Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin
Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin
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DOI：
10.1096/fj.05-4857fje
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发表时间：
2006-01-01
期刊：
影响因子：
4.8
通讯作者：
Chavakis, T
中科院分区：
文献类型：
--
作者：
Sotiriou, SN;Orlova, VV;Chavakis, T
脂蛋白（a）[Lp（a）]由LDL和独特的载脂蛋白（a）[apo（a）]组成，含有类似纤溶酶原kringle 4的多个重复序列，被认为是动脉粥样硬化疾病发展的风险因素。然而，Lp（a）致动脉粥样硬化的潜在机制尚未完全了解。在这里，我们定义了一个新的功能，脂蛋白（a）在促进炎症细胞的招聘，可能有助于其致动脉粥样硬化。Lp（a）通过其apo（a）部分与β 2-整联蛋白Mac-1特异性相互作用，从而以Mac-1依赖性方式促进单核细胞的粘附及其跨内皮迁移。有趣的是，Mac-1和Lp（a）之间的相互作用在促动脉粥样硬化同型半胱氨酸的存在下得到加强，并被纤溶酶原/血管抑素kringle 4阻断。通过与Mac-1的相互作用，Lp（a）诱导了促炎转录因子NF κ B的活化，以及NF κ B相关的血栓前组织因子的表达。在动脉粥样硬化的冠状动脉中，发现Lp（a）定位于浸润的单核细胞上的Mac-1附近。综上所述，我们的数据表明，Lp（a），通过其载脂蛋白（a）部分，是β 2-整联蛋白Mac-1的配体，从而促进炎症细胞募集到动脉粥样硬化斑块。这些观察结果提示Lp（a）致动脉粥样硬化特性的新机制。
Lipoprotein(a) [Lp(a)], consisting of LDL and the unique constituent apolipoprotein(a) [apo(a)], which contains multiple repeats resembling plasminogen kringle 4, is considered a risk factor for the development of atherosclerotic disorders. However, the underlying mechanisms for the atherogenicity of Lp(a) are not completely understood. Here, we define a novel function of Lp(a) in promoting inflammatory cell recruitment that may contribute to its atherogenicity. Through its apo(a) moiety Lp(a) specifically interacts with the beta 2-integrin Mac-1, thereby promoting the adhesion of monocytes and their transendothelial migration in a Mac-1-dependent manner. Interestingly, the interaction between Mac-1 and Lp(a) was strengthened in the presence of proatherogenic homocysteine and was blocked by plasminogen/angiostatin kringle 4. Through its interaction with Mac-1, Lp(a) induced activation of the proinflammatory transcription factor NF kappa B, as well as the NF kappa B-related expression of prothrombotic tissue factor. In atherosclerotic coronary arteries Lp(a) was found to be localized in close proximity to Mac-1 on infiltrating mononuclear cells. Taken together, our data demonstrate that Lp(a), via its apo(a) moiety, is a ligand for the beta 2-integrin Mac-1, thereby facilitating inflammatory cell recruitment to atherosclerotic plaques. These observations suggest a novel mechanism for the atherogenic properties of Lp(a).