Premium
The Hyaluronan Receptor RHAMM Promotes Constrictive Artery Wall Remodeling
Author(s) -
Ma Xue,
Pearce Jeffrey D,
Li Jing,
Wilson David B.,
English William P.,
Edwards Matthew S.,
Geary Randolph L.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.870.3
Subject(s) - restenosis , extracellular matrix , hyaluronic acid , ligation , receptor , chemistry , neointima , microbiology and biotechnology , medicine , anatomy , biochemistry , biology , stent
Constrictive remodeling of the extracellular matrix (ECM) contributes significantly to restenosis after angioplasty. Hyaluronan (HA) accumulates at sites of injury where it facilitates collagen remodeling. SMCs interact with HA via specific receptor RHAMM for HA‐induced migration. We hypothesized that RHAMM may also mediate SMC‐ECM interactions that alter the extent of constrictive remodeling. We determined the role of RHAMM in HA‐induced SMC adhesion to collagen, migration, and collagen gel contraction by blocking cell‐surface RHAMM with antibodies or by employing SMC from RHAMM −/− (rKO) mice. We then studied the impact of RHAMM on constrictive remodeling by measuring changes in artery wall geometry 1 month after carotid ligation in rKO and RHAMM+/+ (rWT) mice. Attachment to collagen‐coated plates was enhanced by HA and inhibited by antibody blockade of RHAMM. RKO SMC also showed reduced adhesion. HA enhanced SMC contraction of collagen gels and RHAMM blockade or RHAMM gene deletion increased the extent of gel contraction even further. RHAMM also mediated constrictive artery wall remodeling in vivo , as carotid artery wall caliber was significantly greater in rKO mice after ligation. Neointimal thickening was similar but artery size (EEL area) was much larger in rKO mice. Thus, strategies to block RHAMM at sites of injury may prove useful in the prevention of clinical restenosis.