title: Impaired collateral recruitment and outward remodeling in experimental diabetes.
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.
  
  
  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.
authors.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
authors.forename: Jolanda M
authors.initials: JM
authors.lastname: van Golde
authors.forename: Matthijs S
authors.initials: MS
authors.lastname: Ruiter
authors.forename: Nicolaas C
authors.initials: NC
authors.lastname: Schaper
authors.forename: Stefan
authors.initials: S
authors.lastname: Vöö
authors.forename: Johannes
authors.initials: J
authors.lastname: Waltenberger
authors.forename: Walter H
authors.initials: WH
authors.lastname: Backes
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Post
authors.forename: Maya S
authors.initials: MS
authors.lastname: Huijberts
mesh_terms: D000496:Alloxan; D000792:Angiography / Q000379:methods; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology*; D003097:Collateral Circulation; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D006439:Hemodynamics; D006614:Hindlimb / Q000098:blood supply; D008026:Ligation / Q000009:adverse effects; D011817:Rabbits
chemical_list: D000496:Alloxan