Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques - Implications for plaque stabilization
M. Crisby et al., Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques - Implications for plaque stabilization, CIRCULATION, 103(7), 2001, pp. 926-933
Citations number
43
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background--The clinical benefits of lipid lowering with statins are attrib
uted to changes in plaque composition leading to lesion stability, but supp
orting clinical data from human studies are lacking. Therefore, we investig
ated the effect of 3 months of pravastatin treatment on composition of huma
n carotid plaques removed during carotid endarterectomy.
Methods and Results--Consecutive patients with symptomatic carotid artery s
tenosis 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 immunocyt
ochemistry with quantitative image analysis. Plaques from the pravastatin g
roup 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<plu
s/minus>3.6% versus 22.0 +/-6.5%, P<0.001), fewer macrophages (15.0<plus/mi
nus>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 S
irius 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/mi
nus>7.8% versus 32.0 +/- 12.6%, P<0.05).
Conclusions--Pravastatin decreased lipids, lipid oxidation, inflammation, M
MP-2, and cell death and increased TIMP-1 and collagen content in human car
otid plaques, confirming its plaque-stabilizing effect in humans.