Suzuki Hideo, Kobayashi Hideyuki, Sato Fumiyasu, Yonemitsu Yoshikazu, Nakashima Yutaka, Sueishi Katsuo
Tokyo New Drug Research Laboratories I, Pharmaceutical Division, Kowa Co. Ltd, 2-17-43 Noguchi-cho, Higashi-murayama, Tokyo 189-0022, Japan.
J Atheroscler Thromb. 2003;10(2):109-16. doi: 10.5551/jat.10.109.
This study investigated the effect of pitavastatin, a 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitor with strong cholesterol-lowering activity, on the composition of atherosclerotic plaque. Pitavastatin ( 0.5mg/kg ) was administered to Watanabe heritable hyperlipidemic ( WHHL ) rabbits for 16 weeks, with the result that plasma total cholesterol ( TC ), very low density lipoprotein ( VLDL )-C, intermediate density lipoprotein ( IDL )-C and low density lipoprotein ( LDL )-C decreased by 28.6, 60.0, 42.3 and 21.7%, respectively. In the aorta, pitavastatin reduced the area of the lesion by 38.6%. In the pitavastatin group, the macrophage-positive area in the aortic plaque was reduced by 39.4%, and the areas occupied by collagen and a-smooth muscle actin ( alpha-SMA )-positive area increased by 66.4 and 91.7%, respectively. In the aortic arch, pitavastatin increased the average thickness of alpha-SMA in the plaque by 96.7% and reduced the vulnerability index by 76.0%. Furthermore, pitavastatin reduced the positive areas of monocyte chemoattractant protein ( MCP )-1, matrix metalloproteinase ( MMP )-3 and MMP-9 by 39.1, 40.6 and 52.3%, respectively. These results indicated that pitavastatin had an excellent lipid-lowering effect in WHHL rabbits, suppressing the progression of atherosclerosis and stabilizing atherosclerotic plaque.
本研究调查了匹伐他汀（一种具有强大降胆固醇活性的3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂）对动脉粥样硬化斑块成分的影响。将匹伐他汀（0.5mg/kg）给予渡边遗传性高脂血症（WHHL）兔16周，结果血浆总胆固醇（TC）、极低密度脂蛋白（VLDL）-C、中间密度脂蛋白（IDL）-C和低密度脂蛋白（LDL）-C分别降低了28.6%、60.0%、42.3%和21.7%。在主动脉中，匹伐他汀使病变面积减少了38.6%。在匹伐他汀组中，主动脉斑块中的巨噬细胞阳性面积减少了39.4%，胶原蛋白和α-平滑肌肌动蛋白（α-SMA）阳性区域所占面积分别增加了66.4%和91.7%。在主动脉弓中，匹伐他汀使斑块中α-SMA的平均厚度增加了96.7%，并使易损性指数降低了76.0%。此外，匹伐他汀使单核细胞趋化蛋白（MCP）-1、基质金属蛋白酶（MMP）-3和MMP-9的阳性区域分别减少了39.1%、40.6%和52.3%。这些结果表明，匹伐他汀在WHHL兔中具有优异的降脂作用，可抑制动脉粥样硬化的进展并稳定动脉粥样硬化斑块。
