Involvement of heparanase in atherosclerosis and other vessel wall pathologies.
Involvement of heparanase in atherosclerosis and other vessel wall pathologies.
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DOI：
10.1016/j.matbio.2013.03.002
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发表时间：
2013-06-24
期刊：
影响因子：
6.9
通讯作者：
Ilan, Neta
中科院分区：
文献类型：
--
作者：
Vlodavsky, Israel;Blich, Miry;Li, Jin-Ping;Sanderson, Ralph D.;Ilan, Neta
关键词：
乙酰肝素酶是哺乳动物中唯一的一种降解硫酸乙酰肝素的糖苷内切酶，与肿瘤转移、血管生成、炎症和肾功能障碍等密切相关。尽管硫酸乙酰肝素蛋白聚糖在血管生物学中广泛存在并产生影响，但乙酰肝素酶在血管壁疾病中的重要性被低估。血管是高度活跃的结构，其形态在改变的全身和局部条件下迅速适应以维持血管功能。在某些病理（再狭窄、血栓形成、动脉粥样硬化）中，这种通常有益的适应可能对整体功能有害。乙酰肝素酶对动脉结构力学和修复的酶依赖性和非酶依赖性作用密切调节血管内支架术后动脉顺应性和新生内膜增殖。此外，乙酰肝素酶促进血管损伤后的血栓形成，并在人颈动脉粥样硬化中促成促凝状态。重要的是，乙酰肝素酶与动脉粥样硬化斑块的发展和进展密切相关，包括稳定斑块向不稳定斑块的转变。因此，急性心肌梗死患者血浆中乙酰肝素酶水平显著升高。值得注意的是，乙酰肝素酶激活巨噬细胞，导致与斑块向易损性进展相关的细胞因子表达的显著诱导。总之，乙酰肝素酶作为易损病变发展的调节剂和动脉粥样硬化和相关血管壁并发症的治疗干预的潜在靶点而出现。
Heparanase, the sole mammalian endoglycosidase degrading heparan sulfate, is causally involved in cancer metastasis, angiogenesis, inflammation and kidney dysfunction. Despite the wide occurrence and impact of heparan sulfate proteoglycans in vascular biology, the significance of heparanase in vessel wall disorders is underestimated. Blood vessels are highly active structures whose morphology rapidly adapts to maintain vascular function under altered systemic and local conditions. In some pathologies (restenosis, thrombosis, atherosclerosis) this normally beneficial adaptation may be detrimental to overall function. Enzymatic dependent and independent effects of heparanase on arterial structure mechanics and repair closely regulate arterial compliance and neointimal proliferation following endovascular stenting. Additionally, heparanase promotes thrombosis after vascular injury and contributes to a pro-coagulant state in human carotid atherosclerosis. Importantly, heparanase is closely associated with development and progression of atherosclerotic plaques, including stable to unstable plaque transition. Consequently, heparanase levels are markedly increased in the plasma of patients with acute myocardial infarction. Noteworthy, heparanase activates macrophages, resulting in marked induction of cytokine expression associated with plaque progression towards vulnerability. Together, heparanase emerges as a regulator of vulnerable lesion development and potential target for therapeutic intervention in atherosclerosis and related vessel wall complications.
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