Impact of short-term administration of high-density lipoproteins and atorvastatin on atherosclerosis in rabbits.
OBJECTIVE
This study investigates effects of short-term administration of high-density lipoproteins (HDL) and a statin on atherosclerosis in cholesterol-fed rabbits. Effects of HDL apolipoprotein and phospholipid composition have also been investigated.


RESULTS
Aortic atherosclerosis was established over 17 weeks in 46 rabbits by balloon denudation and cholesterol feeding. During the past 5 days of the cholesterol-feeding period, animals received: (1) no treatment; (2) oral atorvastatin 5 mg/kg on each of the 5 days; or (3) infusions of HDL (8 mg/kg apolipoprotein A-I) on days 1 and 3 of the treatment phase. After euthanization, lesion size and composition were assessed by histological and immunohistochemical analysis. HDL (but not atorvastatin) reduced lesion size by 36% (P<0.05). The ratio of smooth muscle cells to macrophages in the lesions increased 2.6-fold in animals infused with HDL (P<0.05) and 4-fold in those receiving atorvastatin (P<0.01). HDL and atorvastatin reduced matrix metalloproteinase (MMP)-9 expression by 42% (P<0.05) and 45% (P<0.03), respectively. HDL increased thrombomodulin expression 2-fold (P<0.03). The beneficial effects on lesion area and plaque cellular composition were influenced by HDL phospholipid and apolipoprotein composition.


CONCLUSIONS
Infusing small amounts of HDL rapidly reduces lesion size and is comparable to atorvastatin in promoting a stable plaque phenotype.
Nicholls
Stephen J
SJ
The Heart Research Institute, Sydney, Australia.
Cutri
Belinda
B
Worthley
Stephen G
SG
Kee
Patrick
P
Rye
Kerry-Anne
KA
Bao
Shisan
S
Barter
Philip J
PJ
D000818:Animals; D001018:Aortic Diseases / Q000188:drug therapy / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology*; D000069059:Atorvastatin; D002791:Cholesterol, Dietary / Q000097:blood / Q000494:pharmacology; D004359:Drug Therapy, Combination; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000097:blood / Q000494:pharmacology*; D008297:Male; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits
D002791:Cholesterol, Dietary; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008075:Lipoproteins, HDL; D011758:Pyrroles; D000069059:Atorvastatin