Hyaluronan and Angiogenesis: Molecular Mechanisms and Clinical Applications

Kumar, Shant; Ponting, J; Rooney, Paul; Kumar, Patricia; Pye, David; Wang, M.

doi:10.1007/978-1-4757-9188-4_24

Cited by 10 publications

(6 citation statements)

References 32 publications

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“…In particular, HA is a potent regulator of vascular endothelial cell (EC) function. Native high molecular weight HA is anti-angiogenic, inhibiting EC proliferation and migration (6 -8) as well as capillary formation in a three-dimensional collagen gel model (9), whereas degradation products of specific size (3-10 disaccharide units; o-HA) stimulate EC proliferation (10 -11), migration (12), sprout formation (13), and result in angiogenesis in the chick chorioallantoic membrane (14) and in myocardial infarction (15). Generation of this "angiogenic" o-HA from the naturally occurring HA polymer is mediated by the endoglycosidase hyaluronidase (16), in association with tissue damage, inflammatory disease, and in certain tumors (10,16,17).…”

mentioning

confidence: 99%

Angiogenic Oligosaccharides of Hyaluronan Induce Multiple Signaling Pathways Affecting Vascular Endothelial Cell Mitogenic and Wound Healing Responses

Slevin

Kumar

Gaffney

2002

Journal of Biological Chemistry

311

228

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Hyaluronan (HA) is a large nonsulfated glycosaminoglycan and an important regulator of angiogenesis, in particular, the growth and migration of vascular endothelial cells. We have identified some of the key intermediates responsible for induction of mitogenesis and wound recovery. Treatment of bovine aortic endothelial cells with oligosaccharides of hyaluronan (o-HA) resulted in rapid tyrosine phosphorylation and plasma membrane translocation of phospholipase C␥1 (PLC␥1). Cytoplasmic loading with inhibitory antibodies to PLC␥1, G␤, and G␣ i/o/t/z inhibited activation of extracellular-regulated kinase 1/2 (ERK1/2). Treatment with the G␣ i/o inhibitor, pertussis toxin, reduced o-HA-induced PLC␥1 tyrosine phosphorylation, protein kinase C (PKC) ␣ and ␤1/2 membrane translocation, ERK1/2 activation, mitogenesis, and wound recovery, suggesting a mechanism for o-HA-induced angiogenesis through Gproteins, PLC␥1, and PKC. In particular, we demonstrated a possible role for PKC␣ in mitogenesis and PKC␤1/2 in wound recovery. Using antisense oligonucleotides and the Ras farnesylation inhibitor FTI-277, we showed that o-HA-induced bovine aortic endothelial cell proliferation, wound recovery, and ERK1/2 activation were also partially dependent on Ras activation, and that o-HA-stimulated tyrosine phosphorylation of the adapter protein Shc, as well as its association with Sos1. Binding of Src to Shc was required for its activation and for Ras-dependent activation of ERK1/2, cell proliferation, and wound recovery. Neither Src nor Ras activation was inhibited by pertussis toxin, suggesting that their activation was independent of heterotrimeric G-proteins. However, the specific Src kinase inhibitor PP2 inhibited G␤ subunit co-precipitation with PLC␥1, suggesting a possible role for Src in activation of PLC␥1 and interaction between two distinct o-HA-induced signaling pathways.

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mentioning

confidence: 99%

Angiogenic Oligosaccharides of Hyaluronan Induce Multiple Signaling Pathways Affecting Vascular Endothelial Cell Mitogenic and Wound Healing Responses

Slevin

Kumar

Gaffney

2002

Journal of Biological Chemistry

311

228

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“…Notably, the high-molecular weight HA polymer (~107 kDa) is antiangiogenic and inhibits EC proliferation and migration, as well as capillary formation in collagen gels. In contrast, low-molecular weight degradation products (three to ten disaccharide units) stimulate EC proliferation, migration, and sprouting [201][202][203] and induce angiogenesis in the infarcted myocardium [204] and in the chick chorioallantoic membrane [205] . Generation of this "angiogenic" HA from naturally occurring HA is mediated by the endoglycosidase hyaluronidase (via polysaccharide degradation), by processes associated with tissue damage, inflammatory disease, and certain types of tumors [206] .…”

Section: Hyaluronic Acidmentioning

confidence: 95%

Stem Cells and Scaffolds for Vascularizing Engineered Tissue Constructs

Luong

Gerecht

2008

Engineering of Stem Cells

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The clinical impact of tissue engineering depends upon our ability to direct cells to form tissues with characteristic structural and mechanical properties from the molecular level up to organized tissue. Induction and creation of functional vascular networks has been one of the main goals of tissue engineering either in vitro, for the transplantation of prevascularized constructs, or in vivo, for cellular organization within the implantation site. In most cases, tissue engineering attempts to recapitulate certain aspects of normal development in order to stimulate cell differentiation and functional tissue assembly. The induction of tissue growth generally involves the use of biodegradable and bioactive materials designed, ideally, to provide a mechanical, physical, and biochemical template for tissue regeneration. Human embryonic stem cells (hESCs), derived from the inner cell mass of a developing blastocyst, are capable of differentiating into all cell types of the body. Specifically, hESCs have the capability to differentiate and form blood vessels de novo in a process called vasculogenesis. Human ESC-derived endothelial progenitor cells (EPCs) and endothelial cells have substantial potential for microvessel formation, in vitro and in vivo. Human adult EPCs are being isolated to understand the fundamental biology of how these cells are regulated as a population and to explore whether these cells can be differentiated and reimplanted as a cellular therapy in order to arrest or even reverse damaged vasculature. This chapter focuses on advances made toward the generation and engineering of functional vascular tissue, focusing on both the scaffolds - the synthetic and biopolymer materials - and the cell sources - hESCs and hEPCs.

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“…Hyaluronan is also an important regulator of angiogenesis and, specifically, growth and migration of vascular endothelial cells (22). Whereas native high molecular weight HA is anti-angiogenic, inhibiting endothelial cell proliferation and migration (23) as well as capillary formation (24), its degradation products (containing 3 – 10 disaccharide units) stimulate proliferation (25), migration, and sprout formation and result in angiogenesis after myocardial infarction (26). Hyaluronan is absorbed from the peritoneal cavity and readily metabolized.…”

Section: Hyaluronan (Ha)mentioning

confidence: 99%

Agents that Modulate Peritoneal Membrane Structure and Function

Díaz-Buxó

Gotloib

2007

Perit Dial Int

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Extensive experience with chronic peritoneal dialysis has identified a series of functional and anatomical pathologic changes in the peritoneal membrane thought to be the result of repeated insults from bioincompatible solutions. Laboratory and clinical findings from recent investigations often conflict and are difficult to interpret due to variations in methodologies, animal models, study designs, and data analyses. The principal pathophysiologic mechanisms identified thus far are oxidative stress, inflammation, and their consequences. Many substances used to neutralize the action of these insults, prevent formation of toxic compounds, or directly alter solute and water transport to improve peritoneal membrane performance have been studied. We herein review the most promising of these substances or those that deserve attention because their use has contributed to better understanding of peritoneal pathophysiology. Most peritoneal solution additives have proved useless due to their toxicity and undesirable effects, ineffectiveness, or manufacturing limitations. A few substances deserve more attention, particularly those capable of restoring negatively charged membrane sites, those that somehow improve permselectivity, scavengers of oxidants, and advanced glycation end-product inhibitors and breakers. Recent publications on clinical experience with neutral pH, low glucose degradation product (GDP) peritoneal solutions, although few and preliminary, are most encouraging. The virtual elimination of GDPs in these novel solutions will probably preclude the need for GDP scavengers and inhibitors. Nonetheless, there is room for further significant improvement in solution biocompatibility and for compounds that may restore peritoneal function.

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Hyaluronan and Angiogenesis: Molecular Mechanisms and Clinical Applications

Cited by 10 publications

References 32 publications

Angiogenic Oligosaccharides of Hyaluronan Induce Multiple Signaling Pathways Affecting Vascular Endothelial Cell Mitogenic and Wound Healing Responses

Angiogenic Oligosaccharides of Hyaluronan Induce Multiple Signaling Pathways Affecting Vascular Endothelial Cell Mitogenic and Wound Healing Responses

Stem Cells and Scaffolds for Vascularizing Engineered Tissue Constructs

Agents that Modulate Peritoneal Membrane Structure and Function

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