Lp(a) enhances coronary atherosclerosis in transgenic Watanabe heritable hyperlipidemic rabbits
Lp(a) enhances coronary atherosclerosis in transgenic Watanabe heritable hyperlipidemic rabbits
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DOI：
10.1016/j.atherosclerosis.2006.08.056
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发表时间：
2007-08-01
期刊：
影响因子：
5.3
通讯作者：
Fan, Jianglin
中科院分区：
文献类型：
--
作者：
Kitajima, Shuji;Jin, Yingji;Fan, Jianglin
血浆 LDL 和脂蛋白 (a) [Lp(a)] 水平升高与动脉粥样硬化和冠心病风险增加相关。然而，Lp(a)是否会增强LDL对冠状动脉粥样硬化和心肌梗塞的致动脉粥样硬化作用尚不清楚。为了解决这个问题，我们将人类 Lp(a) 转基因 (Tg) 兔与渡边遗传性高脂血症 (WHHL) 兔杂交，并评估 Lp(a) 对冠状动脉粥样硬化发展的长期（2 岁时）影响。与非Tg WHHL 兔相比，Tg WHHL 兔血浆总胆固醇、甘油三酯或HDL-C 没有表现出显着变化。然而，Tg WHHL 兔子的右冠状动脉病变明显更大（p < 0.05）。免疫组化染色显示，Tg WHHL兔病灶内细胞外基质含量丰富，而细胞成分与非Tg WHHL兔无差异。 Tg WHHL 兔心脏冠状动脉粥样硬化的增加也与慢性缺血和心肌梗塞的较高发生率相关。这些结果表明，在高胆固醇血症的情况下，血浆 Lp(a) 水平升高会加剧冠状动脉粥样硬化和心肌梗塞。 (c) 2006 Elsevier Ireland Ltd. 保留所有权利。
Elevated plasma levels of LDL and lipoprotein (a) [Lp(a)] are associated with an increased risk of atherosclerosis and coronary heart disease. However, it is not known whether Lp(a) would enhance the atherogenic effect of LDL on coronary atherosclerosis and myocardial infarction. To address this issue, we cross-bred human Lp(a) transgenic (Tg) rabbits with Watanabe heritable hyperlipidemic (WHHL) rabbits and evaluated the long-term (at the age of 2 years) effects of Lp(a) on the development of coronary atherosclerosis. Compared to non-Tg WHHL rabbits, Tg WHHL rabbits did not show significant changes in plasma total cholesterol, triglycerides, or HDL-C. However, Tg WHHL rabbits showed significantly larger lesions in the right coronary arteries (p < 0.05). Immunohistochemical staining revealed that the lesions of Tg WHHL rabbits were enriched in the extracellular matrix contents whereas the cellular components were not different from those in non-Tg WHHL rabbits. Increased atherosclerosis in the coronary arteries in Tg WHHL rabbit hearts was also associated with a higher incidence of chronic ischemia and myocardial infarction. These results suggest that increased plasma levels of Lp(a) enhance coronary atherosclerosis and myocardial infarction in the setting of hypercholesterolemia. (c) 2006 Elsevier Ireland Ltd. All rights reserved.