title: Elevated Expression of Matrix Metalloproteinase-9 not Matrix Metalloproteinase-2 Contributes to Progression of Extracranial Arteriovenous Malformation.
abstract: Extracranial arteriovenous malformations (AVMs) are rare but dangerous congenital lesions arising from direct arterial-venous shunts without intervening capillaries. Progressive infiltration, expansion, and soft tissue destruction lead to bleeding, pain, debilitation and disfigurement. The pathophysiology of AVMs is not well understood. Matrix Metalloproteinases (MMPs) are thought to play an important role in pathologic processes underlying many diseases. This study investigates the expression of MMP-9 and MMP-2 in aggressive extracranial AVMs. The differential expression of MMP-9 and its regulatory factors is also examined. Herein we demonstrate that mRNA and protein expressions of MMP-9, but not MMP-2, are significantly higher in AVM tissues compared to normal tissues. The serum level of MMP-9, but not MMP-2, is also elevated in AVM patients compared to healthy controls. MMP-9/neutrophil gelatinase-associated lipocalin (NGAL) complex is also significantly increased in AVM tissues. The MMP-9/ tissue inhibitor of metalloproteases-1 (TIMP-1) complex presents as a major form detected in normal tissues. The increased and aberrant expression of MMP-9 and specific MMP-9 forms may help explain the constitutive vascular remodeling and infiltrative nature of these lesions. Specific MMP-9 inhibitors would be a promising treatment for AVMs.
authors.affiliation: Center for Investigation of Congenital Anomalies of Vascular Development, Arkansas Vascular Biology Program, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Wei
authors.affiliation: Center for Investigation of Congenital Anomalies of Vascular Development, Arkansas Vascular Biology Program, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Haihong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Neslihan
authors.initials: N
authors.lastname: Cetin
authors.affiliation: University of Arkansas, Fayetteville, AR, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Miller
authors.affiliation: University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Teri
authors.initials: T
authors.lastname: Moak
authors.affiliation: Center for Investigation of Congenital Anomalies of Vascular Development, Arkansas Vascular Biology Program, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, AR, USA.|Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: James Y
authors.initials: JY
authors.lastname: Suen
authors.affiliation: Center for Investigation of Congenital Anomalies of Vascular Development, Arkansas Vascular Biology Program, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, AR, USA.|Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA.|Division of Pediatric Otolaryngology, Arkansas Children's Hospital, Little Rock, AR, USA.
authors.forename: Gresham T
authors.initials: GT
authors.lastname: Richter
mesh_terms: D001165:Arteriovenous Malformations / Q000473:pathology* / Q000503:physiopathology*; D020869:Gene Expression Profiling; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000096:biosynthesis*; D044967:Serum / Q000737:chemistry
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9