BACKGROUND Atherosclerosis is an inflammatory process involving activation of monocytes recruited by various chemoattractant factors, among which lipoprotein(a) and its specific apolipoprotein apo(a). Lp(a) contains a specific apolipoprotein apo(a) which size is determined by a variable number of repeats of a specific structural domain, the kringle IV type 2 (IV-2). Lp(a) plasma concentration and apo(a) size is inversely correlated, and smaller apo(a) are major risk factors for coronary heart disease. DESIGN AND METHODS The aim of this study was to evaluate the effect of recombinant apo(a) isoforms (containing 10, 18 or 34 kringles) on monocytes interacting with type I collagen. RESULTS Apo(a) isoforms stimulated reactive oxygen species (ROS) and matrix metalloproteinase-9 (MMP-9) production by monocytes, and not modified monocytes adhesion on type I collagen. This effect was specific of apo(a) since no effect was observed in the presence of plasminogen and was inversely related to apo(a) size. The lysine analogue 6-aminohexanoic acid which blocks the lysine binding sites (LBS), and carboxypeptidase B (CpB) which cleaves carboxy-terminal lysine residues, abolished apo(a)-induced ROS and MMP-9 production, highlighting an effect mediated by apo(a) lysing-binding sites. CONCLUSIONS These results indicate that activation of collagen-primed monocytes stimulated with apo(a) is a Kringle number-dependent effect and reinforce the hypothesis of a role for small size apo(a) isoforms in atherothrombosis.

中文翻译：

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小尺寸载脂蛋白（a）亚型可增强胶原蛋白引发的单核细胞的炎症和蛋白水解潜能。

背景技术动脉粥样硬化是一种炎性过程，其涉及由多种化学吸引因子（包括脂蛋白（a）及其特异性载脂蛋白apo（a））募集的单核细胞的激活。Lp（a）包含特定的载脂蛋白apo（a），其大小由特定结构域（kringle IV 2型（IV-2））的可变重复数决定。Lp（a）血浆浓度与apo（a）大小呈负相关，较小的apo（a）是冠心病的主要危险因素。设计与方法这项研究的目的是评估重组apo（a）亚型（包含10、18或34个环）对与I型胶原相互作用的单核细胞的作用。结果Apo（a）亚型刺激单核细胞产生活性氧（ROS）和基质金属蛋白酶9（MMP-9），而不修饰单核细胞在I型胶原蛋白上的粘附力。该作用是apo（a）特有的，因为在纤溶酶原存在下未观察到作用，并且与apo（a）大小成反比。赖氨酸类似物6-氨基己酸可阻断赖氨酸结合位点（LBS），而羧肽酶B（CpB）则可切割羧基末端赖氨酸残基，从而消除了apo（a）诱导的ROS和MMP-9的产生，从而突出了由Apo（a）介导的作用apo（a）裂解结合位点。结论这些结果表明，由apo（a）刺激的胶原致敏单核细胞的激活是Kringle数依赖性效应，并增强了关于小apo（a）亚型在动脉粥样硬化中作用的假设。赖氨酸类似物6-氨基己酸可阻断赖氨酸结合位点（LBS），而羧肽酶B（CpB）则可切割羧基末端赖氨酸残基，从而消除了apo（a）诱导的ROS和MMP-9的产生，从而突出了由Apo（a）介导的作用apo（a）裂解结合位点。结论这些结果表明，由apo（a）刺激的胶原致敏单核细胞的激活是Kringle数依赖性效应，并增强了关于小apo（a）亚型在动脉粥样硬化中作用的假设。赖氨酸类似物6-氨基己酸可阻断赖氨酸结合位点（LBS），而羧肽酶B（CpB）则可切割羧基末端赖氨酸残基，从而消除了apo（a）诱导的ROS和MMP-9的产生，从而突出了由Apo（a）介导的作用apo（a）裂解结合位点。结论这些结果表明，由apo（a）刺激的胶原致敏单核细胞的激活是Kringle数依赖性效应，并增强了关于小apo（a）亚型在动脉粥样硬化中作用的假设。