Cederholm Anna, Frostegård Johan
Department of Medicine, Karolinska University Hospital, Huddinge, Sweden.
Ann N Y Acad Sci. 2007 Jun;1108:96-103. doi: 10.1196/annals.1422.011.
During recent years it has become evident that atherosclerosis is an inflammatory disease. Furthermore, immune reactions and especially autoimmunity, were demonstrated to modulate atherosclerosis in animal experiments. An interesting example of how autoimmune reactions can influence atherosclerosis and consequences thereafter, is systemic lupus erythematosus (SLE)-associated cardiovascular disease (CVD). Antithrombotic effect exerted by Annexin A5 (ANXA5) is thought to be mediated mainly by forming a mechanical shield over phospholipids (PLs) reducing availability of PLs for coagulation reactions. However, more specific properties of ANXA5 might be of importance for its antithrombotic function. Such examples include downregulation of surface-expressed tissue factor (TF), as well as upregulation of urokinase-type plasminogen activator (uPA) by ANXA5. Also, interaction of ANXA5 with ligands involved in hemostasis, such as sulfatide and heparin, has been demonstrated. We have recently described a novel mechanism potentially contributing to atherothrombosis in SLE, with ANXA5 binding to endothelium decreased in SLE, an effect caused by antiphospholipid antibodies (aPL). It may be hypothesized that ANXA5 can be effective as a treatment to prevent plaque rupture and atherothrombosis not only in SLE, but also in the general population prone to CVD. Antiatherothrombotic potential of ANXA5 deserves further attention and careful studies as the mechanism behind the majority of clinically significant cardiovascular ischemic disease is atherothrombosis, formed on an underlying vulnerable atherosclerotic lesion. It may be hypothesized that ANXA5 can be effective as a treatment to prevent plaque rupture and atherothrombosis not only in SLE, but also in a general population prone to CVD.
近年来，动脉粥样硬化是一种炎症性疾病这一点已变得很明显。此外，在动物实验中已证明免疫反应尤其是自身免疫可调节动脉粥样硬化。自身免疫反应如何影响动脉粥样硬化及其后续后果的一个有趣例子是系统性红斑狼疮（SLE）相关的心血管疾病（CVD）。膜联蛋白A5（ANXA5）发挥的抗血栓作用被认为主要是通过在磷脂（PL）上形成机械屏障，减少PL用于凝血反应的可用性来介导的。然而，ANXA5的更特殊性质可能对其抗血栓功能很重要。这些例子包括下调表面表达的组织因子（TF），以及ANXA5上调尿激酶型纤溶酶原激活剂（uPA）。此外，还证明了ANXA5与参与止血的配体如硫苷脂和肝素的相互作用。我们最近描述了一种可能导致SLE中动脉粥样硬化血栓形成的新机制，在SLE中ANXA5与内皮的结合减少，这是由抗磷脂抗体（aPL）引起的一种效应。可以推测，ANXA5不仅在SLE中，而且在易患CVD的普通人群中，都可以作为预防斑块破裂和动脉粥样硬化血栓形成的有效治疗方法。由于大多数具有临床意义的心血管缺血性疾病背后的机制是在潜在易损动脉粥样硬化病变上形成的动脉粥样硬化血栓形成，ANXA5的抗动脉粥样硬化血栓形成潜力值得进一步关注和仔细研究。可以推测，ANXA5不仅在SLE中，而且在易患CVD的普通人群中，都可以作为预防斑块破裂和动脉粥样硬化血栓形成的有效治疗方法。
