Document Detail


Heparanase alters arterial structure, mechanics, and repair following endovascular stenting in mice.
MedLine Citation:
PMID:  19096032     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Heparan sulfate proteoglycans (HSPGs) are potent regulators of vascular remodeling and repair. Heparanase is the major enzyme capable of degrading heparan sulfate in mammalian cells. Here we examined the role of heparanase in controlling arterial structure, mechanics, and remodeling. In vitro studies supported that heparanase expression in endothelial cells serves as a negative regulator of endothelial inhibition of vascular smooth muscle cell (vSMC) proliferation. Arterial structure and remodeling to injury were also modified by heparanase expression. Transgenic mice overexpressing heparanase had increased arterial thickness, cellular density, and mechanical compliance. Endovascular stenting studies in Zucker rats demonstrated increased heparanase expression in the neointima of obese, hyperlipidemic rats in comparison to lean rats. The extent of heparanase expression within the neointima strongly correlated with the neointimal thickness following injury. To test the effects of heparanase overexpression on arterial repair, we developed a novel murine model of stent injury using small diameter self-expanding stents. Using this model, we found that increased neointimal formation and macrophage recruitment occurs in transgenic mice overexpressing heparanase. Taken together, these results support a role for heparanase in the regulation of arterial structure, mechanics, and repair.
Authors:
Aaron B Baker; Adam Groothuis; Michael Jonas; David S Ettenson; Tarek Shazly; Eyal Zcharia; Israel Vlodavsky; Philip Seifert; Elazer R Edelman
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-12-18
Journal Detail:
Title:  Circulation research     Volume:  104     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-13     Completed Date:  2009-03-12     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  380-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Angioplasty
Animals
Aorta / pathology
Aortic Aneurysm / pathology,  physiopathology
Disease Models, Animal
Endothelium, Vascular / cytology,  injuries*
Feedback, Physiological / physiology
Gene Expression / physiology
Glucuronidase / genetics*,  metabolism*
Humans
Hyperlipidemias / pathology
Macrophages / pathology
Mice
Mice, Transgenic
Muscle, Smooth, Vascular / cytology,  injuries*
Obesity / pathology
Paracrine Communication / physiology
Rats
Rats, Zucker
Stents / adverse effects*
Tunica Intima / cytology,  injuries
Umbilical Cord / cytology
Grant Support
ID/Acronym/Agency:
R01 GM049039/GM/NIGMS NIH HHS; R01 HL067246/HL/NHLBI NIH HHS; R01 HL067246-01A2/HL/NHLBI NIH HHS; R01 HL67246/HL/NHLBI NIH HHS; R0I CA106456/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
EC 3.2.1.-/heparanase; EC 3.2.1.31/Glucuronidase
Comments/Corrections
Comment In:
Circ Res. 2009 Feb 13;104(3):277-9   [PMID:  19213960 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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