Raess B U, Porro R F, Tunnicliff G
Department of Pharmacology, Indiana University School of Medicine, Evansville 47712, USA.
Proc Soc Exp Biol Med. 1995 Sep;209(4):410-7. doi: 10.3181/00379727-209-43916.
Intracellular free calcium activity is in part determined by a calmodulin-regulated plasma membrane Ca(2+)-pump. Since changes in Ca2+ permeability have been implicated in atherosclerotic plaque formation, we initiated a lipid hyperalimentation protocol during which we measured various erythrocyte calcium flux parameters and early atheroma development. Adolescent New Zealand White rabbits were fed a diet with 0.5% cholesterol and 2.5% lard over a 3-month period. Plasma cholesterol and triacylglycerols increased on average 18.7- and 13.9-fold respectively, while erythrocyte membrane cholesterol content decreased 18% and total phospholipids by 54%. After 3 months of lipid hyperalimentation, 22% of the aortic arch was covered with large, early-stage, raised atheroma. Basal and calmodulin-activated (Ca2+ + Mg2+)-ATPase activities in erythrocyte membranes increased by 31% and 123%, respectively at 2 months, with a concomitant increase in calmodulin affinity (Km) from 15.6 to 4.2 nM. These differences were transient on account of changes in the control animals which exhibited a slowly developing sensitivity to calmodulin during maturation. Basal Ca2+ transport and passive Ca2+ permeability increased about 7-fold during the hyperlipidemic phase. This suggests that overt hyperlipidemia, leading to atherosclerotic plaque development, alters plasma membrane Ca2+ regulatory mechanisms including passive Ca2+ permeability. The changes in enzymatic function, membrane composition, and Ca2+ permeability seen in this red cell model system may be a reflection of early changes in cells that are directly involved in the development of atherosclerotic plaques.
细胞内游离钙活性部分由钙调蛋白调节的质膜钙泵决定。由于钙通透性的变化与动脉粥样硬化斑块形成有关，我们启动了一项脂质过度营养方案，在此期间我们测量了各种红细胞钙通量参数和早期动脉粥样硬化发展情况。在3个月的时间里，给青春期新西兰白兔喂食含0.5%胆固醇和2.5%猪油的饮食。血浆胆固醇和三酰甘油平均分别增加了18.7倍和13.9倍，而红细胞膜胆固醇含量下降了18%，总磷脂下降了54%。脂质过度营养3个月后，主动脉弓的22%被大的、早期的、隆起的动脉粥样硬化斑块覆盖。红细胞膜中的基础和钙调蛋白激活的（Ca2+ + Mg2+）-ATP酶活性在2个月时分别增加了31%和123%，同时钙调蛋白亲和力（Km）从15.6 nM增加到4.2 nM。由于对照动物的变化，这些差异是短暂的，对照动物在成熟过程中对钙调蛋白表现出逐渐发展的敏感性。在高脂血症阶段，基础钙转运和被动钙通透性增加了约7倍。这表明导致动脉粥样硬化斑块发展的明显高脂血症会改变质膜钙调节机制，包括被动钙通透性。在这个红细胞模型系统中看到的酶功能、膜组成和钙通透性的变化可能反映了直接参与动脉粥样硬化斑块发展的细胞的早期变化。
