Coronary vasa vasorum neovascularization precedes epicardial endothelial dysfunction in experimental hypercholesterolemia

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Abstract

Objective: Experimental hypercholesterolemia is associated with vasa vasorum neovascularization, unknown to occur before or after initial lesion formation. Thus, this study was performed to determine the temporal course of neovascularization of coronary vasa vasorum in relation to endothelial dysfunction, a hallmark of early atherosclerosis. Methods: Female domestic pigs were fed a normal diet (Group 1), a hypercholesterolemic diet for 2 and 4 weeks (Group 2), or a hypercholesterolemic diet for 6 and 12 weeks (Group 3). In vitro analysis of relaxation response to bradykinin served as an index for epicardial endothelial function. Spatial pattern and density of coronary vasa vasorum were assessed by three-dimensional microscopic computed tomography. Results: Relaxation response of coronary arteries to bradykinin was normal in both Group 1 (93±6%) and Group 2 (89±7%) but impaired in Group 3 (71±11%; P<0.05 vs. Group 1 and 2). In contrast, density of coronary vasa vasorum was significantly higher in both Group 2 (4.88±2.45 per-mm2) and Group 3 (4.50±1.37 per-mm2) compared to Group 1 (2.97±1.37 per-mm2; P<0.05 vs. Group 2 and 3). Conclusion: This study demonstrates that coronary vasa vasorum neovascularization occurs within the first weeks of experimental hypercholesterolemia and prior to the development of endothelial dysfunction of the host vessel, suggesting a role for vasa vasorum neovascularization in the initial stage of atherosclerotic vascular disease.

Original languageEnglish (US)
Pages (from-to)762-766
Number of pages5
JournalCardiovascular Research
Volume51
Issue number4
DOIs
StatePublished - 2001

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Vasa Vasorum
Hypercholesterolemia
Bradykinin
Diet
Sus scrofa
Vascular Diseases
Atherosclerosis
Coronary Vessels
Tomography

Keywords

  • Angiogenesis
  • Atherosclerosis
  • Cholesterol
  • Coronary disease
  • Endothelial function

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{0811d83c8c884cb08eac4e152c1ae200,
title = "Coronary vasa vasorum neovascularization precedes epicardial endothelial dysfunction in experimental hypercholesterolemia",
abstract = "Objective: Experimental hypercholesterolemia is associated with vasa vasorum neovascularization, unknown to occur before or after initial lesion formation. Thus, this study was performed to determine the temporal course of neovascularization of coronary vasa vasorum in relation to endothelial dysfunction, a hallmark of early atherosclerosis. Methods: Female domestic pigs were fed a normal diet (Group 1), a hypercholesterolemic diet for 2 and 4 weeks (Group 2), or a hypercholesterolemic diet for 6 and 12 weeks (Group 3). In vitro analysis of relaxation response to bradykinin served as an index for epicardial endothelial function. Spatial pattern and density of coronary vasa vasorum were assessed by three-dimensional microscopic computed tomography. Results: Relaxation response of coronary arteries to bradykinin was normal in both Group 1 (93±6{\%}) and Group 2 (89±7{\%}) but impaired in Group 3 (71±11{\%}; P<0.05 vs. Group 1 and 2). In contrast, density of coronary vasa vasorum was significantly higher in both Group 2 (4.88±2.45 per-mm2) and Group 3 (4.50±1.37 per-mm2) compared to Group 1 (2.97±1.37 per-mm2; P<0.05 vs. Group 2 and 3). Conclusion: This study demonstrates that coronary vasa vasorum neovascularization occurs within the first weeks of experimental hypercholesterolemia and prior to the development of endothelial dysfunction of the host vessel, suggesting a role for vasa vasorum neovascularization in the initial stage of atherosclerotic vascular disease.",
keywords = "Angiogenesis, Atherosclerosis, Cholesterol, Coronary disease, Endothelial function",
author = "Joerg Herrmann and Lerman, {Lilach O} and Rodriguez-Porcel, {Martin G} and David Holmes and Richardson, {Darcy M.} and Ritman, {Erik L.} and Amir Lerman",
year = "2001",
doi = "10.1016/S0008-6363(01)00347-9",
language = "English (US)",
volume = "51",
pages = "762--766",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Coronary vasa vasorum neovascularization precedes epicardial endothelial dysfunction in experimental hypercholesterolemia

AU - Herrmann, Joerg

AU - Lerman, Lilach O

AU - Rodriguez-Porcel, Martin G

AU - Holmes, David

AU - Richardson, Darcy M.

AU - Ritman, Erik L.

AU - Lerman, Amir

PY - 2001

Y1 - 2001

N2 - Objective: Experimental hypercholesterolemia is associated with vasa vasorum neovascularization, unknown to occur before or after initial lesion formation. Thus, this study was performed to determine the temporal course of neovascularization of coronary vasa vasorum in relation to endothelial dysfunction, a hallmark of early atherosclerosis. Methods: Female domestic pigs were fed a normal diet (Group 1), a hypercholesterolemic diet for 2 and 4 weeks (Group 2), or a hypercholesterolemic diet for 6 and 12 weeks (Group 3). In vitro analysis of relaxation response to bradykinin served as an index for epicardial endothelial function. Spatial pattern and density of coronary vasa vasorum were assessed by three-dimensional microscopic computed tomography. Results: Relaxation response of coronary arteries to bradykinin was normal in both Group 1 (93±6%) and Group 2 (89±7%) but impaired in Group 3 (71±11%; P<0.05 vs. Group 1 and 2). In contrast, density of coronary vasa vasorum was significantly higher in both Group 2 (4.88±2.45 per-mm2) and Group 3 (4.50±1.37 per-mm2) compared to Group 1 (2.97±1.37 per-mm2; P<0.05 vs. Group 2 and 3). Conclusion: This study demonstrates that coronary vasa vasorum neovascularization occurs within the first weeks of experimental hypercholesterolemia and prior to the development of endothelial dysfunction of the host vessel, suggesting a role for vasa vasorum neovascularization in the initial stage of atherosclerotic vascular disease.

AB - Objective: Experimental hypercholesterolemia is associated with vasa vasorum neovascularization, unknown to occur before or after initial lesion formation. Thus, this study was performed to determine the temporal course of neovascularization of coronary vasa vasorum in relation to endothelial dysfunction, a hallmark of early atherosclerosis. Methods: Female domestic pigs were fed a normal diet (Group 1), a hypercholesterolemic diet for 2 and 4 weeks (Group 2), or a hypercholesterolemic diet for 6 and 12 weeks (Group 3). In vitro analysis of relaxation response to bradykinin served as an index for epicardial endothelial function. Spatial pattern and density of coronary vasa vasorum were assessed by three-dimensional microscopic computed tomography. Results: Relaxation response of coronary arteries to bradykinin was normal in both Group 1 (93±6%) and Group 2 (89±7%) but impaired in Group 3 (71±11%; P<0.05 vs. Group 1 and 2). In contrast, density of coronary vasa vasorum was significantly higher in both Group 2 (4.88±2.45 per-mm2) and Group 3 (4.50±1.37 per-mm2) compared to Group 1 (2.97±1.37 per-mm2; P<0.05 vs. Group 2 and 3). Conclusion: This study demonstrates that coronary vasa vasorum neovascularization occurs within the first weeks of experimental hypercholesterolemia and prior to the development of endothelial dysfunction of the host vessel, suggesting a role for vasa vasorum neovascularization in the initial stage of atherosclerotic vascular disease.

KW - Angiogenesis

KW - Atherosclerosis

KW - Cholesterol

KW - Coronary disease

KW - Endothelial function

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U2 - 10.1016/S0008-6363(01)00347-9

DO - 10.1016/S0008-6363(01)00347-9

M3 - Article

VL - 51

SP - 762

EP - 766

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 4

ER -