Lysyl oxidase and endothelial dysfunction: mechanisms of lysyl oxidase down-regulation by pro-inflammatory cytokines
Lysyl oxidase and endothelial dysfunction: mechanisms of lysyl oxidase down-regulation by pro-inflammatory cytokines
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DOI：
10.2741/2879
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发表时间：
2008-01-01
影响因子：
3.1
通讯作者：
Rodriguez, Cristina
中科院分区：
文献类型：
--
作者：
Alcudia, Javier F.;Martinez-Gonzalez, Jose;Rodriguez, Cristina
赖氨酸氧化酶（LOX）在细胞外基质（ECM）成熟过程中起着关键作用。此外，LOX还具有细胞分化、迁移、转化和基因表达调控等新的生物学功能。在这种情况下，有人认为LOX表达异常可能是包括心血管疾病在内的多种病理过程发展的基础。LOX似乎在维持内皮屏障功能中起着至关重要的作用。事实上，越来越多的证据表明，这种酶在动脉粥样硬化危险因素和促炎细胞因子引发的动脉粥样硬化和内皮功能障碍中起作用。事实上，细胞因子如肿瘤坏死因子- α (tnf - α)调节血管LOX的表达。该细胞因子通过涉及TNF受体-2和蛋白激酶C激活的转录机制降低内皮细胞中LOX的表达和活性。有趣的是，体内研究显示tnf - α导致血管LOX表达下调。因此，LOX下调似乎与多种病理因素引起的内皮功能障碍有关。在心血管疾病治疗策略的发展中，LOX作为一个有希望的靶基因而上升。
Lysyl oxidase (LOX) plays a pivotal role in extracellular matrix (ECM) maturation. Furthermore, novel biological functions has been ascribed to LOX, among them cell differentiation, migration, transformation and regulation of gene expression. In this context, it has been suggested that abnormalities of LOX expression could underlie the development of multiple pathological processes including cardiovascular diseases. LOX seems to be crucial in the preservation of endothelial barrier function. In fact, accumulating evidences suggest a role of this enzyme in atherogenesis and endothelial dysfunction triggered by atherosclerotic risk factors and proinflammatory cytokines. Indeed, cytokines such as tumour necrosis factor-alpha (TNF-alpha) modulate vascular LOX expression. This cytokine decreases LOX expression and activity in endothelial cells through a transcriptional mechanism that involves TNF receptor-2 and protein kinase C activation. Interestingly, in vivo studies reveal that TNF-alpha causes a down-regulation of vascular LOX expression. Thus, LOX down-regulation seems to be associated to the endothelial dysfunction elicited by multiple pathological factors. LOX rises as a promising target gene for the development of therapeutic strategies in the treatment of cardiovascular diseases.