Skip to main content
SpringerLink
Log in

Elastic aortic wrap reduced aortic stiffness by partially alleviating the impairment of cholesterol efflux capacity in pigs

  • Research Article
  • Published:
Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

Abstract

Purpose

Metabolic syndrome patients exhibit impaired cholesterol efflux capacity. Previous studies have shown a positive association between aortic stiffness and metabolic syndrome. However, it is unknown whether cholesterol efflux capacity participates in the process of aortic stiffness. This study sought to determine the effect of metabolic syndrome on aortic stiffening, and to investigate the effectiveness of aortic wraps on aortic compliance and the underlying mechanisms.

Methods

In a swine model of metabolic syndrome, we compared the cholesterol efflux capacity and aortic compliance responding to diet modifications and aortic wrap applications.

Results

Metabolic syndrome induced by high cholesterol diet significantly decreased cholesterol efflux capacity and aortic compliance. Elastic aortic wrap application increased aortic compliance and partially restored cholesterol efflux capacity via ATP binding cassette transporter A1 (ABCA1) pathway.

Conclusions

Cholesterol efflux plays a role in aortic stiffening. Elastic aortic wrap application could be a potential treatment for aortic stiffness related to metabolic syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

Apo:

Apolipoprotein (Apo)

ABCA1:

ATP binding cassette transporter A1

ABCG1:

ATP binding cassette transporter G1

EF:

Ejection fraction

LVEDV:

Left ventricular end diastolic volume

LVESV:

Left ventricular end systolic volume

PSEM:

Pressure-strain elastic modulus

SR-BI:

Scavenger receptor class B, type I

TEE:

Transesophageal echocardiography

References

  1. Ballantyne CM, Hoogeveen RC, McNeill AM, Heiss G, Schmidt MI, Duncan BB, et al. Metabolic syndrome risk for cardiovascular disease and diabetes in the ARIC study. Int J Obes (Lond). 2008;32(Suppl 2):S21–4. https://doi.org/10.1038/ijo.2008.31.

    Article  PubMed Central  CAS  Google Scholar 

  2. Vagovicova P, Mlikova Seidlerova J, Mayer O Jr, Wohlfahrt P, Cifkova R, Filipovsky J. Differential effect of metabolic syndrome on various parameters of arterial stiffness. Blood Press. 2015;24(4):206–11. https://doi.org/10.3109/08037051.2015.1049420.

    Article  PubMed  CAS  Google Scholar 

  3. Scuteri A, Cunha PG, Rosei EA, Badariere J, Bekaert S, Cockcroft JR, et al. Arterial stiffness and influences of the metabolic syndrome: a cross-countries study. Atherosclerosis. 2014;233(2):654–60. https://doi.org/10.1016/j.atherosclerosis.2014.01.041.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Ferreira I, Boreham CA, Twisk JW, Gallagher AM, Young IS, Murray LJ, et al. Clustering of metabolic syndrome risk factors and arterial stiffness in young adults: the Northern Ireland young hearts project. J Hypertens. 2007;25(5):1009–20. https://doi.org/10.1097/HJH.0b013e3280a94e76.

    Article  PubMed  CAS  Google Scholar 

  5. Stehouwer CD, Henry RM, Ferreira I. Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease. Diabetologia. 2008;51(4):527–39. https://doi.org/10.1007/s00125-007-0918-3.

    Article  PubMed  CAS  Google Scholar 

  6. Gall J, Frisdal E, Bittar R, Le Goff W, Bruckert E, Lesnik P, et al. Association of Cholesterol Efflux Capacity With Clinical Features of Metabolic Syndrome: Relevance to Atherosclerosis. J Am Heart Assoc. 2016;5(12) https://doi.org/10.1161/jaha.116.004808.

  7. Fu Y. Rate-limiting factors of cholesterol efflux in reverse cholesterol transport: acceptors and donors. Clin Exp Pharmacol Physiol. 2010;37(7):703–9. https://doi.org/10.1111/j.1440-1681.2010.05386.x.

    Article  PubMed  CAS  Google Scholar 

  8. Cavelier C, Lorenzi I, Rohrer L, von Eckardstein A. Lipid efflux by the ATP-binding cassette transporters ABCA1 and ABCG1. Biochim Biophys Acta. 2006;1761(7):655–66. https://doi.org/10.1016/j.bbalip.2006.04.012.

    Article  PubMed  CAS  Google Scholar 

  9. Liao S, McLachlan CS. Cholesterol Efflux: Does It Contribute to Aortic Stiffening? J Cardiovasc Dev Dis. 2018;5(2) https://doi.org/10.3390/jcdd5020023.

  10. Vaisman BL, Demosky SJ, Stonik JA, Ghias M, Knapper CL, Sampson ML, et al. Endothelial expression of human ABCA1 in mice increases plasma HDL cholesterol and reduces diet-induced atherosclerosis. J Lipid Res. 2012;53(1):158–67. https://doi.org/10.1194/jlr.M018713.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Westerterp M, Tsuchiya K, Tattersall IW, Fotakis P, Bochem AE, Molusky MM, et al. Deficiency of ATP-binding cassette transporters A1 and G1 in endothelial cells accelerates atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 2016;36(7):1328–37. https://doi.org/10.1161/atvbaha.115.306670.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Castiglioni S, Monti M, Arnaboldi L, Canavesi M, Ainis Buscherini G, Calabresi L, et al. ABCA1 and HDL3 are required to modulate smooth muscle cells phenotypic switch after cholesterol loading. Atherosclerosis. 2017;266:8–15. https://doi.org/10.1016/j.atherosclerosis.2017.09.012.

    Article  PubMed  CAS  Google Scholar 

  13. Bi X, Vitali C, Cuchel M. ABCA1 and inflammation: from animal models to humans. Arterioscler Thromb Vasc Biol. 2015;35(7):1551–3. https://doi.org/10.1161/atvbaha.115.305547.

    Article  PubMed  CAS  Google Scholar 

  14. Cavalcante JL, Lima JA, Redheuil A, Al-Mallah MH. Aortic stiffness: current understanding and future directions. J Am Coll Cardiol. 2011;57(14):1511–22. https://doi.org/10.1016/j.jacc.2010.12.017.

    Article  PubMed  Google Scholar 

  15. Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol. 2010;55(13):1318–27. https://doi.org/10.1016/j.jacc.2009.10.061.

    Article  PubMed  Google Scholar 

  16. Mitchell GF, Hwang SJ, Vasan RS, Larson MG, Pencina MJ, Hamburg NM, et al. Arterial stiffness and cardiovascular events: the Framingham heart study. Circulation. 2010;121(4):505–11. https://doi.org/10.1161/circulationaha.109.886655.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Janic M, Lunder M, Sabovic M. Arterial stiffness and cardiovascular therapy. Biomed Res Int. 2014;2014:621437–11. https://doi.org/10.1155/2014/621437.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Giudici F, Qian Y, O'Rourke M, Avolio A. Simulation of reduction of proximal aortic stiffness by an elastic wrap and effects on pulse pressure. Conf Proc IEEE Eng Med Biol Soc. 2012;2012:657–60. https://doi.org/10.1109/embc.2012.6346017.

    Article  PubMed  Google Scholar 

  19. Robich MP, Osipov RM, Chu LM, Han Y, Feng J, Nezafat R, et al. Resveratrol modifies risk factors for coronary artery disease in swine with metabolic syndrome and myocardial ischemia. Eur J Pharmacol. 2011;664(1–3):45–53. https://doi.org/10.1016/j.ejphar.2011.04.059.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Saraf R, Huang T, Mahmood F, Owais K, Bardia A, Khabbaz KR, et al. Early cellular changes in the ascending aorta and myocardium in a swine model of metabolic syndrome. PLoS One. 2016;11(1):e0146481. https://doi.org/10.1371/journal.pone.0146481.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Roldan CA, Alomari IB, Awad K, Boyer NM, Qualls CR, Greene ER, et al. Aortic stiffness is associated with left ventricular diastolic dysfunction in systemic lupus erythematosus: a controlled transesophageal echocardiographic study. Clin Cardiol. 2014;37(2):83–90. https://doi.org/10.1002/clc.22218.

    Article  PubMed  Google Scholar 

  22. Iliopoulos J. The aortic wrap procedure: a surgical method of treating age related aortic dilatation and stiffening [dissertation]. Sydney: University of New South Wales; 2006.

    Google Scholar 

  23. Tropea BI, Schwarzacher SP, Chang A, Asvar C, Huie P, Sibley RK, et al. Reduction of aortic wall motion inhibits hypertension-mediated experimental atherosclerosis. Arterioscler Thromb Vasc Biol. 2000;20(9):2127–33.

    Article  PubMed  CAS  Google Scholar 

  24. Li XM, Tang WH, Mosior MK, Huang Y, Wu Y, Matter W, et al. Paradoxical association of enhanced cholesterol efflux with increased incident cardiovascular risks. Arterioscler Thromb Vasc Biol. 2013;33(7):1696–705. https://doi.org/10.1161/atvbaha.113.301373.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Favari E, Calabresi L, Adorni MP, Jessup W, Simonelli S, Franceschini G, et al. Small discoidal pre-beta1 HDL particles are efficient acceptors of cell cholesterol via ABCA1 and ABCG1. Biochemistry. 2009;48(46):11067–74. https://doi.org/10.1021/bi901564g.

    Article  PubMed  CAS  Google Scholar 

  26. Villard EF, El Khoury P, Duchene E, Bonnefont-Rousselot D, Clement K, Bruckert E, et al. Elevated CETP activity improves plasma cholesterol efflux capacity from human macrophages in women. Arterioscler Thromb Vasc Biol. 2012;32(10):2341–9. https://doi.org/10.1161/atvbaha.112.252841.

    Article  PubMed  CAS  Google Scholar 

  27. Low H, Hoang A, Sviridov D. Cholesterol efflux assay. J Vis Exp. 2012;61:e3810. https://doi.org/10.3791/3810.

    Article  CAS  Google Scholar 

  28. Boutouyrie P, Fliser D, Goldsmith D, Covic A, Wiecek A, Ortiz A, et al. Assessment of arterial stiffness for clinical and epidemiological studies: methodological considerations for validation and entry into the European renal and cardiovascular medicine registry. Nephrol Dial Transplant. 2014;29(2):232–9. https://doi.org/10.1093/ndt/gft309.

    Article  PubMed  Google Scholar 

  29. Park S, Lakatta EG. Role of inflammation in the pathogenesis of arterial stiffness. Yonsei Med J. 2012;53(2):258–61. https://doi.org/10.3349/ymj.2012.53.2.258.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Emre A, Oz D, Yesilcimen K, Sayar N, Ergun D. Impact of the metabolic syndrome on aortic pulse pressure and ascending aortic pulsatility in patients with angiographically normal coronary arteries. Can J Cardiol. 2009;25(7):411–4.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Annema W, Dikkers A, de Boer JF, van Greevenbroek MM, van der Kallen CJ, Schalkwijk CG, et al. Impaired HDL cholesterol efflux in metabolic syndrome is unrelated to glucose tolerance status: the CODAM study. Sci Rep. 2016;6:27367. https://doi.org/10.1038/srep27367.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Borja MS, Hammerson B, Tang C, Savinova OV, Shearer GC, Oda MN. Apolipoprotein A-I exchange is impaired in metabolic syndrome patients asymptomatic for diabetes and cardiovascular disease. 2017;12(8):e0182217. https://doi.org/10.1371/journal.pone.0182217.

  33. Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med. 2011;364(2):127–35. https://doi.org/10.1056/NEJMoa1001689.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Dubland JA, Francis GA. So much cholesterol: the unrecognized importance of smooth muscle cells in atherosclerotic foam cell formation. Curr Opin Lipidol. 2016;27(2):155–61. https://doi.org/10.1097/mol.0000000000000279.

    Article  PubMed  CAS  Google Scholar 

  35. Prosser HC, Ng MK, Bursill CA. The role of cholesterol efflux in mechanisms of endothelial protection by HDL. Curr Opin Lipidol. 2012;23(3):182–9. https://doi.org/10.1097/MOL.0b013e328352c4dd.

    Article  PubMed  CAS  Google Scholar 

  36. Munch G, Bultmann A, Li Z, Holthoff HP, Ullrich J, Wagner S, et al. Overexpression of ABCG1 protein attenuates arteriosclerosis and endothelial dysfunction in atherosclerotic rabbits. Heart Int. 2012;7(2):e12. https://doi.org/10.4081/hi.2012.e12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Liu D, Ji L, Tong X, Pan B, Han JY, Huang Y, et al. Human apolipoprotein A-I induces cyclooxygenase-2 expression and prostaglandin I-2 release in endothelial cells through ATP-binding cassette transporter A1. Am J Phys Cell Physiol. 2011;301(3):C739–48. https://doi.org/10.1152/ajpcell.00055.2011.

    Article  CAS  Google Scholar 

  38. Bochem AE, van Wijk DF, Holleboom AG, Duivenvoorden R, Motazacker MM, Dallinga-Thie GM, et al. ABCA1 mutation carriers with low high-density lipoprotein cholesterol are characterized by a larger atherosclerotic burden. Eur Heart J. 2013;34(4):286–91. https://doi.org/10.1093/eurheartj/ehs376.

    Article  PubMed  CAS  Google Scholar 

  39. van Dam MJ, de Groot E, Clee SM, Hovingh GK, Roelants R, Brooks-Wilson A, et al. Association between increased arterial-wall thickness and impairment in ABCA1-driven cholesterol efflux: an observational study. Lancet. 2002;359(9300):37–42. https://doi.org/10.1016/s0140-6736(02)07277-x.

    Article  PubMed  Google Scholar 

  40. Favari E, Ronda N, Adorni MP, Zimetti F, Salvi P, Manfredini M, et al. ABCA1-dependent serum cholesterol efflux capacity inversely correlates with pulse wave velocity in healthy subjects. J Lipid Res. 2013;54(1):238–43. https://doi.org/10.1194/jlr.P030452.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Mourmoura E, Vasilaki A, Giannoukas A, Michalodimitrakis E, Pavlidis P, Tsezou A. Evidence of deregulated cholesterol efflux in abdominal aortic aneurysm. Acta Histochem. 2016;118(2):97–108. https://doi.org/10.1016/j.acthis.2015.11.012.

    Article  PubMed  CAS  Google Scholar 

  42. Aiello RJ, Brees D, Francone OL. ABCA1-deficient mice: insights into the role of monocyte lipid efflux in HDL formation and inflammation. Arterioscler Thromb Vasc Biol. 2003;23(6):972–80. https://doi.org/10.1161/01.atv.0000054661.21499.fb.

    Article  PubMed  CAS  Google Scholar 

  43. Tang C, Liu Y, Kessler PS, Vaughan AM, Oram JF. The macrophage cholesterol exporter ABCA1 functions as an anti-inflammatory receptor. J Biol Chem. 2009;284(47):32336–43. https://doi.org/10.1074/jbc.M109.047472.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Babashamsi MM, Halalkhor S, Moradi Firouzjah H, Parsian H, Jalali SF, Babashamsi M. Association of ATP-binding cassette transporter A1 (ABCA1)-565 C/T gene polymorphism with Hypoalphalipoproteinemia and serum lipids, IL-6 and CRP levels. Avicenna J Med Biotechnol. 2017;9(1):38–43.

    PubMed  PubMed Central  Google Scholar 

  45. Li C, Guo R, Lou J, Zhou H. The transcription levels of ABCA1, ABCG1 and SR-BI are negatively associated with plasma CRP in Chinese populations with various risk factors for atherosclerosis. Inflammation. 2012;35(5):1641–8. https://doi.org/10.1007/s10753-012-9479-9.

    Article  PubMed  CAS  Google Scholar 

  46. Xu M, Zhou H, Gu Q, Li C. The expression of ATP-binding cassette transporters in hypertensive patients. Hypertens Res. 2009;32(6):455–61. https://doi.org/10.1038/hr.2009.46.

    Article  PubMed  CAS  Google Scholar 

  47. Chawla A, Boisvert WA, Lee CH, Laffitte BA, Barak Y, Joseph SB, et al. A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell. 2001;7(1):161–71.

    Article  PubMed  CAS  Google Scholar 

  48. Ameshima S, Golpon H, Cool CD, Chan D, Vandivier RW, Gardai SJ, et al. Peroxisome proliferator-activated receptor gamma (PPARgamma) expression is decreased in pulmonary hypertension and affects endothelial cell growth. Circ Res. 2003;92(10):1162–9. https://doi.org/10.1161/01.res.0000073585.50092.14.

    Article  PubMed  CAS  Google Scholar 

  49. Bigazzi F, Adorni MP, Puntoni M, Sbrana F, Lionetti V, Pino BD, et al. Analysis of serum cholesterol efflux capacity in a Minipig model of nonischemic heart failure. J Atheroscler Thromb. 2017;24(8):853–62. https://doi.org/10.5551/jat.37101.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Zhu M, Fu Y, Hou Y, Wang N, Guan Y, Tang C, et al. Laminar shear stress regulates liver X receptor in vascular endothelial cells. Arterioscler Thromb Vasc Biol. 2008;28(3):527–33. https://doi.org/10.1161/atvbaha.107.143487.

    Article  PubMed  CAS  Google Scholar 

  51. Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet. 2001;358(9298):2026–33. https://doi.org/10.1016/s0140-6736(01)07098-2.

    Article  PubMed  CAS  Google Scholar 

  52. Tian L, Wu X, Fu M, Qin Y, Xu Y, Jia L. Relationship between plasma apolipoproteinB concentrations, apolipoproteinB/apolipoproeinA-I and HDL subclasses distribution. Clin Chim Acta. 2008;388(1–2):148–55. https://doi.org/10.1016/j.cca.2007.10.028.

    Article  PubMed  CAS  Google Scholar 

  53. Corsetti JP, Zareba W, Moss AJ, Sparks CE. Apolipoprotein B determines risk for recurrent coronary events in postinfarction patients with metabolic syndrome. Atherosclerosis. 2004;177(2):367–73. https://doi.org/10.1016/j.atherosclerosis.2004.07.019.

    Article  PubMed  CAS  Google Scholar 

  54. Heinecke JW. The not-so-simple HDL story: a new era for quantifying HDL and cardiovascular risk? Nat Med. 2012;18(9):1346–7. https://doi.org/10.1038/nm.2930.

    Article  PubMed  CAS  Google Scholar 

  55. Marcovina S, Packard CJ. Measurement and meaning of apolipoprotein AI and apolipoprotein B plasma levels. J Intern Med. 2006;259(5):437–46. https://doi.org/10.1111/j.1365-2796.2006.01648.x.

    Article  PubMed  CAS  Google Scholar 

  56. Kim MK, Ahn CW, Kang S, Ha JY, Baek H, Park JS, et al. Association between Apolipoprotein B/Apolipoprotein A-1 and arterial stiffness in metabolic syndrome. Clin Chim Acta. 2014;437:115–9. https://doi.org/10.1016/j.cca.2014.07.005.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the financial support from The Limingzhang Sciences Foundation (2016-451903). Shutan Liao is funded under an NHMRC Development Grant.

Author information

Authors and Affiliations

  1. Rural Clinical School, University of New South Wales, Sydney, NSW, Australia

    Shutan Liao

  2. The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Shutan Liao

  3. Department of Cardiac Surgery, The First Affiliated Hospital of Nanchang University, 53 Taohua Road, Nanchang, 330008, Jiangxi, China

    Qing Zhou & Yang Zhang

Authors
  1. Shutan Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qing Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yang Zhang.

Ethics declarations

The study protocol was approved by the Animal Ethics Committee of Nanchang University.

Conflict of interest

The authors declare that they have no conflict of interest.

Disclosures

All authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liao, S., Zhou, Q. & Zhang, Y. Elastic aortic wrap reduced aortic stiffness by partially alleviating the impairment of cholesterol efflux capacity in pigs. J Diabetes Metab Disord 17, 101–109 (2018). https://doi.org/10.1007/s40200-018-0345-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40200-018-0345-7

Keywords

Search

Navigation