Increased spatial vasa vasorum density in the proximal LAD in hypercholesterolemia-Implications for vulnerable plaque-development

Mario Gössl, Daniele Versari, Dallit Mannheim, Erik L. Ritman, Lilach O Lerman, Amir Lerman

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Abstract

Objective: Vasa vasorum (VV) neovascularization is associated with advanced and ruptured atherosclerotic lesions that occur predominantly within the proximal third of the LAD. To investigate further the possible role of VV spatial distribution in determining this predominantly proximal location of complex lesions we analyzed the changes in VV spatial densities along the LAD in early atherosclerosis. Methods and results: Three-month-old, female domestic pigs were placed on normal (N; n = 6) or high-cholesterol (HC; n = 6) diet for 3 months. VV count, vascular-area-fraction (∑vasa vasorum areas/mm2 vessel wall area, i.e., flow capacity), and the endothelial-surface-fraction (∑vasa vasorum endothelial surfaces/mm3 vessel wall volume) were calculated in three equal thirds of the coronary artery from microcomputed-tomography images. In N animals, the proximal thirds tended to have a higher vascular-area-fraction (mean ± S.D., 1.4 ± 0.6 versus 0.9 ± 0.3 and 0.9 ± 0.2%; P = 0.1) and endothelial-surface-fraction (0.72 ± 0.29 versus 0.59 ± 0.22 and 0.53 ± 0.20 mm2/mm3; NS) than the mid and distal thirds with significantly higher VV counts (26 ± 12, 15 ± 8, 8 ± 5, P = 0.01). In HC animals, we observed significant VV neovascularization (3.3 ± 1.2 n/mm2 versus 6.8 ± 1.9 n/mm2, P < 0.01), with significantly higher VV counts (24 ± 3 and 14 ± 3 versus 6 ± 4; P < 0.001) as well as higher vascular-area- (1.4 ± 0.2 and 1.4 ± 0.2% versus 0.8 ± 0.2%; P < 0.001) and endothelial-surface-fractions (0.88 ± 0.14 and 0.90 ± 0.12 mm2/mm3 versus 0.56 ± 0.14 mm2/mm3; P = 0.001) within the proximal and middle thirds compared to the distal third. Conclusions: VV neovascularization in early atherosclerosis leads to a proximally accentuated increase in flow-capacity and endothelial-exchange-surface, which may favour the predominant development of vulnerable atherosclerotic plaques in proximal portions of the LAD.

Original languageEnglish (US)
Pages (from-to)246-252
Number of pages7
JournalAtherosclerosis
Volume192
Issue number2
DOIs
StatePublished - Jun 2007

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Vasa Vasorum
Hypercholesterolemia
Blood Vessels
Atherosclerosis
X-Ray Microtomography
Sus scrofa
Atherosclerotic Plaques
Coronary Vessels
Cholesterol

Keywords

  • Acute coronary syndromes
  • Hypercholesterolemia
  • Micro-CT
  • Neovascularization
  • Vasa vasorum

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Increased spatial vasa vasorum density in the proximal LAD in hypercholesterolemia-Implications for vulnerable plaque-development. / Gössl, Mario; Versari, Daniele; Mannheim, Dallit; Ritman, Erik L.; Lerman, Lilach O; Lerman, Amir.

In: Atherosclerosis, Vol. 192, No. 2, 06.2007, p. 246-252.

Research output: Contribution to journalArticle

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title = "Increased spatial vasa vasorum density in the proximal LAD in hypercholesterolemia-Implications for vulnerable plaque-development",
abstract = "Objective: Vasa vasorum (VV) neovascularization is associated with advanced and ruptured atherosclerotic lesions that occur predominantly within the proximal third of the LAD. To investigate further the possible role of VV spatial distribution in determining this predominantly proximal location of complex lesions we analyzed the changes in VV spatial densities along the LAD in early atherosclerosis. Methods and results: Three-month-old, female domestic pigs were placed on normal (N; n = 6) or high-cholesterol (HC; n = 6) diet for 3 months. VV count, vascular-area-fraction (∑vasa vasorum areas/mm2 vessel wall area, i.e., flow capacity), and the endothelial-surface-fraction (∑vasa vasorum endothelial surfaces/mm3 vessel wall volume) were calculated in three equal thirds of the coronary artery from microcomputed-tomography images. In N animals, the proximal thirds tended to have a higher vascular-area-fraction (mean ± S.D., 1.4 ± 0.6 versus 0.9 ± 0.3 and 0.9 ± 0.2{\%}; P = 0.1) and endothelial-surface-fraction (0.72 ± 0.29 versus 0.59 ± 0.22 and 0.53 ± 0.20 mm2/mm3; NS) than the mid and distal thirds with significantly higher VV counts (26 ± 12, 15 ± 8, 8 ± 5, P = 0.01). In HC animals, we observed significant VV neovascularization (3.3 ± 1.2 n/mm2 versus 6.8 ± 1.9 n/mm2, P < 0.01), with significantly higher VV counts (24 ± 3 and 14 ± 3 versus 6 ± 4; P < 0.001) as well as higher vascular-area- (1.4 ± 0.2 and 1.4 ± 0.2{\%} versus 0.8 ± 0.2{\%}; P < 0.001) and endothelial-surface-fractions (0.88 ± 0.14 and 0.90 ± 0.12 mm2/mm3 versus 0.56 ± 0.14 mm2/mm3; P = 0.001) within the proximal and middle thirds compared to the distal third. Conclusions: VV neovascularization in early atherosclerosis leads to a proximally accentuated increase in flow-capacity and endothelial-exchange-surface, which may favour the predominant development of vulnerable atherosclerotic plaques in proximal portions of the LAD.",
keywords = "Acute coronary syndromes, Hypercholesterolemia, Micro-CT, Neovascularization, Vasa vasorum",
author = "Mario G{\"o}ssl and Daniele Versari and Dallit Mannheim and Ritman, {Erik L.} and Lerman, {Lilach O} and Amir Lerman",
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T1 - Increased spatial vasa vasorum density in the proximal LAD in hypercholesterolemia-Implications for vulnerable plaque-development

AU - Gössl, Mario

AU - Versari, Daniele

AU - Mannheim, Dallit

AU - Ritman, Erik L.

AU - Lerman, Lilach O

AU - Lerman, Amir

PY - 2007/6

Y1 - 2007/6

N2 - Objective: Vasa vasorum (VV) neovascularization is associated with advanced and ruptured atherosclerotic lesions that occur predominantly within the proximal third of the LAD. To investigate further the possible role of VV spatial distribution in determining this predominantly proximal location of complex lesions we analyzed the changes in VV spatial densities along the LAD in early atherosclerosis. Methods and results: Three-month-old, female domestic pigs were placed on normal (N; n = 6) or high-cholesterol (HC; n = 6) diet for 3 months. VV count, vascular-area-fraction (∑vasa vasorum areas/mm2 vessel wall area, i.e., flow capacity), and the endothelial-surface-fraction (∑vasa vasorum endothelial surfaces/mm3 vessel wall volume) were calculated in three equal thirds of the coronary artery from microcomputed-tomography images. In N animals, the proximal thirds tended to have a higher vascular-area-fraction (mean ± S.D., 1.4 ± 0.6 versus 0.9 ± 0.3 and 0.9 ± 0.2%; P = 0.1) and endothelial-surface-fraction (0.72 ± 0.29 versus 0.59 ± 0.22 and 0.53 ± 0.20 mm2/mm3; NS) than the mid and distal thirds with significantly higher VV counts (26 ± 12, 15 ± 8, 8 ± 5, P = 0.01). In HC animals, we observed significant VV neovascularization (3.3 ± 1.2 n/mm2 versus 6.8 ± 1.9 n/mm2, P < 0.01), with significantly higher VV counts (24 ± 3 and 14 ± 3 versus 6 ± 4; P < 0.001) as well as higher vascular-area- (1.4 ± 0.2 and 1.4 ± 0.2% versus 0.8 ± 0.2%; P < 0.001) and endothelial-surface-fractions (0.88 ± 0.14 and 0.90 ± 0.12 mm2/mm3 versus 0.56 ± 0.14 mm2/mm3; P = 0.001) within the proximal and middle thirds compared to the distal third. Conclusions: VV neovascularization in early atherosclerosis leads to a proximally accentuated increase in flow-capacity and endothelial-exchange-surface, which may favour the predominant development of vulnerable atherosclerotic plaques in proximal portions of the LAD.

AB - Objective: Vasa vasorum (VV) neovascularization is associated with advanced and ruptured atherosclerotic lesions that occur predominantly within the proximal third of the LAD. To investigate further the possible role of VV spatial distribution in determining this predominantly proximal location of complex lesions we analyzed the changes in VV spatial densities along the LAD in early atherosclerosis. Methods and results: Three-month-old, female domestic pigs were placed on normal (N; n = 6) or high-cholesterol (HC; n = 6) diet for 3 months. VV count, vascular-area-fraction (∑vasa vasorum areas/mm2 vessel wall area, i.e., flow capacity), and the endothelial-surface-fraction (∑vasa vasorum endothelial surfaces/mm3 vessel wall volume) were calculated in three equal thirds of the coronary artery from microcomputed-tomography images. In N animals, the proximal thirds tended to have a higher vascular-area-fraction (mean ± S.D., 1.4 ± 0.6 versus 0.9 ± 0.3 and 0.9 ± 0.2%; P = 0.1) and endothelial-surface-fraction (0.72 ± 0.29 versus 0.59 ± 0.22 and 0.53 ± 0.20 mm2/mm3; NS) than the mid and distal thirds with significantly higher VV counts (26 ± 12, 15 ± 8, 8 ± 5, P = 0.01). In HC animals, we observed significant VV neovascularization (3.3 ± 1.2 n/mm2 versus 6.8 ± 1.9 n/mm2, P < 0.01), with significantly higher VV counts (24 ± 3 and 14 ± 3 versus 6 ± 4; P < 0.001) as well as higher vascular-area- (1.4 ± 0.2 and 1.4 ± 0.2% versus 0.8 ± 0.2%; P < 0.001) and endothelial-surface-fractions (0.88 ± 0.14 and 0.90 ± 0.12 mm2/mm3 versus 0.56 ± 0.14 mm2/mm3; P = 0.001) within the proximal and middle thirds compared to the distal third. Conclusions: VV neovascularization in early atherosclerosis leads to a proximally accentuated increase in flow-capacity and endothelial-exchange-surface, which may favour the predominant development of vulnerable atherosclerotic plaques in proximal portions of the LAD.

KW - Acute coronary syndromes

KW - Hypercholesterolemia

KW - Micro-CT

KW - Neovascularization

KW - Vasa vasorum

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