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Impaired collateral recruitment and outward remodeling in experimental diabetes.

van Golde JM, Ruiter MS, Schaper NC, Vöö S, Waltenberger J, Backes WH, Post MJ, Huijberts MS - Diabetes (2008)

Bottom Line: Likewise, a reduced blood volume index in the region of growing collaterals was observed in diabetic animals.The monocyte migration toward vascular endothelial growth factor-A and monocyte chemotactic protein-1 was strongly reduced in diabetic rabbits.Therapies aimed at restoring acute collateral recruitment, such as vasodilators, may be of interest to improve collateral function in diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Centre and Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands. jmcg.vangolde@intmed.unimaas.nl

ABSTRACT

Objective: In this study, the effect of chronic hyperglycemia on acute ligation-induced collateral vasodilation, on monocyte chemotaxis, and on structural outward remodeling of collaterals was investigated.

Research design and methods: Femoral artery ligation was performed 8 weeks after alloxan or saline treatment in New Zealand White rabbits. Angiography was performed directly, 1 and 3 weeks after ligation. These angiographic recordings were used to quantify number of collaterals, lumen, and blood volume index. Reactive hyperemia response was tested by intramuscular laser Doppler measurements. Subsequently, blood was sampled from the aorta for monocyte chemotaxis.

Results: Ligation resulted in markedly lower acute collateral vasodilation in diabetic compared with control rabbits. Also, hyperemic vasodilatory response to local ischemia was impaired in diabetic rabbits. This difference persisted at 1 and 3 weeks after ligation, with a lower number of visible collaterals. In addition, the collateral lumen was markedly lower in diabetic rabbits after the maturation phase. Likewise, a reduced blood volume index in the region of growing collaterals was observed in diabetic animals. The monocyte migration toward vascular endothelial growth factor-A and monocyte chemotactic protein-1 was strongly reduced in diabetic rabbits.

Conclusions: This study demonstrates that chronic hyperglycemia negatively affects the different phases of arteriogenesis: 1) impaired shear induced vasodilatation; 2) impaired outward collateral growth, reflected in the number of collaterals and blood volume index; and 3) inhibition of monocyte chemotaxis. Impairments were most evident in the acute phase of arteriogenesis. Therapies aimed at restoring acute collateral recruitment, such as vasodilators, may be of interest to improve collateral function in diabetes.

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Related in: MedlinePlus

Chemotactic response of monocytes toward 10 ng/ml VEGF-A, 10 ng/ml MCP-1, and 10−8 mol/l fMLP gradient. Monocytes were isolated from either diabetic () or control (□) rabbits. Data are presented as median (bold line), 25–75 percentiles (box), and 5–95 percentiles (whiskers).
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f5: Chemotactic response of monocytes toward 10 ng/ml VEGF-A, 10 ng/ml MCP-1, and 10−8 mol/l fMLP gradient. Monocytes were isolated from either diabetic () or control (□) rabbits. Data are presented as median (bold line), 25–75 percentiles (box), and 5–95 percentiles (whiskers).

Mentions: In Fig. 5, the migratory response of monocytes toward two different growth factors (VEGF-A and MCP-1) and the chemoattractant peptide (fMLP) as a positive control are shown (data are expressed as a percentage of unstimulated monocytes). In control animals, VEGF-A and MCP-1 induced a strong chemotactic response in monocytes. VEGF-A–induced migration of monocytes was twofold lower in diabetic rabbits compared with controls (P = 0.019). The same was observed for MCP-1 stimulation (P = 0.028). No difference between controls and diabetic rabbits was observed in the fMLP-induced migratory response.


Impaired collateral recruitment and outward remodeling in experimental diabetes.

van Golde JM, Ruiter MS, Schaper NC, Vöö S, Waltenberger J, Backes WH, Post MJ, Huijberts MS - Diabetes (2008)

Chemotactic response of monocytes toward 10 ng/ml VEGF-A, 10 ng/ml MCP-1, and 10−8 mol/l fMLP gradient. Monocytes were isolated from either diabetic () or control (□) rabbits. Data are presented as median (bold line), 25–75 percentiles (box), and 5–95 percentiles (whiskers).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2551694&req=5

f5: Chemotactic response of monocytes toward 10 ng/ml VEGF-A, 10 ng/ml MCP-1, and 10−8 mol/l fMLP gradient. Monocytes were isolated from either diabetic () or control (□) rabbits. Data are presented as median (bold line), 25–75 percentiles (box), and 5–95 percentiles (whiskers).
Mentions: In Fig. 5, the migratory response of monocytes toward two different growth factors (VEGF-A and MCP-1) and the chemoattractant peptide (fMLP) as a positive control are shown (data are expressed as a percentage of unstimulated monocytes). In control animals, VEGF-A and MCP-1 induced a strong chemotactic response in monocytes. VEGF-A–induced migration of monocytes was twofold lower in diabetic rabbits compared with controls (P = 0.019). The same was observed for MCP-1 stimulation (P = 0.028). No difference between controls and diabetic rabbits was observed in the fMLP-induced migratory response.

Bottom Line: Likewise, a reduced blood volume index in the region of growing collaterals was observed in diabetic animals.The monocyte migration toward vascular endothelial growth factor-A and monocyte chemotactic protein-1 was strongly reduced in diabetic rabbits.Therapies aimed at restoring acute collateral recruitment, such as vasodilators, may be of interest to improve collateral function in diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Centre and Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands. jmcg.vangolde@intmed.unimaas.nl

ABSTRACT

Objective: In this study, the effect of chronic hyperglycemia on acute ligation-induced collateral vasodilation, on monocyte chemotaxis, and on structural outward remodeling of collaterals was investigated.

Research design and methods: Femoral artery ligation was performed 8 weeks after alloxan or saline treatment in New Zealand White rabbits. Angiography was performed directly, 1 and 3 weeks after ligation. These angiographic recordings were used to quantify number of collaterals, lumen, and blood volume index. Reactive hyperemia response was tested by intramuscular laser Doppler measurements. Subsequently, blood was sampled from the aorta for monocyte chemotaxis.

Results: Ligation resulted in markedly lower acute collateral vasodilation in diabetic compared with control rabbits. Also, hyperemic vasodilatory response to local ischemia was impaired in diabetic rabbits. This difference persisted at 1 and 3 weeks after ligation, with a lower number of visible collaterals. In addition, the collateral lumen was markedly lower in diabetic rabbits after the maturation phase. Likewise, a reduced blood volume index in the region of growing collaterals was observed in diabetic animals. The monocyte migration toward vascular endothelial growth factor-A and monocyte chemotactic protein-1 was strongly reduced in diabetic rabbits.

Conclusions: This study demonstrates that chronic hyperglycemia negatively affects the different phases of arteriogenesis: 1) impaired shear induced vasodilatation; 2) impaired outward collateral growth, reflected in the number of collaterals and blood volume index; and 3) inhibition of monocyte chemotaxis. Impairments were most evident in the acute phase of arteriogenesis. Therapies aimed at restoring acute collateral recruitment, such as vasodilators, may be of interest to improve collateral function in diabetes.

Show MeSH
Related in: MedlinePlus