Kitajima Shuji, Jin Yingji, Koike Tomonari, Yu Ying, Liu Enqi, Shiomi Masashi, Marcovina Santica M, Morimoto Masatoshi, Watanabe Teruo, Fan Jianglin
Analytical Research Center for Experimental Sciences, Saga University, Saga 849-8501, Japan.
Atherosclerosis. 2007 Aug;193(2):269-76. doi: 10.1016/j.atherosclerosis.2006.08.056. Epub 2006 Oct 11.
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.
血浆中低密度脂蛋白（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，尚不清楚Lp(a)是否会增强LDL对冠状动脉粥样硬化和心肌梗死的致动脉粥样硬化作用。为解决这一问题，我们将人Lp(a)转基因（Tg）兔与渡边遗传性高脂血症（WHHL）兔进行杂交，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兔的血浆总胆固醇、甘油三酯或高密度脂蛋白胆固醇（HDL-C）无显著变化。然而，Tg WHHL兔右冠状动脉的病变明显更大（p<0.05）。免疫组织化学染色显示，Tg WHHL兔的病变中细胞外基质成分丰富，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增加也与慢性缺血和心肌梗死的更高发生率相关。这些结果表明，在高胆固醇血症背景下，血浆Lp(a)水平升高会加重冠状动脉粥样硬化和心肌梗死。
