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Hyperglycemia-Induced Changes in Hyaluronan Contribute to Impaired Skin Wound Healing in Diabetes: Review and Perspective.

Shakya S, Wang Y, Mack JA, Maytin EV - Int J Cell Biol (2015)

Bottom Line: Ulcers and chronic wounds are a particularly common problem in diabetics and are associated with hyperglycemia.In this targeted review, we summarize evidence suggesting that defective wound healing in diabetics is causally linked, at least in part, to hyperglycemia-induced changes in the status of hyaluronan (HA) that resides in the pericellular coat (glycocalyx) of endothelial cells of small cutaneous blood vessels.Possible roles of newly recognized, cross-linked forms of HA, and interactions of a major HA receptor (CD44) with cytokine/growth factor receptors during hyperglycemia, are also discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

ABSTRACT
Ulcers and chronic wounds are a particularly common problem in diabetics and are associated with hyperglycemia. In this targeted review, we summarize evidence suggesting that defective wound healing in diabetics is causally linked, at least in part, to hyperglycemia-induced changes in the status of hyaluronan (HA) that resides in the pericellular coat (glycocalyx) of endothelial cells of small cutaneous blood vessels. Potential mechanisms through which exposure to high glucose levels causes a loss of the glycocalyx on the endothelium and accelerates the recruitment of leukocytes, creating a proinflammatory environment, are discussed in detail. Hyperglycemia also affects other cells in the immediate perivascular area, including pericytes and smooth muscle cells, through exposure to increased cytokine levels and through glucose elevations in the interstitial fluid. Possible roles of newly recognized, cross-linked forms of HA, and interactions of a major HA receptor (CD44) with cytokine/growth factor receptors during hyperglycemia, are also discussed.

No MeSH data available.


Related in: MedlinePlus

Summary of hyperglycemia-induced changes, within blood vessels and in their immediate surroundings, that involve alterations in HA.
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fig3: Summary of hyperglycemia-induced changes, within blood vessels and in their immediate surroundings, that involve alterations in HA.

Mentions: In this review, we have discussed current evidence regarding mechanisms by which altered hyaluronan (HA) in microvessels of the skin may lead to poor wound healing in diabetic patients. These ideas are summarized in Figure 3. The major premise is that hyperglycemia causes loss of the HA-containing glycocalyx on endothelial surfaces of cutaneous microvessels, leading to increased leukocyte adhesiveness and triggering the release of cytokines that contribute to a proinflammatory environment. Such changes are likely to increase oxidative damage, decrease proper responsiveness of vascular ECs, and impede neoangiogenesis and other repair responses during the tissue regenerative phase of wound healing. Other cell types at or near the blood vessel wall, including pericytes, smooth muscle cells, and fibroblasts, are also adversely affected by hyperglycemia and the cytokine-rich environment but through different mechanisms. One mechanism may be an enhanced sensitivity to profibrotic cytokines such as TGF-β, whose receptors interact with CD44 and with HA in the glycocalyx of the mesenchymal cells. A better understanding of hyperglycemia-related mechanisms in the skin is a worthy goal, as it may suggest new approaches to heal or prevent skin ulcers in patients with diabetes.


Hyperglycemia-Induced Changes in Hyaluronan Contribute to Impaired Skin Wound Healing in Diabetes: Review and Perspective.

Shakya S, Wang Y, Mack JA, Maytin EV - Int J Cell Biol (2015)

Summary of hyperglycemia-induced changes, within blood vessels and in their immediate surroundings, that involve alterations in HA.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4581551&req=5

fig3: Summary of hyperglycemia-induced changes, within blood vessels and in their immediate surroundings, that involve alterations in HA.
Mentions: In this review, we have discussed current evidence regarding mechanisms by which altered hyaluronan (HA) in microvessels of the skin may lead to poor wound healing in diabetic patients. These ideas are summarized in Figure 3. The major premise is that hyperglycemia causes loss of the HA-containing glycocalyx on endothelial surfaces of cutaneous microvessels, leading to increased leukocyte adhesiveness and triggering the release of cytokines that contribute to a proinflammatory environment. Such changes are likely to increase oxidative damage, decrease proper responsiveness of vascular ECs, and impede neoangiogenesis and other repair responses during the tissue regenerative phase of wound healing. Other cell types at or near the blood vessel wall, including pericytes, smooth muscle cells, and fibroblasts, are also adversely affected by hyperglycemia and the cytokine-rich environment but through different mechanisms. One mechanism may be an enhanced sensitivity to profibrotic cytokines such as TGF-β, whose receptors interact with CD44 and with HA in the glycocalyx of the mesenchymal cells. A better understanding of hyperglycemia-related mechanisms in the skin is a worthy goal, as it may suggest new approaches to heal or prevent skin ulcers in patients with diabetes.

Bottom Line: Ulcers and chronic wounds are a particularly common problem in diabetics and are associated with hyperglycemia.In this targeted review, we summarize evidence suggesting that defective wound healing in diabetics is causally linked, at least in part, to hyperglycemia-induced changes in the status of hyaluronan (HA) that resides in the pericellular coat (glycocalyx) of endothelial cells of small cutaneous blood vessels.Possible roles of newly recognized, cross-linked forms of HA, and interactions of a major HA receptor (CD44) with cytokine/growth factor receptors during hyperglycemia, are also discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

ABSTRACT
Ulcers and chronic wounds are a particularly common problem in diabetics and are associated with hyperglycemia. In this targeted review, we summarize evidence suggesting that defective wound healing in diabetics is causally linked, at least in part, to hyperglycemia-induced changes in the status of hyaluronan (HA) that resides in the pericellular coat (glycocalyx) of endothelial cells of small cutaneous blood vessels. Potential mechanisms through which exposure to high glucose levels causes a loss of the glycocalyx on the endothelium and accelerates the recruitment of leukocytes, creating a proinflammatory environment, are discussed in detail. Hyperglycemia also affects other cells in the immediate perivascular area, including pericytes and smooth muscle cells, through exposure to increased cytokine levels and through glucose elevations in the interstitial fluid. Possible roles of newly recognized, cross-linked forms of HA, and interactions of a major HA receptor (CD44) with cytokine/growth factor receptors during hyperglycemia, are also discussed.

No MeSH data available.


Related in: MedlinePlus