title: Lysophosphatidic acid induces shear stress-dependent Ca2+ influx in mouse aortic endothelial cells in situ.
abstract: Using real-time two-photon laser scanning microscopy, we have demonstrated that lysophosphatidic acid (LPA), a bioactive lipid mediator, causes shear stress-dependent oscillatory local increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in fluo-4-loaded endothelial cells of isolated mouse aortic strips in situ. The increase in [Ca(2+)](i) occurred independently in the individual endothelial cells in a stepwise manner or repetitively during constant flow. The percentage of cells that responded and the averaged level of increase in [Ca(2+)](i) were dependent on both the concentration of LPA (0.3-10 μm) and the shear stress (10-80 dyn cm(-2)). The response was inhibited by removing extracellular Ca(2+), but not by thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase. The spatiotemporal properties of the [Ca(2+)](i) response were completely different from those of a Ca(2+) wave induced by ATP, a Ca(2+)-mobilizing agonist. These results were almost the same as those in the previous investigation using cultured bovine aortic endothelial cells, and suggest that LPA enhanced the shear stress-induced oscillatory Ca(2+) influx, termed 'Ca(2+) spot', in endothelial cells via activation of elementary Ca(2+) influx. In conclusion, the present study demonstrates, for the first time, that LPA functions as an endogenous sensitizer for mechanotransduction in endothelial cells in shear conditions in aortic strips in situ as well as in cultured cells. This indicates an important role for LPA as an endogenous factor in fluid flow-induced endothelial function.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. ohata-h77@pharm.showa-u.ac.jp
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Ohata
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamada
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Momose
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D013314:Stress, Mechanical; D019284:Thapsigargin / Q000494:pharmacology; D014966:Xanthenes / Q000494:pharmacology
chemical_list: D000814:Aniline Compounds; C409648:Fluo 4; D008246:Lysophospholipids; D014966:Xanthenes; D019284:Thapsigargin; D000255:Adenosine Triphosphate; C032881:lysophosphatidic acid; D002118:Calcium