ArticleJournal of vascular surgery2014
Loss of the hyaluronan receptor RHAMM prevents constrictive artery wall remodeling.
Article in Journal of vascular surgery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- A Novel Role of Hyaluronan and Its Membrane Receptors, CD44 and RHAMM, in Obesity-Related Kidney Pathology.Biomolecules · 2025Article
- Elevated RHAMM as a biomarker for predicting diabetic kidney disease in patients with type 2 diabetes.Clinical kidney journal · 2024Article
- Cardiovascular Effects Mediated by HMMR and CD44.Mediators of inflammation · 2021Review
- The Receptor for Hyaluronan-Mediated Motility (CD168) promotes inflammation and fibrosis after acute lung injury.Matrix biology : journal of the International Society for Matrix Biology · 2019Article
- The hyaluronan-mediated motility receptor RHAMM promotes growth, invasiveness and dissemination of colorectal cancer.Oncotarget · 2017Article
- Scavenger receptor class A member 5 (SCARA5) and suprabasin (SBSN) are hub genes of coexpression network modules associated with peripheral vein graft patency.Journal of vascular surgery · 2016Article
- Deletion of Hyaluronan Synthase 3 Inhibits Neointimal Hyperplasia in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2016Article
- Hyaluronan as a therapeutic target in human diseases.Advanced drug delivery reviews · 2016Review
- Hyaluronan and RHAMM in wound repair and the "cancerization" of stromal tissues.BioMed research international · 2014Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectiveConstrictive extracellular matrix (ECM) remodeling contributes significantly to restenosis after arterial reconstruction, but its molecular regulation is poorly defined. Hyaluronan (HA) accumulates within ECM at sites of injury where it is thought to facilitate smooth muscle cell (SMC) trafficking and collagen remodeling analogous to its role in cutaneous wound healing. SMC receptors for HA include receptor for hyaluronan-mediated motility (RHAMM), which mediates HA-induced migration. We hypothesized RHAMM would also mediate SMC-matrix interactions to alter the extent of constrictive remodeling.
methodsWe studied the role of RHAMM in SMC attachment to collagen, migration, and contraction of collagen gels using blocking antibodies and SMC from RHAMM -/- knockout mice. We then determined the role of RHAMM in constrictive artery wall remodeling by comparing changes in wall geometry in RHAMM -/- vs wild-type (WT) RHAMM +/+ controls 1 month after carotid ligation.
resultsHA increased SMC attachment to collagen-coated plates, but blocking RHAMM reduced adhesion (P = .025). RHAMM -/- SMC also demonstrated reduced adhesion (% adherent: 36.1 ± 2.2 vs 76.3 ± 1.9; P < .05). SMC contraction of collagen gels was enhanced by HA and further increased by RHAMM blockade (P < .01) or knockout (gel diameter, mm: RHAMM -/-, 6.7 ± 0.1 vs WT 9.8 ± 0.1; P < .01). RHAMM promoted constrictive remodeling in vivo as carotid artery size was significantly larger in knockout mice 1 month after ligation. Neointimal thickening, however, was not affected in RHAMM -/- (P = NS vs WT), but lumen size was significantly larger (lumen area, μm(2): 52.4 ± 1.4 × 10(3) vs 10.4 ± 1.8 × 10(3); P = .01) because artery size constricted less (external elastic lamina area, μm(2): RHAMM -/-, 92.4 ± 4.7 × 10(3) vs WT, 51.3 ± 5.9 × 10(3); P = .015). Adventitial thickening and collagen deposition were also more extensive in ligated RHAMM -/- carotids (adventitial thickness, μm: 218 ± 12.2 vs 109 ± 7.9; P = .01).
conclusionsHA activation of RHAMM significantly impacts SMC-ECM adhesive interactions and contributes to constrictive artery wall remodeling in mice. Strategies to block RHAMM at sites of vessel injury may prove useful in the prevention of clinical restenosis.
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