title: Effects of serum amyloid a and lysophosphatidylcholine on intracellular calcium concentration in human coronary artery smooth muscle cells.
abstract: Serum amyloid A (SAA), an acute-phase protein, and lysophosphatidylcholine (LPC), an oxidized LDL component, contribute to the physiological processes of atherosclerosis and cardiovascular disease. However, the effects of SAA/LPC on human coronary artery smooth muscle cells (hCASMCs) have not been fully investigated. Therefore, we examined the effects of SAA/LPC on Ca(2+)/Mg(2+) mobilization and its underlying mechanisms in hCASMCs. Intracellular Ca(2+)/Mg(2+) concentration ([Ca(2+)](i) / [Mg(2+)](i)) was measured with fura-2 AM/mag-fura-2 AM. Conventional RT-PCR analysis was also performed. Both SAA and LPC increased [Ca(2+)](i) by Ca(2+) entry. The SAA-induced Ca(2+) entry was inhibited by Gd(3+), SKF96365, and 2-aminoethoxydiphenyl borate (2-APB), a nonselective transient receptor potential (TRP) channel blocker, but not nifedipine. The LPC-induced Ca(2+) entry was blocked by Gd(3+), but not nifedipine, SKF96365 and 2-APB. U-73122 and PTX prevented the activation of SAA-, but not LPC-induced Ca(2+) influx. LPC, but not SAA, increased [Mg(2+)](i) as well as [Ca(2+)](i). The RT-PCR analysis revealed the expression of TRPC1/4, TRPV1/2/4, and TRPM7/8 mRNA. These results suggest that SAA/LPC activate Ca(2+) influx in hCASMCs; SAA activates it via PTX-sensitive G-protein, PLC and TRPC pathways, while LPC activates it independently of these pathways, where TRPM7 may be partly involved. Thus, TRP protein appears to be a target molecule of Ca(2+) signaling in hCASMCs elicited by SAA/LPC, which may play roles in coronary muscle dysfunction under pathophysiological and inflammatory conditions such as atherosclerosis.
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ikeda
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Haruko
authors.initials: H
authors.lastname: Iida
authors.forename: Hironobu
authors.initials: H
authors.lastname: Kikuchi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Morita
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamasoba
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D008244:Lysophosphatidylcholines / Q000378:metabolism* / Q000494:pharmacology*; D008274:Magnesium / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000378:metabolism* / Q000494:pharmacology*; D050052:TRPC Cation Channels / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D004963:Estrenes; D008244:Lysophosphatidylcholines; D011760:Pyrrolidinones; D000685:Serum Amyloid A Protein; D050052:TRPC Cation Channels; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D037342:Pertussis Toxin; D008274:Magnesium; D002118:Calcium