Effect of cholesterol re-supplementation and atorvastatin on plaque composition in the thoracic aorta of New Zealand white rabbits.
Apoptosis
Atherosclerosis
Atorvastatin
Hypercholesterolemic rabbits
Macrophage
Re-supplementation
Journal
BMC cardiovascular disorders
ISSN: 1471-2261
Titre abrégé: BMC Cardiovasc Disord
Pays: England
ID NLM: 100968539
Informations de publication
Date de publication:
17 09 2020
17 09 2020
Historique:
received:
09
07
2020
accepted:
10
09
2020
entrez:
18
9
2020
pubmed:
19
9
2020
medline:
26
1
2021
Statut:
epublish
Résumé
Effects of re-supplementation of a cholesterol-enriched diet (CEDrs) on size, cholesterol content and morphology of already existing plaques are not known to date. A group of rabbits received standard chow (SC) for 6 weeks ("negative control"; for plasma lipid measurements only). Group I-IV received 2% CED (induction) for 6 weeks; thereafter, groups II-IV have been fed a SC (= cholesterol withdrawal) for 68 weeks. Afterwards, feeding of groups II-IV was continued as follows: Group II - 10 weeks SC, group III - 4 weeks 0.5% CED (~re-supplementation), afterwards 6 weeks SC (~withdrawal again); group IV - 4 weeks 0.5% CED (re-supplementation) + atorvastatin (2.5 mg/kg body weight/day), afterwards 6 weeks SC (~withdrawal again) + atorvastatin. Plasma lipids, but also plaque size, morphology and cholesterol contents of thoracic aortas were quantified. After CEDrs, plasma cholesterol levels were increased. However, after withdrawal of CEDrs, plasma cholesterol levels decreased, whereas the cholesterol content of the thoracic aorta was increased in comparison with the group without CEDrs. Plaque size remained unaffected. Atorvastatin application did not change plasma cholesterol level, cholesterol content of the thoracic aorta and plaque size in comparison with the group without drug treatment. However, atorvastatin treatment increased the density of macrophages (MΦ) compared with the group without treatment, with a significant correlation between densities of MΦ (Mac-1 In rabbits with already existing plaques, CEDrs affects plaque morphology and cellular composition, but not plaque size. Despite missing effects on plasma cholesterol levels, cholesterol content of the thoracic aorta and size of already existing atherosclerotic plaques, atorvastatin treatment transforms the already existing lesions to a more active form, which may accelerate the remodelling to a more stable plaque.
Sections du résumé
BACKGROUND
Effects of re-supplementation of a cholesterol-enriched diet (CEDrs) on size, cholesterol content and morphology of already existing plaques are not known to date.
METHODS
A group of rabbits received standard chow (SC) for 6 weeks ("negative control"; for plasma lipid measurements only). Group I-IV received 2% CED (induction) for 6 weeks; thereafter, groups II-IV have been fed a SC (= cholesterol withdrawal) for 68 weeks. Afterwards, feeding of groups II-IV was continued as follows: Group II - 10 weeks SC, group III - 4 weeks 0.5% CED (~re-supplementation), afterwards 6 weeks SC (~withdrawal again); group IV - 4 weeks 0.5% CED (re-supplementation) + atorvastatin (2.5 mg/kg body weight/day), afterwards 6 weeks SC (~withdrawal again) + atorvastatin. Plasma lipids, but also plaque size, morphology and cholesterol contents of thoracic aortas were quantified.
RESULTS
After CEDrs, plasma cholesterol levels were increased. However, after withdrawal of CEDrs, plasma cholesterol levels decreased, whereas the cholesterol content of the thoracic aorta was increased in comparison with the group without CEDrs. Plaque size remained unaffected. Atorvastatin application did not change plasma cholesterol level, cholesterol content of the thoracic aorta and plaque size in comparison with the group without drug treatment. However, atorvastatin treatment increased the density of macrophages (MΦ) compared with the group without treatment, with a significant correlation between densities of MΦ (Mac-1
CONCLUSIONS
In rabbits with already existing plaques, CEDrs affects plaque morphology and cellular composition, but not plaque size. Despite missing effects on plasma cholesterol levels, cholesterol content of the thoracic aorta and size of already existing atherosclerotic plaques, atorvastatin treatment transforms the already existing lesions to a more active form, which may accelerate the remodelling to a more stable plaque.
Identifiants
pubmed: 32942987
doi: 10.1186/s12872-020-01703-x
pii: 10.1186/s12872-020-01703-x
pmc: PMC7499881
doi:
Substances chimiques
Cholesterol, Dietary
0
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Atorvastatin
A0JWA85V8F
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
420Références
Eur Heart J. 2020 Jun 21;41(24):2313-2330
pubmed: 32052833
J Leukoc Biol. 1997 Dec;62(6):719-25
pubmed: 9400812
Am J Physiol Heart Circ Physiol. 2013 Jun 15;304(12):H1743-51
pubmed: 23585134
J Nucl Med. 2005 Dec;46(12):2051-6
pubmed: 16330569
J Am Coll Cardiol. 2018 Oct 30;72(18):2166-2180
pubmed: 30360826
Atherosclerosis. 2010 Jun;210(2):407-13
pubmed: 20138623
Sci Adv. 2015 Apr;1(3):
pubmed: 26295063
Lab Invest. 1985 Jul;53(1):80-90
pubmed: 3892159
Arterioscler Thromb Vasc Biol. 2020 Jan;40(1):20-33
pubmed: 31722535
Atherosclerosis. 2008 Mar;197(1):34-42
pubmed: 17904562
Heart. 2017 Nov;103(21):1670-1679
pubmed: 28596304
Exp Mol Pathol. 2017 Feb;102(1):138-145
pubmed: 28108216
Eur Heart J. 2020 Jan 1;41(1):111-188
pubmed: 31504418
Circ Res. 2019 Jan 18;124(2):315-327
pubmed: 30653442
BMC Public Health. 2011 Jun 25;11:497
pubmed: 21702967
Z Gerontol. 1990 May-Jun;23(3):140-2
pubmed: 2392870
Pharmacol Ther. 2015 Feb;146:104-19
pubmed: 25277507
Nat Med. 1999 Mar;5(3):335-9
pubmed: 10086392
Nat Med. 2018 Jun;24(6):711-720
pubmed: 29867229
Atherosclerosis. 2005 Feb;178(2):287-94
pubmed: 15694936
Arterioscler Thromb Vasc Biol. 2014 Nov;34(11):2465-72
pubmed: 25212234
J Am Coll Cardiol. 2010 Jun 15;55(24):2736-42
pubmed: 20538166
Circulation. 2018 Jul 10;138(2):131-140
pubmed: 29530884
Atherosclerosis. 2016 May;248:117-22
pubmed: 27015246
BMC Med. 2015 Oct 08;13:260
pubmed: 26449405
Circulation. 2001 Jul 17;104(3):365-72
pubmed: 11457759
Front Pharmacol. 2019 Apr 04;10:306
pubmed: 31019462
Proc Soc Exp Biol Med. 1957 Jul;95(3):586-8
pubmed: 13453516
N Engl J Med. 1990 Nov 8;323(19):1289-98
pubmed: 2215615
Eur Heart J Cardiovasc Imaging. 2014 Apr;15(4):380-8
pubmed: 24448227
Nanoscale. 2020 May 7;12(17):9541-9556
pubmed: 32314997
Medicine (Baltimore). 2018 Aug;97(31):e11718
pubmed: 30075578
J Am Coll Cardiol. 1998 Dec;32(7):2057-64
pubmed: 9857893
Heart. 2003 Apr;89(4):451-8
pubmed: 12639883
Pathol Oncol Res. 2004;10(3):159-65
pubmed: 15448752
J Am Coll Cardiol. 2018 Oct 30;72(18):2181-2197
pubmed: 30360827
Eur J Pharmacol. 2014 Nov 15;743:31-6
pubmed: 25261034
Sci Rep. 2017 May 19;7(1):2169
pubmed: 28526884
Biofactors. 2020 May;46(3):367-380
pubmed: 31999032
Atherosclerosis. 2018 Feb;269:219-228
pubmed: 29407597
Eur J Pharmacol. 2017 Dec 5;816:3-13
pubmed: 28483459
Cell Tissue Res. 2005 Dec;322(3):425-35
pubmed: 16133150
Atherosclerosis. 2016 Nov;254:78-84
pubmed: 27710808
Atherosclerosis. 1999 May;144(1):33-9
pubmed: 10381275
Mediators Inflamm. 2015;2015:718329
pubmed: 25960621
J Biol Chem. 1951 Aug;191(2):833-41
pubmed: 14861228
Cardiovasc Res. 2002 Oct;56(1):135-44
pubmed: 12237174
J Am Coll Cardiol. 2015 Apr 7;65(13):1273-1282
pubmed: 25835438
Int J Cardiol. 2017 Jan 15;227:644-649
pubmed: 27810295
Sci Rep. 2015 Oct 22;5:15524
pubmed: 26490319
Cell Death Differ. 2004 Jul;11 Suppl 1:S12-6
pubmed: 15143347
Ann N Y Acad Sci. 1985;454:101-14
pubmed: 3865603