Rosiglitazone attenuates atherosclerosis and increases high-density lipoprotein function in atherosclerotic rabbits

Li,Chen; Tu,Yan; Liu,Ting-Rong; Guo,Zhi-Gang; Xie,Di; Zhong,Jian-Kai; Fan,Yong-Zhen; Lai,Wen-Yan

doi:10.3892/ijmm.2015.2072

Rosiglitazone attenuates atherosclerosis and increases high-density lipoprotein function in atherosclerotic rabbits

Authors:
- Chen Li
- Yan Tu
- Ting-Rong Liu
- Zhi-Gang Guo
- Di Xie
- Jian-Kai Zhong
- Yong-Zhen Fan
- Wen-Yan Lai
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Affiliations: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: January 19, 2015 https://doi.org/10.3892/ijmm.2015.2072
Pages: 715-723
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Rosiglitazone has been found to have anti-atherogenic effects and to increase serum high-density lipoprotein (HDL) cholesterol (HDL-C) levels. However, in vivo studies investigating the regulation of adenosine triphosphate-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI) by rosiglitazone are limited. Moreover, the effects of rosiglitazone on the function and levels of HDL are unclear. In the present study, we investigated the effects of rosiglitazone on HDL function and its mechanisms of action in atherosclerotic rabbits. Our results revealed that rosiglitazone induced a significant increase in serum HDL-C levels, paraoxonase 1 (PON1) activity, [3H]cholesterol efflux rates, and the expression of ABCA1 and SR-BI in hepatocytes and peritoneal macrophages. The expression of ABCA1 was also increased in aortic lesions. Rosiglitazone markedly reduced serum myeloperoxidase (MPO) activity, aortic intima-media thickness (IMT) and the percentage of plaque area in the aorta. It can thus be concluded that in atherosclerotic rabbits, rosigitazone increases the levels of HDL-C and hinders atherosclerosis. Thus, it improves HDL quality and function, as well as the HDL-induced cholesterol efflux, exerting anti-inflammatory and antioxidant effects.

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1	Rader DJ: Molecular regulation of HDL metabolism and function: implications for novel therapies. J Clin Invest. 116:3090–3100. 2006. View Article : Google Scholar : PubMed/NCBI
2	Frikke-Schmidt R, Nordestgaard BG, Stene MC, et al: Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease. JAMA. 299:2524–2532. 2008. View Article : Google Scholar : PubMed/NCBI
3	Roberts CK, Ng C, Hama S, Eliseo AJ and Barnard RJ: Effect of a short-term diet and exercise intervention on inflammatory/anti-inflammatory properties of HDL in overweight/obese men with cardiovascular risk factors. J Appl Physiol (1985). 101:1727–1732. 2006. View Article : Google Scholar
4	Dodani S, Grice DG and Joshi S: Is HDL function as important as HDL quantity in the coronary artery disease risk assessment? J Clin Lipidol. 3:70–77. 2009. View Article : Google Scholar : PubMed/NCBI
5	Assmann G and Gotto AM Jr: HDL cholesterol and protective factors in atherosclerosis. Circulation. 109:III8–III14. 2004. View Article : Google Scholar : PubMed/NCBI
6	Singh IM, Shishehbor MH and Ansell BJ: High-density lipoprotein as a therapeutic target: a systematic review. JAMA. 298:786–798. 2007. View Article : Google Scholar : PubMed/NCBI
7	Brewer HB Jr: High-density lipoproteins: a new potential therapeutic target for the prevention of cardiovascular disease. Arterioscler Thromb Vasc Biol. 24:387–391. 2004. View Article : Google Scholar : PubMed/NCBI
8	Attie AD, Kastelein JP and Hayden MR: Pivotal role of ABCA1 in reverse cholesterol transport influencing HDL levels and susceptibility to atherosclerosis. J Lipid Res. 42:1717–1726. 2001.PubMed/NCBI
9	Zannis VI, Chroni A and Krieger M: Role of apoA-I, ABCA1, LCAT, and SR-BI in the biogenesis of HDL. J Mol Med (Berl). 84:276–294. 2006. View Article : Google Scholar
10	Trigatti BL, Krieger M and Rigotti A: Influence of the HDL receptor SR-BI on lipoprotein metabolism and atherosclerosis. Arterioscler Thromb Vasc Biol. 23:1732–1738. 2003. View Article : Google Scholar : PubMed/NCBI
11	Ji Y, Wang N, Ramakrishnan R, et al: Hepatic scavenger receptor BI promotes rapid clearance of high density lipoprotein free cholesterol and its transport into bile. J Biol Chem. 274:33398–33402. 1999. View Article : Google Scholar : PubMed/NCBI
12	Ueda Y, Royer L, Gong E, et al: Lower plasma levels and accelerated clearance of high density lipoprotein (HDL) and non-HDL cholesterol in scavenger receptor class B type I transgenic mice. J Biol Chem. 274:7165–7171. 1999. View Article : Google Scholar : PubMed/NCBI
13	Nolan JJ, Ludvik B, Beerdsen P, Joyce M and Olefsky J: Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N Engl J Med. 331:1188–1193. 1994. View Article : Google Scholar : PubMed/NCBI
14	Choi D, Kim SK, Choi SH, et al: Preventative effects of rosiglitazone on restenosis after coronary stent implantation in patients with type 2 diabetes. Diabetes Care. 27:2654–2660. 2004. View Article : Google Scholar : PubMed/NCBI
15	Gerstein HC, Ratner RE, Cannon CP, et al: Effect of rosiglitazone on progression of coronary atherosclerosis in patients with type 2 diabetes mellitus and coronary artery disease: the assessment on the prevention of progression by rosiglitazone on atherosclerosis in diabetes patients with cardiovascular history trial. Circulation. 121:1176–1187. 2010. View Article : Google Scholar : PubMed/NCBI
16	Kelly AS and Bank AJ: The cardiovascular effects of the thiazolidinediones: a review of the clinical data. J Diabetes Complications. 21:326–334. 2007. View Article : Google Scholar : PubMed/NCBI
17	Sidhu JS, Kaposzta Z, Markus HS and Kaski JC: Effect of rosiglitazone on common carotid intima-media thickness progression in coronary artery disease patients without diabetes mellitus. Arterioscler Thromb Vasc Biol. 24:930–934. 2004. View Article : Google Scholar : PubMed/NCBI
18	Marx N, Duez H, Fruchart JC and Staels B: Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells. Circ Res. 94:1168–1178. 2004. View Article : Google Scholar : PubMed/NCBI
19	Malerød L, Sporstol M, Juvet LK, Mousavi A, Gjøen T and Berg T: Hepatic scavenger receptor class B, type I is stimulated by peroxisome proliferator-activated receptor gamma and hepatocyte nuclear factor 4alpha. Biochem Biophys Res Commun. 305:557–565. 2003. View Article : Google Scholar : PubMed/NCBI
20	Llaverias G, Rebollo A, Pou J, et al: Effects of rosiglitazone and atorvastatin on the expression of genes that control cholesterol homeostasis in differentiating monocytes. Biochem Pharmacol. 71:605–614. 2006. View Article : Google Scholar : PubMed/NCBI
21	Carreon-Torres E, Rendon-Sauer K, Monter-Garrido M, et al: Rosiglitazone modifies HDL structure and increases HDL-apoAI synthesis and catabolic rates. Clin Chim Acta. 401:37–41. 2009. View Article : Google Scholar
22	Fan JG, Chen LH, Xu ZJ and Zeng MD: Overexpression of hepatic plasminogen activator inhibitor type 1 mRNA in rabbits with fatty liver. World J Gastroenterol. 7:710–712. 2001.
23	Zhao SP, Yang J, Li J, Dong SZ and Wu ZH: Effect of niacin on LXRalpha and PPARgamma expression and HDL-induced cholesterol efflux in adipocytes of hypercholesterolemic rabbits. Int J Cardiol. 124:172–178. 2008. View Article : Google Scholar
24	Troutt JS, Alborn WE, Mosior MK, et al: An apolipoprotein A-I mimetic dose-dependently increases the formation of prebeta1 HDL in human plasma. J Lipid Res. 49:581–587. 2008. View Article : Google Scholar
25	Havel RJ, Eder HA and Bragdon JH: The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 34:1345–1353. 1955. View Article : Google Scholar : PubMed/NCBI
26	Pirillo A, Norata GD, Zanelli T and Catapano AL: Overexpression of inducible heat shock protein 70 in Cos-1 cells fails to protect from cytotoxicity of oxidized ldls. Arterioscler Thromb Vasc Biol. 21:348–354. 2001. View Article : Google Scholar : PubMed/NCBI
27	Pirillo A, Uboldi P, Kuhn H and Catapano AL: 15-Lipoxygenase-mediated modification of high-density lipoproteins impairs SR-BI- and ABCA1-dependent cholesterol efflux from macrophages. Biochim Biophys Acta. 1761:292–300. 2006. View Article : Google Scholar : PubMed/NCBI
28	Zhong JK, Guo ZG, Li C, et al: Probucol alleviates atherosclerosis and improves high density lipoprotein function. Lipids Health Dis. 10(210): 2011
29	Speidl WS, Cimmino G, Ibanez B, et al: Recombinant apolipoprotein A-I Milano rapidly reverses aortic valve stenosis and decreases leaflet inflammation in an experimental rabbit model. Eur Heart J. 31:2049–2057. 2010. View Article : Google Scholar : PubMed/NCBI
30	Beltowski J, Jamroz-Wisniewska A, Borkowska E and Wojcicka G: Differential effect of antioxidant treatment on plasma and tissue paraoxonase activity in hyperleptinemic rats. Pharmacol Res. 51:523–532. 2005. View Article : Google Scholar : PubMed/NCBI
31	Fan J and Watanabe T: Transgenic rabbits as therapeutic protein bioreactors and human disease models. Pharmacol Ther. 99:261–282. 2003. View Article : Google Scholar : PubMed/NCBI
32	Ansell BJ, Fonarow GC and Fogelman AM: High-density lipoprotein: is it always atheroprotective? Curr Atheroscler Rep. 8:405–411. 2006. View Article : Google Scholar : PubMed/NCBI
33	Szapary PO, Bloedon LT, Samaha FF, et al: Effects of pioglitazone on lipoproteins, inflammatory markers, and adipokines in nondiabetic patients with metabolic syndrome. Arterioscler Thromb Vasc Biol. 26:182–188. 2006. View Article : Google Scholar
34	Chiesa G and Sirtori CR: Apolipoprotein A-I(Milano): current perspectives. Curr Opin Lipidol. 14:159–163. 2003. View Article : Google Scholar : PubMed/NCBI
35	Hiroshi N: Latest insights into high-density lipoprotein functions. Endocrinologist. 19:179–186. 2009. View Article : Google Scholar
36	Fogelman AM: When good cholesterol goes bad. Nat Med. 10:902–903. 2004. View Article : Google Scholar : PubMed/NCBI
37	von Eckardstein A, Nofer JR and Assmann G: High density lipoproteins and arteriosclerosis. Role of cholesterol efflux and reverse cholesterol transport. Arterioscler Thromb Vasc Biol. 21:13–27. 2001. View Article : Google Scholar : PubMed/NCBI
38	Calpe-Berdiel L, Rotllan N, Palomer X, Ribas V, Blanco-Vaca F and Escola-Gil JC: Direct evidence in vivo of impaired macrophage-specific reverse cholesterol transport in ATP-binding cassette transporter A1-deficient mice. Biochim Biophys Acta. 1738:6–9. 2005. View Article : Google Scholar
39	Kozarsky KF, Donahee MH, Rigotti A, Iqbal SN, Edelman ER and Krieger M: Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels. Nature. 387:414–417. 1997. View Article : Google Scholar : PubMed/NCBI
40	Wang N, Arai T, Ji Y, Rinninger F and Tall AR: Liver-specific overexpression of scavenger receptor BI decreases levels of very low density lipoprotein ApoB, low density lipoprotein ApoB, and high density lipoprotein in transgenic mice. J Biol Chem. 273:32920–32926. 1998. View Article : Google Scholar : PubMed/NCBI
41	Kozarsky KF, Donahee MH, Glick JM, Krieger M and Rader DJ: Gene transfer and hepatic overexpression of the HDL receptor SR-BI reduces atherosclerosis in the cholesterol-fed LDL receptor-deficient mouse. Arterioscler Thromb Vasc Biol. 20:721–727. 2000. View Article : Google Scholar : PubMed/NCBI
42	Varban ML, Rinninger F, Wang N, et al: Targeted mutation reveals a central role for SR-BI in hepatic selective uptake of high density lipoprotein cholesterol. Proc Natl Acad Sci USA. 95:4619–4624. 1998. View Article : Google Scholar : PubMed/NCBI
43	Braun A, Trigatti BL, Post MJ, et al: Loss of SR-BI expression leads to the early onset of occlusive atherosclerotic coronary artery disease, spontaneous myocardial infarctions, severe cardiac dysfunction, and premature death in apolipoprotein E-deficient mice. Circ Res. 90:270–276. 2002. View Article : Google Scholar : PubMed/NCBI
44	Zhang Y, Da Silva JR, Reilly M, Billheimer JT, Rothblat GH and Rader DJ: Hepatic expression of scavenger receptor class B type I (SR-BI) is a positive regulator of macrophage reverse cholesterol transport in vivo. J Clin Invest. 115:2870–2874. 2005. View Article : Google Scholar : PubMed/NCBI
45	Chawla A, Boisvert WA, Lee CH, et al: A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell. 7:161–171. 2001. View Article : Google Scholar : PubMed/NCBI
46	Chinetti G, Lestavel S, Bocher V, et al: PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med. 7:53–58. 2001. View Article : Google Scholar : PubMed/NCBI
47	Wang N, Ranalletta M, Matsuura F, Peng F and Tall AR: LXR-induced redistribution of ABCG1 to plasma membrane in macrophages enhances cholesterol mass efflux to HDL. Arterioscler Thromb Vasc Biol. 26:1310–1316. 2006. View Article : Google Scholar : PubMed/NCBI
48	Sviridov D, Mukhamedova N, Remaley AT, Chin-Dusting J and Nestel P: Antiatherogenic functionality of high density lipoprotein: how much versus how good. J Atheroscler Thromb. 15:52–62. 2008. View Article : Google Scholar : PubMed/NCBI
49	Tward A, Xia YR, Wang XP, et al: Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation. 106:484–490. 2002. View Article : Google Scholar : PubMed/NCBI
50	Bhattacharyya T, Nicholls SJ, Topol EJ, et al: Relationship of paraoxonase 1 (PON1) gene polymorphisms and functional activity with systemic oxidative stress and cardiovascular risk. JAMA. 299:1265–1276. 2008. View Article : Google Scholar : PubMed/NCBI
51	Holvoet P: Oxidized LDL and coronary heart disease. Acta Cardiol. 59:479–484. 2004. View Article : Google Scholar : PubMed/NCBI
52	Shao B, Oda MN, Oram JF and Heinecke JW: Myeloperoxidase: an inflammatory enzyme for generating dysfunctional high density lipoprotein. Curr Opin Cardiol. 21:322–328. 2006. View Article : Google Scholar : PubMed/NCBI