Study on the role of Lp (a) as an acute phase reactant and on the effects on arterial endothelial and smooth muscle cells.

尽管我们已经报道了急性心肌梗死和外科手术后血浆脂蛋白(a) [Lp (a)]的短暂增加，但这些增加的意义尚不清楚。本研究的目的是阐明Lp (a)在组织修复中的生理作用。免疫组织化学技术检查了许多炎症组织样本。肉芽组织的免疫组织化学特征随伤口愈合的不同阶段而不同。在第一阶段，抗载脂蛋白(a)和载脂蛋白B的免疫反应较弱且局部，而抗纤溶酶原和纤维蛋白原的免疫反应较强且广泛分布于组织表面。在第二阶段，肉芽组织被松散的纤维结缔组织覆盖，在靠近表面的地方观察到Lp (a)的明显阳性染色，表明Lp (a)可能阻止外部纤维蛋白溶解。Lp (a)也见于内皮细胞和纤维结缔组织下小血管的细胞外间隙。组织。在愈合的最后阶段，载脂蛋白(a)和载脂蛋白B在完全组织组织中检测不到。提示Lp (a)在创面愈合中起一定作用。在人脐静脉内皮细胞（HUVEC）体外实验中，观察了Lp (a)对内皮细胞迁移和增殖的刺激作用。这些效果不受其同工异构体的影响。在Lp (a)处理的培养液中加入抗bfgf，抑制Lp (a)诱导的HUVEC的迁移和增殖，但抑制不完全。百日咳毒素阻断bFGF的活性，也抑制Lp (a)诱导的HUVEC迁移。提示Lp (a)刺激bfgf介导的HUVEC迁移和增殖，可能促进血管生成。

Although we have reported transient increases of plasma lipoprotein (a) [Lp (a)] after acute myocardial infarction and surgical operations, the significance of these increases remains unclear. The purpose of the present study was to clarify the physiological roles of Lp (a) in tissue repair.Many samples from inflamed tissues were examined by immunohistochemical techniques. The immunohistochemical features of granulation tissues were characterized by different stages of wound healing. In the first stage, immunoreactivities for anti-apo (a) and-apo B were weak and focal, whereas those for anti-plasminogen and-fibrinogen were strong and widespead on the tissue surface. In the second stage, granulation tissue were covered with loose fibrous connective tissue, and markedly positive staining for Lp (a) was observed closer to the surface, suggesting that Lp (a) may prevent external fibrinolysis. Lp (a) was also found in endothelial cells and the extracellular space of small vessels underlying the fibrous connective. tissues. In the last stage of healing, apo (a) and apo B were not detectable in completely organized tissues. These findings suggest that Lp (a) plays a role in the wound healing.In in vitro study with human umbilical vein endothelial cell (HUVEC), the stimulatory effects of Lp (a) on the migration and proliferation of endothelial cells were observed. These effects were not affected with its isoforms. Anti-bFGF,added in the incubation medium treated with Lp (a), suppressed the Lp (a)-induced HUVEC migrations and proliferations, but the inhibitions were not complete. Pertussis toxin, that blocks the activity of bFGF,also suppressed Lp (a)-induced HUVEC migration. These findings suggest that Lp (a) stimulates the bFGF-mediated HUVEC migration and proliferation, and may promote the angiogenesis.