This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 29/12/2146    most recent ATVBAHA.109.194134v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Jamaluddin, M. S. Articles by Chen, C. PubMed PubMed Citation Articles by Jamaluddin, M. S. Articles by Chen, C.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:2146.)
© 2009 American Heart Association, Inc.

Cell Biology/Signaling

Eotaxin Increases Monolayer Permeability of Human Coronary Artery Endothelial Cells

Md Saha Jamaluddin; Xinwen Wang; Hao Wang; Cubas Rafael; Qizhi Yao; Changyi Chen

From the Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex.

Correspondence to Changyi (Johnny) Chen, MD, PhD, Michael E. DeBakey Department of Surgery (R413), Baylor College of Medicine, One Baylor Plaza, Mail stop: BCM 391, Houston, TX 77030. E-mail jchen{at}bcm.tmc.edu

Objective— The objective of this study was to determine the effects and molecular mechanisms of eotaxin, a newly discovered chemokine (CCL11), on endothelial permeability in the human coronary artery endothelial cells (HCAECs).

Methods and Results— Cells were treated with eotaxin, and the monolayer permeability was studied by using a costar transwell system with a Texas Red–labeled dextran tracer. Eotaxin significantly increased monolayer permeability in a concentration-dependent manner. In addition, eotaxin treatment significantly decreased the mRNA and protein levels of endothelial junction molecules including zonula occludens-1 (ZO-1), occludin, and claudin-1 in a concentration-dependent manner as determined by real-time RT-PCR and Western blot analysis, respectively. Increased oxidative stress was observed in eotaxin-treated HCAECs by analysis of cellular glutathione levels. Furthermore, eotaxin treatment substantially activated the phosphorylation of MAPK p38. HCAECs expressed CCR3. Consequently, antioxidants (ginkgolide B and MnTBAP), specific p38 inhibitor SB203580, and anti-CCR3 antibody effectively blocked the eotaxin-induced permeability increase in HCAECs. Eotaxin also increased the phosphorylation of Stat3 and nuclear translocation of NF-B in HCAECs.

Conclusions— Eotaxin increases vascular permeability through CCR3, the downregulation of tight junction proteins, increase of oxidative stress, and activation of MAPK p38, Stat3, and NF-kB pathways in HCAECs.

Eotaxin, a newly discovered chemokine (CCL11), significantly increases vascular permeability through the downregulation of tight junction proteins, increase of oxidative stress, and activation of MAPK p38, Stat3, and NF-B in human coronary artery endothelial cells, suggesting an important role for eotaxin in endothelial dysfunction during the vascular lesion formation.

Key Words: endothelial permeability • HCAEC • eotaxin • tight junction molecules • oxidative stress • ginkgolide B • MAPK p38