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Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques - Implications for plaque stabilization

Crisby, Milita; Nordin Fredrikson, Gunilla LU ; Shah, Prediman K.; Yano, Juliana; Zhu, Jenny and Nilsson, Jan LU (2001) In Circulation 103(7). p.926-933
Abstract
Background--The clinical benefits of lipid lowering with statins are attributed to changes in plaque composition leading to lesion stability, but supporting clinical data from human studies are lacking. Therefore, we investigated the effect of 3 months of pravastatin treatment on composition of human carotid plaques removed during carotid endarterectomy. Methods and Results--Consecutive patients with symptomatic carotid artery stenosis received 40 mg/d pravastatin (n=11) or no lipid-lowering therapy (n=13; control subjects) for 3 months before scheduled carotid endarterectomy. Carotid Plaque composition was assessed with special stains and immunocytochemistry with quantitative image analysis. Plaques from the pravastatin group had less... (More)
Background--The clinical benefits of lipid lowering with statins are attributed to changes in plaque composition leading to lesion stability, but supporting clinical data from human studies are lacking. Therefore, we investigated the effect of 3 months of pravastatin treatment on composition of human carotid plaques removed during carotid endarterectomy. Methods and Results--Consecutive patients with symptomatic carotid artery stenosis received 40 mg/d pravastatin (n=11) or no lipid-lowering therapy (n=13; control subjects) for 3 months before scheduled carotid endarterectomy. Carotid Plaque composition was assessed with special stains and immunocytochemistry with quantitative image analysis. Plaques from the pravastatin group had less lipid by oil red O staining (8.2 +/-8.4% versus 23.9 +/- 21.1% of the plaque area, P<0.05), less oxidized LDL immunoreactivity (13.3<plus/minus>3.6% versus 22.0 +/-6.5%, P<0.001), fewer macrophages (15.0<plus/minus>10.2% versus 25.3 +/- 12.5%, P<0.05), fewer T cells (11.2<plus/minus>9.3% versus 24.3 +/- 13.4%, P<0.05), less matrix metalloproteinase 2 (MMP-2) immunoreactivity (3.6<plus/minus>3.9% versus 8.4 +/-5.3%, P<0.05), greater tissue inhibitor of metalloproteinase 1 (TIMP-1) immunoreactivity (9.0<plus/minus>6.2% versus 3.1 +/-3.9%, P<0.05), and a higher collagen content by Sirius red staining (12.4<plus/minus>3.1% versus 7.5 +/-3.5%, P<0.005), Cell death by TUNEL staining was reduced in the pravastatin group (17.7<plus/minus>7.8% versus 32.0 +/- 12.6%, P<0.05). Conclusions--Pravastatin decreased lipids, lipid oxidation, inflammation, MMP-2, and cell death and increased TIMP-1 and collagen content in human carotid plaques, confirming its plaque-stabilizing effect in humans. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
pravastatin, plaque, inflammation
in
Circulation
volume
103
issue
7
pages
926 - 933
publisher
Lippincott Williams and Wilkins
external identifiers
  • wos:000167562000004
  • scopus:0035916233
ISSN
1524-4539
language
English
LU publication?
yes
id
11f6b4c6-8f31-4c66-926f-a13122935b6a (old id 1119425)
alternative location
http://circ.ahajournals.org/cgi/content/full/103/7/926
date added to LUP
2008-06-26 09:31:55
date last changed
2018-04-15 04:09:13
@article{11f6b4c6-8f31-4c66-926f-a13122935b6a,
  abstract     = {Background--The clinical benefits of lipid lowering with statins are attributed to changes in plaque composition leading to lesion stability, but supporting clinical data from human studies are lacking. Therefore, we investigated the effect of 3 months of pravastatin treatment on composition of human carotid plaques removed during carotid endarterectomy. Methods and Results--Consecutive patients with symptomatic carotid artery stenosis received 40 mg/d pravastatin (n=11) or no lipid-lowering therapy (n=13; control subjects) for 3 months before scheduled carotid endarterectomy. Carotid Plaque composition was assessed with special stains and immunocytochemistry with quantitative image analysis. Plaques from the pravastatin group had less lipid by oil red O staining (8.2 +/-8.4% versus 23.9 +/- 21.1% of the plaque area, P&lt;0.05), less oxidized LDL immunoreactivity (13.3&lt;plus/minus&gt;3.6% versus 22.0 +/-6.5%, P&lt;0.001), fewer macrophages (15.0&lt;plus/minus&gt;10.2% versus 25.3 +/- 12.5%, P&lt;0.05), fewer T cells (11.2&lt;plus/minus&gt;9.3% versus 24.3 +/- 13.4%, P&lt;0.05), less matrix metalloproteinase 2 (MMP-2) immunoreactivity (3.6&lt;plus/minus&gt;3.9% versus 8.4 +/-5.3%, P&lt;0.05), greater tissue inhibitor of metalloproteinase 1 (TIMP-1) immunoreactivity (9.0&lt;plus/minus&gt;6.2% versus 3.1 +/-3.9%, P&lt;0.05), and a higher collagen content by Sirius red staining (12.4&lt;plus/minus&gt;3.1% versus 7.5 +/-3.5%, P&lt;0.005), Cell death by TUNEL staining was reduced in the pravastatin group (17.7&lt;plus/minus&gt;7.8% versus 32.0 +/- 12.6%, P&lt;0.05). Conclusions--Pravastatin decreased lipids, lipid oxidation, inflammation, MMP-2, and cell death and increased TIMP-1 and collagen content in human carotid plaques, confirming its plaque-stabilizing effect in humans.},
  author       = {Crisby, Milita and Nordin Fredrikson, Gunilla and Shah, Prediman K. and Yano, Juliana and Zhu, Jenny and Nilsson, Jan},
  issn         = {1524-4539},
  keyword      = {pravastatin,plaque,inflammation},
  language     = {eng},
  number       = {7},
  pages        = {926--933},
  publisher    = {Lippincott Williams and Wilkins},
  series       = {Circulation},
  title        = {Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques - Implications for plaque stabilization},
  volume       = {103},
  year         = {2001},
}