on September 1, 2005
Published online before print September 1, 2005, doi: 10.1161/01.ATV.0000184760.95957.d6
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on May 17, 2005
Accepted on July 25, 2005
Impact of Short-Term Administration of High-Density Lipoproteins and Atorvastatin on Atherosclerosis in Rabbits
Stephen J. Nicholls ;
From The Heart Research Institute, Sydney, Australia Department of Medicine, University of Adelaide, Adelaide, Australia Cardiovascular Investigation Unit, Royal Adelaide Hospital, Adelaide, Australia Department of Medicine, University of Sydney, Sydney, Australia Department of Medicine, University of Melbourne, Melbourne, Australia Department of Pathology, University of Sydney, Sydney, Australia.
* To whom correspondence should be addressed. E-mail: p.barter{at}hri.org.au.
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.
Methods and 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.
Conclusion--Infusing small amounts of HDL rapidly reduces lesion size and is comparable to atorvastatin in promoting a stable plaque phenotype.
Key words: atherosclerosis • high-density lipoprotein • inflammation • lipoproteins • plaque stabilization
This article has been cited by other articles:
 |
|
 |
|
  K. J.E. Sattler, J. Herrmann, S. Yun, N. Lehmann, Z. Wang, G. Heusch, S. Sack, R. Erbel, and B. Levkau High high-density lipoprotein-cholesterol reduces risk and extent of percutaneous coronary intervention-related myocardial infarction and improves long-term outcome in patients undergoing elective percutaneous coronary intervention Eur. Heart J., August 1, 2009; 30(15): 1894 - 1902. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sattler and B. Levkau Sphingosine-1-phosphate as a mediator of high-density lipoprotein effects in cardiovascular protection Cardiovasc Res, May 1, 2009; 82(2): 201 - 211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. El Harchaoui, B. J. Arsenault, R. Franssen, J.-P. Despres, G. K. Hovingh, E. S.G. Stroes, J. D. Otvos, N. J. Wareham, J. J.P. Kastelein, K.-T. Khaw, et al. High-Density Lipoprotein Particle Size and Concentration and Coronary Risk Ann Intern Med, January 20, 2009; 150(2): 84 - 93. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Nicholls, E. M. Tuzcu, D. M. Brennan, J.-C. Tardif, and S. E. Nissen Cholesteryl Ester Transfer Protein Inhibition, High-Density Lipoprotein Raising, and Progression of Coronary Atherosclerosis: Insights From ILLUSTRATE (Investigation of Lipid Level Management Using Coronary Ultrasound to Assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation) Circulation, December 9, 2008; 118(24): 2506 - 2514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Shaw, A. Bobik, A. Murphy, P. Kanellakis, P. Blombery, N. Mukhamedova, K. Woollard, S. Lyon, D. Sviridov, and A. M. Dart Infusion of Reconstituted High-Density Lipoprotein Leads to Acute Changes in Human Atherosclerotic Plaque Circ. Res., November 7, 2008; 103(10): 1084 - 1091. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D J Hausenloy and D M Yellon Targeting residual cardiovascular risk: raising high-density lipoprotein cholesterol levels Postgrad. Med. J., November 1, 2008; 84(997): 590 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. deGoma, R. L. deGoma, and D. J. Rader Beyond high-density lipoprotein cholesterol levels evaluating high-density lipoprotein function as influenced by novel therapeutic approaches. J. Am. Coll. Cardiol., June 10, 2008; 51(23): 2199 - 2211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D J Hausenloy and D M Yellon Targeting residual cardiovascular risk: raising high-density lipoprotein cholesterol levels Heart, June 1, 2008; 94(6): 706 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, S. Bao, D. Lai, R. W. Rapkins, and M. C. Gillies Intravitreal Triamcinolone Acetonide Inhibits Breakdown of the Blood-Retinal Barrier Through Differential Regulation of VEGF-A and Its Receptors in Early Diabetic Rat Retinas Diabetes, April 1, 2008; 57(4): 1026 - 1033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ibanez, G. Vilahur, G. Cimmino, W. S. Speidl, A. Pinero, B. G. Choi, M. U. Zafar, C. G. Santos-Gallego, B. Krause, L. Badimon, et al. Rapid change in plaque size, composition, and molecular footprint after recombinant apolipoprotein A-I Milano (ETC-216) administration: magnetic resonance imaging study in an experimental model of atherosclerosis. J. Am. Coll. Cardiol., March 18, 2008; 51(11): 1104 - 1109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kontush and M. J. Chapman Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis Pharmacol. Rev., September 1, 2006; 58(3): 342 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mineo, H. Deguchi, J. H. Griffin, and P. W. Shaul Endothelial and Antithrombotic Actions of HDL Circ. Res., June 9, 2006; 98(11): 1352 - 1364. [Abstract] [Full Text] [PDF]
|
|