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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:e37.)
© 2003 American Heart Association, Inc.

Vascular Biology

Dominant Expression of the CysLT₂ Receptor Accounts for Calcium Signaling by Cysteinyl Leukotrienes in Human Umbilical Vein Endothelial Cells

Mattias Sjöström^*; Anne-Sofie Johansson^*; Oliver Schröder; Hong Qiu; Jan Palmblad; Jesper Z. Haeggström

From the Department of Medical Biochemistry and Biophysics (M.S., O.S., H.Q., J.Z.H.), Division of Chemistry 2, Karolinska Institutet, and the Center for Inflammation and Hematology Research (A.-S.J., J.P.), Department of Medicine, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden.

Correspondence to Jesper Z. Haeggström, MD, PhD, Department of Medical Biochemistry and Biophysics, Division of Chemistry 2, Karolinska Institutet, S-171 77 Stockholm, Sweden. E-mail jesper.haeggstrom{at}mbb.ki.se

Objective— The objective of the present study was to identify and characterize the cell-surface receptors on human umbilical vein endothelial cells (HUVECs) that transduce calcium transients elicited by cysteinyl leukotrienes (CysLTs), potent spasmogenic and proinflammatory agents with profound effects on the cardiovascular system.

Methods and Results— Using quantitative reverse transcription–polymerase chain reaction, we found that HUVECs abundantly express CysLT₂R mRNA in vast excess (>4000-fold) of CysLT₁R mRNA. Lipopolysaccharide, tumor necrosis factor-, or interleukin-1ß caused a rapid (within 30 minutes) and partially reversible suppression of CysLT₂R mRNA levels. Challenge of HUVECs with BAY u9773, a specific CysLT₂R agonist, triggered diagnostic Ca²⁺ transients. LTC₄ and LTD₄ are equipotent agonists, and their actions can be blocked by the dual-receptor antagonist BAY u9773, but not by the CysLT₁R-selective antagonist MK571.

Conclusions— HUVECs almost exclusively express the CysLT₂R. Furthermore, Ca²⁺ fluxes elicited by CysLT in these cells emanate from perturbation of the CysLT₂R, rather than the expected CysLT₁R. Hence, signaling events involving CysLT₂R might trigger functional responses involved in the critical components of LT-dependant vascular reactions, which in turn have implications for ischemic heart disease and myocardial infarction.

Key Words: leukotrienes • endothelial cells • receptors • inflammation • arteriosclerosis

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