Low vasa vasorum densities correlate with inflammation and subintimal thickening: Potential role in location—Determination of atherogenesis

Gössl, M.; Versari, D.; Lerman, L.O.; Chade, A.R.; Beighley, P.E.; Erbel, R.; Ritman, E.L.

doi:10.1016/j.atherosclerosis.2009.03.010

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Volume 206, Issue 2 , Pages 362-368, October 2009

Low vasa vasorum densities correlate with inflammation and subintimal thickening: Potential role in location—Determination of atherogenesis

In memoriam of Ms. Patricia Beighley who died November 23rd 2008.

M. Gössl
- Department of Internal Medicine, Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN 55905, United States
D. Versari
- Department of Internal Medicine, Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN 55905, United States
L.O. Lerman
- Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN 55905, United States
A.R. Chade
- Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN 55905, United States
P.E. Beighley
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, United States
R. Erbel
- University Duisburg-Essen, West German Heart Center, Hufelandstr. 55, 45122 Essen, Germany
E.L. Ritman
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, United States
- Corresponding author at: Department of Physiology and Biomedical Engineering, Alfred 2-409, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Tel.: +1 507 255 1933; fax: +1 507 255 1935.

Received 25 November 2006; received in revised form 25 February 2009; accepted 5 March 2009. published online 15 April 2009.

Abstract

Objectives

To assess the role of coronary vasa vasorum (VV) spatial distribution in determining the location of early atherosclerotic lesion development.

Methods and results

Six, 3-month-old, female, crossbred swine were fed 2% high-cholesterol (HC) diet for 3 months prior to euthanasia. Six other pigs were fed normal diet (N) for the entire 6 months. Right coronary arteries were harvested and scanned intact with micro-CT (20μm cubic-voxel-size). After scanning, randomly selected cross-sectional histological sections were stained for nuclear-factor kappaB (NF-κB), hypoxia-inducible factor-1alpha (HIF-1α), macrophages, von-Willebrand-factor, dihydroethidium (DHE), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The number of positive stained cells, as well as intima-to-media ratio, were compared with VV density (#/mm²) obtained from micro-CT images (which closely matched the location of the histological sections) in each of four equal quadrants of the coronary vessel wall. In normal, as well as HC pigs, the number of NF-κB (r=0.73 and 0.70), HIF-1α (r=0.74 and 0.77), TNF-α (r=0.58 and 0.72) and IL-6 (r=0.70 and 0.72) positive cells as well as the expression of DHE (Kendall tau coefficient −0.64 and −0.63) inversely correlated with VV density. In HC the VV density also inversely correlated with intima/media ratios (r=0.65).

Conclusions

Our data suggest that low VV density territories within the coronary vessel wall are susceptible to hypoxia, oxidative stress and microinflammation and may therefore be starting points of early atherogenesis.

Keywords: Atherogenesis, Hypoxia, Microinflammation, Micro-CT, Vasa vasorum