Lou X J, Boonmark N W, Horrigan F T, Degen J L, Lawn R M
Falk Cardiovascular Research Center, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12591-5. doi: 10.1073/pnas.95.21.12591.
To test directly whether fibrin(ogen) is a key binding site for apolipoprotein(a) [apo(a)] in vessel walls, apo(a) transgenic mice and fibrinogen knockout mice were crossed to generate fibrin(ogen)-deficient apo(a) transgenic mice and control mice. In the vessel wall of apo(a) transgenic mice, fibrin(ogen) deposition was found to be essentially colocalized with focal apo(a) deposition and fatty-streak type atherosclerotic lesions. Fibrinogen deficiency in apo(a) transgenic mice decreased the average accumulation of apo(a) in vessel walls by 78% and the average lesion (fatty streak type) development by 81%. Fibrinogen deficiency in wild-type mice did not significantly reduce lesion development. Our results suggest that fibrin(ogen) provides one of the major sites to which apo(a) binds to the vessel wall and participates in the generation of atherosclerosis.
为了直接测试纤维蛋白（原）是否是载脂蛋白(a)[apo(a)]在血管壁中的关键结合位点，将apo(a)转基因小鼠和纤维蛋白原敲除小鼠进行杂交，以产生缺乏纤维蛋白（原）的apo(a)转基因小鼠和对照小鼠。在apo(a)转基因小鼠的血管壁中，发现纤维蛋白（原）沉积与局灶性apo(a)沉积和脂肪条纹型动脉粥样硬化病变基本共定位。apo(a)转基因小鼠中纤维蛋白原缺乏使血管壁中apo(a)的平均积累减少78%，平均病变（脂肪条纹型）发展减少81%。野生型小鼠中纤维蛋白原缺乏并未显著降低病变发展。我们的结果表明，纤维蛋白（原）是apo(a)与血管壁结合的主要位点之一，并参与动脉粥样硬化的形成。
