Effect of lysophosphatidylglycerol on intracellular free Ca2+ concentration in A10 vascular smooth muscle cells

Abstract

Although plasma levels of lysophosphatidylglycerol (LPG) are increased in hypertension, its role in the pathogenesis of vascular defects is not clear. In view of the importance of Ca2+ overload in causing vascular smooth muscle (VSM) dysfunction, the action of LPG on [Ca2+]i in cultured A10 VSM cell line was examined by using Fura 2-AM acetoxymethyl ester technique. LPG was found to induce a concentration-dependent increase in [Ca2+]i in VSM cells. This change was dependent both on the extracellular and intracellular Ca2+ sources, as it was reduced by 30% by EGTA, an extracellular Ca2+ chelator, and 70% by thapsigargin, a sarcoplasmic reticulum (SR) Ca2+-pump inhibitor. However the increase in [Ca2+]i due to LPG was not altered by caffeine or ryanodine, which affect Ca2+-release through the ryanodine receptors in the SR. On the other hand, LPG-induced change in [Ca2+]i was suppressed by 2-nitro-4-carboxyphenyl N,N-diphenylcarbamate, a phospholipase C (PLC) inhibitor, as well as by xestospongin and 2-aminoethoxydiphenyl borate, two inositol trisphosphate (IP3) receptor inhibitors in the SR. These observations support the view that LPG-induced increase in [Ca2+]i in VSM cells is mainly a result of Ca2+ release from Ca2+ pool in the SR through PLC/IP3-sensitive signal transduction mechanism. Furthermore, it is suggested that the elevated level of LPG may induce intracellular Ca2+ overload and thus play a critical role in the development of vascular abnormalities.