Wiklund O, Bondjers G, Wright I, Camejo G
Department of Heart and Lung Disease, University of Göteborg, Sweden.
Atherosclerosis. 1996 Jan 5;119(1):57-67. doi: 10.1016/0021-9150(95)05628-9.
Lipoprotein deposition and increased intimal proteoglycans are characteristics of the atherosclerotic lesion in which low density lipoproteins (LDL) bind with high affinity to proteoglycans. The affinity of LDL to proteoglycans is dependent on its structural and compositional characteristics. This study investigated the relationship between serum lipid levels and LDL-proteoglycan reactivity. We also analyzed how lipid-lowering drugs affect this interaction. Patients with moderate hypercholesterolemia (n = 147) were randomized to pravastatin 40 mg o.d., gemfibrozil 600 mg b.i.d., gemfibrozil+pravastatin (same doses) or placebo. LDL reactivity with proteoglycans was analyzed by precipitation of serum with isolated human arterial proteoglycans. Reactivity was determined as amount of precipitated cholesterol or apolipoprotein (apo) B. Under the conditions used, 53% of the LDL cholesterol and 29% of serum apo B were precipitated. There were strong correlations between precipitated LDL and serum levels of cholesterol, LDL or apo B. No correlations were found with serum lipoprotein(a) (Lp(a)) levels. During pravastatin treatment, cholesterol was reduced by 26.5% and triglycerides by 9.8%. During gemfibrozil treatment corresponding figures were 16.8 and 40.2, and for the combined treatment, 27.5% and 34.2%. On all treatments, the reactivity of LDL with proteoglycan was reduced. The effects were significantly larger in the groups treated with gemfibrozil. This was correlated with the increase in high density lipoprotein (HDL) during gemfibrozil treatment. In hypercholesterolemia, the reactivity of LDL with proteoglycan is increased; treatment with lipid-lowering drugs lowers this reactivity, the effect being greatest for gemfibrozil. This might be due to conformational changes of LDL during treatment with gemfibrozil, unrelated to its lipid lowering effect. Since binding of LDL to proteoglycans is central in atherogenesis, this may be of importance for the role of gemfibrozil as an antiatherogenic drug.
脂蛋白沉积和内膜蛋白聚糖增加是动脉粥样硬化病变的特征，其中低密度脂蛋白（LDL）与蛋白聚糖具有高亲和力结合。LDL与蛋白聚糖的亲和力取决于其结构和组成特征。本研究调查了血脂水平与LDL-蛋白聚糖反应性之间的关系。我们还分析了降脂药物如何影响这种相互作用。将中度高胆固醇血症患者（n = 147）随机分为普伐他汀40mg每日一次、吉非贝齐600mg每日两次、吉非贝齐+普伐他汀（相同剂量）或安慰剂组。通过用分离的人动脉蛋白聚糖沉淀血清来分析LDL与蛋白聚糖的反应性。反应性以沉淀胆固醇或载脂蛋白（apo）B的量来确定。在所使用的条件下，53%的LDL胆固醇和29%的血清apo B被沉淀。沉淀的LDL与血清胆固醇、LDL或apo B水平之间存在强相关性。未发现与血清脂蛋白（a）（Lp（a））水平相关。在普伐他汀治疗期间，胆固醇降低了26.5%，甘油三酯降低了9.8%。在吉非贝齐治疗期间，相应的数字分别为16.8和40.2，联合治疗时为27.5%和34.2%。在所有治疗中，LDL与蛋白聚糖的反应性均降低。在吉非贝齐治疗组中，这种作用明显更大。这与吉非贝齐治疗期间高密度脂蛋白（HDL）的增加相关。在高胆固醇血症中，LDL与蛋白聚糖的反应性增加；降脂药物治疗可降低这种反应性，对吉非贝齐的效果最大。这可能是由于吉非贝齐治疗期间LDL的构象变化，与其降脂作用无关。由于LDL与蛋白聚糖的结合在动脉粥样硬化形成中起核心作用，这可能对吉非贝齐作为抗动脉粥样硬化药物的作用具有重要意义。
