Effects of serum amyloid a and lysophosphatidylcholine on intracellular calcium concentration in human coronary artery smooth muscle cells.
Effects of serum amyloid a and lysophosphatidylcholine on intracellular calcium concentration in human coronary artery smooth muscle cells.
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DOI：
10.1536/ihj.52.185
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发表时间：
2011
影响因子：
1.5
通讯作者：
Tomofumi Tanaka;Ken'ichi Ikeda;Yumiko Yamamoto;H. Iida;Hironobu Kikuchi;T. Morita;T. Yamasoba;R. Nagai;T. Nakajima
中科院分区：
文献类型：
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作者：
Tomofumi Tanaka;Ken'ichi Ikeda;Yumiko Yamamoto;H. Iida;Hironobu Kikuchi;T. Morita;T. Yamasoba;R. Nagai;T. Nakajima
血清淀粉样蛋白 A (SAA)（一种急性期蛋白）和溶血磷脂酰胆碱 (LPC)（一种氧化 LDL 成分）有助于动脉粥样硬化和心血管疾病的生理过程。然而，SAA/LPC 对人冠状动脉平滑肌细胞 (hCASMC) 的影响尚未得到充分研究。因此，我们研究了SAA/LPC对hCASMCs中Ca(2+)/Mg(2+)动员的影响及其潜在机制。使用fura-2 AM/mag-fura-2 AM测量细胞内Ca(2+)/Mg(2+)浓度([Ca(2+)](i)/[Mg(2+)](i))。还进行了常规 RT-PCR 分析。 SAA和LPC均通过Ca(2+)进入增加[Ca(2+)](i)。 SAA 诱导的 Ca(2+) 内流可被 Gd(3+)、SKF96365 和非选择性瞬时受体电位 (TRP) 通道阻滞剂 2-氨基乙氧基二苯硼酸盐 (2-APB) 抑制，但硝苯地平则不能。 LPC 诱导的 Ca(2+) 内流被 Gd(3+) 阻断，但硝苯地平、SKF96365 和 2-APB 不阻断。 U-73122 和 PTX 阻止 SAA- 的激活，但不能阻止 LPC 诱导的 Ca(2+) 流入。 LPC（而非SAA）增加[Mg(2+)](i) 和[Ca(2+)](i)。 RT-PCR 分析显示 TRPC1/4、TRPV1/2/4 和 TRPM7/8 mRNA 的表达。这些结果表明SAA/LPC激活hCASMCs中的Ca(2+)内流； SAA 通过 PTX 敏感的 G 蛋白、PLC 和 TRPC 途径激活它，而 LPC 独立于这些途径激活它，TRPM7 可能部分参与其中。因此，TRP蛋白似乎是SAA/LPC诱导的hCASMCs中Ca(2+)信号传导的靶分子，其可能在动脉粥样硬化等病理生理和炎症条件下的冠状肌功能障碍中发挥作用。
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.