Impaired collateral recruitment and outward remodelling in experimental diabetes

Abstract

Objective. In this study the effect of chronic hyperglycemia on acute ligation induced collateral vasodilation, monocyte chemotaxis and on structural outward remodelling 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, one week and three weeks after ligation. These angiographic recordings were used to quantify number of collaterals, lumen and blood volume index. Reactive hyperaemia 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 to control rabbits. Also hyperaemic vasodilatory response to local ischemia was impaired in diabetic rabbits. This difference persisted at one and three weeks after ligation, with 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 towards VEGF-A and MCP-1 was strongly reduced in diabetic rabbits.

Conclusions. This study demonstrates that chronic hyperglycemia negatively affects the different phases of arteriogenesis: a) impaired shear induced vasodilatation, b) impaired outward collateral growth, reflected in the number of collaterals and blood volume index, c) 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.