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

Mario Gössl, Joerg Herrmann, Hui Tang, Daniele Versari, Offer Galili, Dallit Mannheim, S Vincent Rajkumar, Lilach O Lerman, Amir Lerman

Research output: Contribution to journalArticle

53 Citations (Scopus)

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

Fingerprint

Vasa Vasorum
Neointima
Thalidomide
Hypercholesterolemia
Vascular Endothelial Growth Factor A
Atherosclerosis
Coronary Vessels
Swine
Diet
Angiogenesis Inhibitors
Electrophoretic Mobility Shift Assay
Fluorescent Antibody Technique
Western Blotting
Cholesterol
Inflammation

Keywords

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

ASJC Scopus subject areas

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

Cite this

Prevention of vasa vasorum neovascularization attenuates early neointima formation in experimental hypercholesterolemia. / Gössl, Mario; Herrmann, Joerg; Tang, Hui; Versari, Daniele; Galili, Offer; Mannheim, Dallit; Rajkumar, S Vincent; Lerman, Lilach O; Lerman, Amir.

In: Basic Research in Cardiology, Vol. 104, No. 6, 2009, p. 695-706.

Research output: Contribution to journalArticle

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