D 3  Inflammation  Atherosclerosis  Endothelial cells Abstract Objective: Inflammatory conditions contribute to increased expression of various activity markers in platelets and endo- thelial cells, leading to atherosclerotic changes in the vascu- lar wall. The objective of this study was to investigate possi- ble protective effects of 1 ,25-dihydroxyvitamin D 3 in an endothelial cell model. Methods: After a 24-hour incubation with 1 ,25-dihydroxyvitamin D 3 , human umbilical vein en- dothelial cells were stimulated with lipopolysaccharide (LPS) and incubated in direct contact with platelets. The expres- sion of CD40L and CD62P in platelets, the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (VCAM-1), the urokinase receptor uPAR and membrane type 1 matrix metalloproteinase (MT1-MMP) in endothelial cells and endothelial cell reactive oxygen spe- cies generation were measured by flow cytometry. Endo- thelial nitric oxide synthase was analyzed by Western blot. Results: The increased expression of VCAM-1 and MT1-MMP in endothelial cells by proinflammatory stimulation with LPS and by direct contact with activated platelets was signifi- Received: December 24, 2010 Accepted after revision: March 11, 2011 Published online: May 5, 2011 Thorsten Kälsch, MD, PhD University Medical Centre Mannheim, 1st Department of Medicine Medical Faculty Mannheim, University of Heidelberg Theodor-Kutzer-Ufer 1–3, DE–68167 Mannheim (Germany) Tel. +49 62 1383 2204, E-Mail thorsten.kaelsch  @  umm.de or T.Kaelsch  @  yahoo.de © 2011 S. Karger AG, Basel 0008–6312/11/1182–0107$38.00/0 Accessible online at: www.karger.com/crd K.S. and A.-I.K. contributed equally to this work. Downloaded by: Radboud Universiteit Nijmegen 131.174.75.30 - 11/22/2013 9:54:44 PM