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

Research output: Contribution to journalArticle

53 Scopus citations

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-κ 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.

Original languageEnglish (US)
Pages (from-to)695-706
Number of pages12
JournalBasic Research in Cardiology
Volume104
Issue number6
DOIs
StatePublished - 2009

Keywords

  • Early atherosclerosis
  • Inflammation
  • Micro-CT
  • Neovascularization
  • Vasa vasorum

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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