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.