Simvastatin preserves the structure of coronary adventitial vasa vasorum in experimental hypercholesterolemia independent of lipid lowering

Stephanie H. Wilson, Joerg Herrmann, Lilach O Lerman, David Holmes, Claudio Napoli, Erik L. Ritman, Amir Lerman

Research output: Contribution to journalArticle

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Abstract

Background - Previous studies have demonstrated that experimental hypercholesterolemia leads to neovascularization in the coronary artery vasa vasorum (VV). Recent evidence suggests that HMG-CoA reductase inhibitors (statins) have beneficial effects independent of lipid lowering. We aimed to determine the effect of simvastatin on coronary VV neovascularization, in the absence of cholesterol lowering. Methods and Results - Pigs were randomized to 3 groups fed a normal (N), high cholesterol (HC), or HC + simvastatin (HC+S) diet for 12 weeks. The proximal left anterior descending artery was isolated, scanned with micro-CT, and reconstructed. Quantification of the VV density in serial cross-sections along the vessel was then performed. LDL cholesterol was similarly increased in HC and HC+S compared with N. There was an increase in both VV density (4.7±0.3 versus 2.7±0.2 n/mm2; P<0.05) and vessel wall area (3.1±0.2 versus 1.8±0.1 mm2; P<0.05) in HC compared with N. The VV density in HC+S was preserved compared with HC (3.0±0.2 n/mm2; P<0.05), despite similar increase in vessel wall area compared with N (2.5±0.1 mm2; P<0.05). Coronary artery tissue expression of VEGF was increased in HC but not in HC+S compared with N. In parallel, immunoreactivity for HIF-1α, VEGF, MMP-2, and MMP-9 was accentuated in the outer media in HC but not in HC+S compared with N. Conclusions - This study demonstrates that simvastatin attenuates hypoxia in the coronary artery wall and VV neovascularization in experimental hypercholesterolemia, despite no change in plasma lipids. These data are consistent with an additional mechanism for the vascular effects of the statins, independent of cholesterol lowering.

Original languageEnglish (US)
Pages (from-to)415-418
Number of pages4
JournalCirculation
Volume105
Issue number4
DOIs
StatePublished - Jan 29 2002

Fingerprint

Vasa Vasorum
Adventitia
Simvastatin
Hypercholesterolemia
Cholesterol
Lipids
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Coronary Vessels
Matrix Metalloproteinases
Vascular Endothelial Growth Factor A

Keywords

  • Hypercholesterolemia
  • Pathological neovascularization
  • Statins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Simvastatin preserves the structure of coronary adventitial vasa vasorum in experimental hypercholesterolemia independent of lipid lowering. / Wilson, Stephanie H.; Herrmann, Joerg; Lerman, Lilach O; Holmes, David; Napoli, Claudio; Ritman, Erik L.; Lerman, Amir.

In: Circulation, Vol. 105, No. 4, 29.01.2002, p. 415-418.

Research output: Contribution to journalArticle

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abstract = "Background - Previous studies have demonstrated that experimental hypercholesterolemia leads to neovascularization in the coronary artery vasa vasorum (VV). Recent evidence suggests that HMG-CoA reductase inhibitors (statins) have beneficial effects independent of lipid lowering. We aimed to determine the effect of simvastatin on coronary VV neovascularization, in the absence of cholesterol lowering. Methods and Results - Pigs were randomized to 3 groups fed a normal (N), high cholesterol (HC), or HC + simvastatin (HC+S) diet for 12 weeks. The proximal left anterior descending artery was isolated, scanned with micro-CT, and reconstructed. Quantification of the VV density in serial cross-sections along the vessel was then performed. LDL cholesterol was similarly increased in HC and HC+S compared with N. There was an increase in both VV density (4.7±0.3 versus 2.7±0.2 n/mm2; P<0.05) and vessel wall area (3.1±0.2 versus 1.8±0.1 mm2; P<0.05) in HC compared with N. The VV density in HC+S was preserved compared with HC (3.0±0.2 n/mm2; P<0.05), despite similar increase in vessel wall area compared with N (2.5±0.1 mm2; P<0.05). Coronary artery tissue expression of VEGF was increased in HC but not in HC+S compared with N. In parallel, immunoreactivity for HIF-1α, VEGF, MMP-2, and MMP-9 was accentuated in the outer media in HC but not in HC+S compared with N. Conclusions - This study demonstrates that simvastatin attenuates hypoxia in the coronary artery wall and VV neovascularization in experimental hypercholesterolemia, despite no change in plasma lipids. These data are consistent with an additional mechanism for the vascular effects of the statins, independent of cholesterol lowering.",
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AU - Wilson, Stephanie H.

AU - Herrmann, Joerg

AU - Lerman, Lilach O

AU - Holmes, David

AU - Napoli, Claudio

AU - Ritman, Erik L.

AU - Lerman, Amir

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N2 - Background - Previous studies have demonstrated that experimental hypercholesterolemia leads to neovascularization in the coronary artery vasa vasorum (VV). Recent evidence suggests that HMG-CoA reductase inhibitors (statins) have beneficial effects independent of lipid lowering. We aimed to determine the effect of simvastatin on coronary VV neovascularization, in the absence of cholesterol lowering. Methods and Results - Pigs were randomized to 3 groups fed a normal (N), high cholesterol (HC), or HC + simvastatin (HC+S) diet for 12 weeks. The proximal left anterior descending artery was isolated, scanned with micro-CT, and reconstructed. Quantification of the VV density in serial cross-sections along the vessel was then performed. LDL cholesterol was similarly increased in HC and HC+S compared with N. There was an increase in both VV density (4.7±0.3 versus 2.7±0.2 n/mm2; P<0.05) and vessel wall area (3.1±0.2 versus 1.8±0.1 mm2; P<0.05) in HC compared with N. The VV density in HC+S was preserved compared with HC (3.0±0.2 n/mm2; P<0.05), despite similar increase in vessel wall area compared with N (2.5±0.1 mm2; P<0.05). Coronary artery tissue expression of VEGF was increased in HC but not in HC+S compared with N. In parallel, immunoreactivity for HIF-1α, VEGF, MMP-2, and MMP-9 was accentuated in the outer media in HC but not in HC+S compared with N. Conclusions - This study demonstrates that simvastatin attenuates hypoxia in the coronary artery wall and VV neovascularization in experimental hypercholesterolemia, despite no change in plasma lipids. These data are consistent with an additional mechanism for the vascular effects of the statins, independent of cholesterol lowering.

AB - Background - Previous studies have demonstrated that experimental hypercholesterolemia leads to neovascularization in the coronary artery vasa vasorum (VV). Recent evidence suggests that HMG-CoA reductase inhibitors (statins) have beneficial effects independent of lipid lowering. We aimed to determine the effect of simvastatin on coronary VV neovascularization, in the absence of cholesterol lowering. Methods and Results - Pigs were randomized to 3 groups fed a normal (N), high cholesterol (HC), or HC + simvastatin (HC+S) diet for 12 weeks. The proximal left anterior descending artery was isolated, scanned with micro-CT, and reconstructed. Quantification of the VV density in serial cross-sections along the vessel was then performed. LDL cholesterol was similarly increased in HC and HC+S compared with N. There was an increase in both VV density (4.7±0.3 versus 2.7±0.2 n/mm2; P<0.05) and vessel wall area (3.1±0.2 versus 1.8±0.1 mm2; P<0.05) in HC compared with N. The VV density in HC+S was preserved compared with HC (3.0±0.2 n/mm2; P<0.05), despite similar increase in vessel wall area compared with N (2.5±0.1 mm2; P<0.05). Coronary artery tissue expression of VEGF was increased in HC but not in HC+S compared with N. In parallel, immunoreactivity for HIF-1α, VEGF, MMP-2, and MMP-9 was accentuated in the outer media in HC but not in HC+S compared with N. Conclusions - This study demonstrates that simvastatin attenuates hypoxia in the coronary artery wall and VV neovascularization in experimental hypercholesterolemia, despite no change in plasma lipids. These data are consistent with an additional mechanism for the vascular effects of the statins, independent of cholesterol lowering.

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