Hyaluronan-mediated angiogenesis in vascular disease

Uncovering RHAMM and CD44 receptor signaling pathways

Mark Slevin, Jurek Krupinski, John Gaffney, Sabine Matou, David West, Horace Delisser, Rashmin C. Savani, Shant Kumar

Research output: Contribution to journalArticle

257 Citations (Scopus)

Abstract

The correct formation of new blood vessels from existing vasculature (angiogenesis) is essential for embryogenesis and the effective repair of damaged or wounded tissues. However, excessive and detrimental vascularization also occurs in neoplasia, promoting tumour growth and metastasis, as well as in proliferative diabetic retinopathy and atherosclerosis. Greater understanding of the mechanisms controlling the angiogenic process will allow optimization of wound healing, and provide mechanisms to inhibit vascularization in tumours and other diseases. Evidence supports a cascade of events in which the perturbation of one of the steps is sufficient to significantly inhibit neovascularization. The extracellular macromolecules, notably glycosaminoglycans (GAGs), are important mediators of angiogenesis. Hyaluronan (HA), a large, non-sulphated GAG, was first discovered in the vitreous of the eye [Meyer, K., Palmer, J.W. 1936. The polysaccharide of the vitreous humour. J. Biol. Chem. 107, 629-634.], and is ubiquitously expressed in the extracellular matrix (ECM) of tissues. Native high molecular weight HA (n-HA) is anti-angiogenic, whereas HA degradation products (o-HA; 3-10 disaccharides) stimulate endothelial cell (EC) proliferation, migration and tube formation following activation of specific HA receptors in particular, CD44 and Receptor for HA-Mediated Motility (RHAMM, CD168). The involvement of HA in the regulation of angiogenesis makes it an attractive therapeutic target. We review the role of o-HA in modulation of angiogenesis during tissue injury, and vascular disease, focusing on receptor-mediated signal transduction pathways that have been evaluated.

Original languageEnglish (US)
Pages (from-to)58-68
Number of pages11
JournalMatrix Biology
Volume26
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint

Hyaluronic Acid
Vascular Diseases
Glycosaminoglycans
Signal Transduction
CD44 Antigens
Vitreous Body
Neoplasms
Disaccharides
Diabetic Retinopathy
Wound Healing
Embryonic Development
Cell Movement
Extracellular Matrix
Polysaccharides
Blood Vessels
Atherosclerosis
Endothelial Cells
Molecular Weight
Cell Proliferation
Neoplasm Metastasis

Keywords

  • Angiogenesis
  • CD44
  • Hyaluronan
  • RHAMM
  • Signaling pathways

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Slevin, M., Krupinski, J., Gaffney, J., Matou, S., West, D., Delisser, H., ... Kumar, S. (2007). Hyaluronan-mediated angiogenesis in vascular disease: Uncovering RHAMM and CD44 receptor signaling pathways. Matrix Biology, 26(1), 58-68. https://doi.org/10.1016/j.matbio.2006.08.261

Hyaluronan-mediated angiogenesis in vascular disease : Uncovering RHAMM and CD44 receptor signaling pathways. / Slevin, Mark; Krupinski, Jurek; Gaffney, John; Matou, Sabine; West, David; Delisser, Horace; Savani, Rashmin C.; Kumar, Shant.

In: Matrix Biology, Vol. 26, No. 1, 01.2007, p. 58-68.

Research output: Contribution to journalArticle

Slevin, M, Krupinski, J, Gaffney, J, Matou, S, West, D, Delisser, H, Savani, RC & Kumar, S 2007, 'Hyaluronan-mediated angiogenesis in vascular disease: Uncovering RHAMM and CD44 receptor signaling pathways', Matrix Biology, vol. 26, no. 1, pp. 58-68. https://doi.org/10.1016/j.matbio.2006.08.261
Slevin, Mark ; Krupinski, Jurek ; Gaffney, John ; Matou, Sabine ; West, David ; Delisser, Horace ; Savani, Rashmin C. ; Kumar, Shant. / Hyaluronan-mediated angiogenesis in vascular disease : Uncovering RHAMM and CD44 receptor signaling pathways. In: Matrix Biology. 2007 ; Vol. 26, No. 1. pp. 58-68.
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