title: Involvement of heparanase in atherosclerosis and other vessel wall pathologies.
abstract: 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.
authors.affiliation: Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion, Haifa, Israel. vlodavsk@cc.huji.ac.il
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
authors.forename: Miry
authors.initials: M
authors.lastname: Blich
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Li
authors.forename: Ralph D
authors.initials: RD
authors.lastname: Sanderson
authors.forename: Neta
authors.initials: N
authors.lastname: Ilan
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D002339:Carotid Arteries / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005966:Glucuronidase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D058226:Plaque, Atherosclerotic / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D013927:Thrombosis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D006497:Heparan Sulfate; D000099175:Heparanase