title: Differential impact of diabetes mellitus type II and arterial hypertension on collateral artery growth and concomitant macrophage accumulation.
abstract: BACKGROUND
  Diabetes mellitus type II and arterial hypertension are major risk factors for peripheral arterial disease and have been considered to reduce collateral growth (arteriogenesis). Collateral growth proceeds through different stages. Vascular proliferation and macrophage accumulation are hallmarks of early collateral growth.
  
  
  METHODS
  We here compare the impact of arterial hypertension and diabetes mellitus type II on collateral proliferation (Brdu incorporation) and macrophage accumulation (ED 2 staining) as well as collateral vessel function (collateral conductance) in a rat model of peripheral vascular disease (femoral artery occlusion), diabetes mellitus type II (Zucker fatty diabetic rats and Zucker lean rat controls) and arterial hypertension (induced via clip placement around the right renal arteriy). We furthermore tested the impact of monocyte chemoattractant protein-1 (MCP‑1) on collateral proliferation and macrophage accumulation in these models
  
  
  RESULTS
  Diabetic animals showed reduced vascular proliferation and macrophage accumulation, which however did not translate into a change of collateral conductance. Hypertensive animals on the contrary had reduced collateral conductances without altered macrophage accumulation and only a marginal reduction in collateral proliferation. Infusion of MCP‑1 only enhanced vascular proliferation in diabetic animals.
  
  
  CONCLUSIONS
  These findings illustrate that impaired monocyte/macrophage recruitment is responsible for reduced collateral growth under diabetic conditions but not in arterial hypertension suggesting that diabetes mellitus in particular affects early stages of collateral growth whereas hypertension has its impact on later remodeling stages. Successful pro-arteriogenic treatment strategies in a patient population that presents with diabetes mellitus and arterial hypertension need to address different stages of collateral growth and thus different molecular and cellular targets simultaneously.
authors.affiliation: Herz und Gefäßzentrum Oberallgäu-Kempten, Immenstadt, Germany.
authors.forename: Wulf D
authors.initials: WD
authors.lastname: Ito
authors.affiliation: University Heart Center, Division of Cardiology University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Lund
authors.affiliation: University Heart Center, Division of Cardiology University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Sager
authors.affiliation: University Heart Center, Division of Cardiology University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Becker
authors.affiliation: Department of Medicine, Division of Nephrology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wenzel
mesh_terms: D000818:Animals; D001158:Arteries / Q000254:growth & development / Q000503:physiopathology; D003097:Collateral Circulation / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000276:immunology / Q000503:physiopathology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000276:immunology / Q000503:physiopathology*; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D009765:Obesity / Q000276:immunology / Q000503:physiopathology; D011924:Rats, Zucker
keywords: Collateral growth; arterial hypertension; arteriogenesis; diabetes mellitus type II; macrophage accumulation; vascular proliferation