Kramsch D M, Aspen A J, Apstein C S
J Clin Invest. 1980 May;65(5):967-81. doi: 10.1172/JCI109783.
Agents inhibiting calcium deposition into arteries are known to suppress atherosclerosis in animals. However, the precise role of calcium in atherogenesis is unknown. In this study, the specific Ca2+-antagonist lanthanum was used to attempt suppression of experimental atherosclerosis and to gain more insight into the possible effects of calcium on atherogenesis. Rabbits were fed an atherogenic diet with and without increasing doses of LaCl3. All cholesterol-fed rabbits showed marked increases in serum cholesterol and ca2+. Untreated atherogenic animals revealed pronounced gross and microscopic atherosclerosis and striking increases in the aortic content of cholesterol, collagen, "elastin," and calcium as well as of elastin calcium, polar amino acids, and cholesterol. With increasing LaCl3 dosage these abnormalities progressively decreased and were completely abolished at the highest dose. The ingested La3+ was absorbed only in small quantities and had no discernible effect on the calcium and connective tissue content of bone, skin, lung, heart, and skeletal muscle nor on myocardial function (left ventricle pressure and left ventricle dp/dt) or myocardial and muscle content in ATP and creatine phosphate. The data suggest that shifts in arterial Ca2+-distribution may play a decisive part in atherogenesis, and provision of arterial calcium homeostasis by La3+ a pivotal role in its prevention, despite hypercholesteremia. Other inhibitors of calcium deposition into arteries may exert their protective effect by similar mechanisms. However, a direct inhibition of atherogenesis by La3+ cannot entirely be ruled out in this study, although no direct effects of La3+ on tissue metabolism have as yet been reported.
已知抑制钙在动脉中沉积的药物可抑制动物的动脉粥样硬化。然而，钙在动脉粥样硬化形成中的具体作用尚不清楚。在本研究中，使用特定的钙离子拮抗剂镧来尝试抑制实验性动脉粥样硬化，并更深入地了解钙对动脉粥样硬化形成可能产生的影响。给兔子喂食致动脉粥样硬化饮食，同时添加不同剂量的LaCl3和不添加LaCl3。所有喂食胆固醇的兔子血清胆固醇和钙离子均显著升高。未经治疗的致动脉粥样硬化动物出现明显的大体和显微镜下动脉粥样硬化，主动脉中胆固醇、胶原蛋白、“弹性蛋白”、钙以及弹性蛋白钙、极性氨基酸和胆固醇的含量显著增加。随着LaCl3剂量的增加，这些异常逐渐减少，在最高剂量时完全消失。摄入的La3+仅少量被吸收，对骨骼、皮肤、肺、心脏和骨骼肌的钙和结缔组织含量以及心肌功能（左心室压力和左心室dp/dt）或心肌和肌肉中ATP和磷酸肌酸的含量均无明显影响。数据表明，动脉钙离子分布的改变可能在动脉粥样硬化形成中起决定性作用，尽管存在高胆固醇血症，但La3+维持动脉钙稳态在预防动脉粥样硬化中起关键作用。其他抑制钙在动脉中沉积的药物可能通过类似机制发挥其保护作用。然而，尽管尚未报道La3+对组织代谢有直接影响，但在本研究中不能完全排除La3+对动脉粥样硬化形成的直接抑制作用。
