Basic Research in Cardiology

, 104:695

Prevention of vasa vasorum neovascularization attenuates early neointima formation in experimental hypercholesterolemia

  • Mario Gössl
  • Jörg Herrmann
  • Hui Tang
  • Daniele Versari
  • Offer Galili
  • Dallit Mannheim
  • S. Vincent Rajkumar
  • Lilach O. Lerman
  • Amir Lerman
Original Contribution

Abstract

Vasa vasorum (VV) neovascularization is a key feature of early atherosclerosis and adds substantial endothelial exchange-surface to the coronary vessel wall. Thus, it is conceivable that VV neovascularization favors the entry of pro-inflammatory and pro-atherosclerotic blood components into the coronary vessel wall. We sought to investigate the effects of Thalidomide (Th), a potent anti-angiogenic drug on vasa vasorum (VV) neovascularization, vessel wall inflammation, and neointima formation in early experimental atherosclerosis. Female domestic swine, 3 months old, were fed normal (N, n = 12) or high-cholesterol diet (HC, n = 12) for 3 months. In each group six pigs were randomized to 200 mg Thalidomide daily for the diet period (N + Th, HC + Th). LADs were scanned with micro-CT (20 μm cubic voxel size) to determine VV spatial density (#/mm²). Fresh-frozen coronary tissue was used for western blotting (VEGF, TNF-α, LOX-1, Iκβα and Gro-α) and electrophoretic mobility shift assay (EMSA, NFκβ). Treatment with Thalidomide preserved VV spatial density [2.7 ± 0.3 (N), 6.4 ± 0.7 (HC), 3.5 ± 0.8 (HC + Th); p = ns HC + Th vs. N] and inhibited the expression of VEGF, TNF-α and LOX-1, but not NFκβ activity in the coronary vessel wall. Immunofluorescence analyses revealed co-localization of vWF but not SMA and NFκβ, TNF-α as well as VEGF in HC and HC + Th coronaries. Intima-media thickness was significantly inhibited in HC + Th compared to HC. Serum levels of hs-CRP and TNF-α did not differ among the groups. Our study supports a role of VV neovascularization in the development of and a therapeutic potential for anti-angiogenic intervention in early atherosclerosis.

Keywords

Vasa vasorum Early atherosclerosis Micro-CT Neovascularization Inflammation 

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Mario Gössl
    • 1
  • Jörg Herrmann
    • 1
  • Hui Tang
    • 2
  • Daniele Versari
    • 1
  • Offer Galili
    • 1
  • Dallit Mannheim
    • 1
  • S. Vincent Rajkumar
    • 3
  • Lilach O. Lerman
    • 2
  • Amir Lerman
    • 1
  1. 1.Division of Cardiovascular DiseasesMayo Clinic College of MedicineRochesterUSA
  2. 2.Division of Nephrology and HypertensionMayo Clinic College of MedicineRochesterUSA
  3. 3.Division of HematologyMayo Clinic College of MedicineRochesterUSA

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