Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques - Implications for plaque stabilization
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1119425
- author
- Crisby, Milita ; Nordin Fredrikson, Gunilla LU ; Shah, Prediman K. ; Yano, Juliana ; Zhu, Jenny and Nilsson, Jan LU
- organization
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- pravastatin, plaque, inflammation
- in
- Circulation
- volume
- 103
- issue
- 7
- pages
- 926 - 933
- publisher
- Lippincott Williams & 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
- 2016-04-01 16:00:44
- date last changed
- 2022-04-22 18:54:02
@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<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.}}, author = {{Crisby, Milita and Nordin Fredrikson, Gunilla and Shah, Prediman K. and Yano, Juliana and Zhu, Jenny and Nilsson, Jan}}, issn = {{1524-4539}}, keywords = {{pravastatin; plaque; inflammation}}, language = {{eng}}, number = {{7}}, pages = {{926--933}}, publisher = {{Lippincott Williams & 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}}, url = {{http://circ.ahajournals.org/cgi/content/full/103/7/926}}, volume = {{103}}, year = {{2001}}, }