Williams J K, Sukhova G K, Herrington D M, Libby P
Department of Comparative Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1040, USA.
J Am Coll Cardiol. 1998 Mar 1;31(3):684-91. doi: 10.1016/s0735-1097(97)00537-8.
This study examined the direct effects of pravastatin on the artery wall of atherosclerotic monkeys after dietary lipid lowering.
Clinical trials suggest that hepatic hydroxymethylglutaryl coenzyme A reductase inhibitors may reduce the risk of coronary heart disease out of proportion to their effect on angiographically assessed lumen stenosis.
Thirty-two cynomolgus monkeys were fed an atherogenic diet for 2 years (progression phase) and then fed a lipid-lowering diet either containing (n = 14) or not containing (n = 18) pravastatin in the diet for an additional 2 years (treatment phase). As designed, total plasma cholesterol and high density lipoprotein concentrations did not differ between groups at the beginning of or during the treatment phase of the experiment (p > 0.05).
Quantitative angiography revealed that coronary arteries of the pravastatin-treated monkeys dilated 10 +/- 3%, whereas those from untreated control monkeys constricted -2 +/- 2% in response to acetylcholine (p < 0.05). There were no treatment effects on plaque size of coronary arteries measured at the end of the treatment phase of the study (0.110 +/- 0.048 mm2 [untreated] vs. 0.125 +/- 0.051 mm2 [pravastatin]; p > 0.05) or on the amount of reduction in plaque size in common iliac arteries during the treatment phase of the study (48 +/- 5% [untreated] vs. 45 +/- 6% [pravastatin]; p > 0.05). However, histochemical analysis of the atherosclerotic lesions indicated that the arteries from pravastatin-treated monkeys had significantly fewer macrophages in the intima and media, less calcification and less neovascularization in the intima (p < 0.05).
We conclude that compared with control monkeys, the arteries of pravastatin-treated monkeys had better dilator function and plaque characteristics more consistent with plaque stability than those of monkeys not receiving pravastatin. These beneficial arterial effects of pravastatin occurred independently of plasma lipoprotein concentrations and despite similar changes in plaque size between the groups.
本研究检测了普伐他汀在饮食降血脂后对动脉粥样硬化猴子动脉壁的直接作用。
临床试验表明，肝脏羟甲基戊二酰辅酶A还原酶抑制剂降低冠心病风险的作用与其对血管造影评估的管腔狭窄的作用不成比例。
32只食蟹猴先接受致动脉粥样硬化饮食2年（进展期），然后再接受含（n = 14）或不含（n = 18）普伐他汀的降脂饮食2年（治疗期）。按照设计，在实验治疗期开始时或期间，两组间的总血浆胆固醇和高密度脂蛋白浓度无差异（p > 0.05）。
定量血管造影显示，接受普伐他汀治疗的猴子的冠状动脉扩张了10±3%，而未治疗的对照猴子的冠状动脉对乙酰胆碱反应收缩了-2±2%（p < 0.05）。在研究治疗期结束时，对冠状动脉斑块大小（0.110±0.048 mm²[未治疗组] vs. 0.125±0.051 mm²[普伐他汀组]；p > 0.05）或在研究治疗期内髂总动脉斑块大小的减少量（48±5%[未治疗组] vs. 45±6%[普伐他汀组]；p > 0.05）均无治疗效果。然而，动脉粥样硬化病变的组织化学分析表明，接受普伐他汀治疗的猴子的动脉在内膜和中膜中的巨噬细胞明显减少，内膜中的钙化和新生血管形成也较少（p < 0.05）。
我们得出结论，与对照猴子相比，接受普伐他汀治疗的猴子的动脉具有更好的扩张功能，其斑块特征比未接受普伐他汀治疗的猴子的斑块更稳定。普伐他汀对动脉的这些有益作用独立于血浆脂蛋白浓度，尽管两组间斑块大小有相似变化。
