Skip to main content

Advertisement

SpringerLink
Log in

Circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 levels are associated with proximal/middle segment of the LAD lesions in patients with stable coronary artery disease

  • Original Paper
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Background/Objectives

Atherosclerosis is the main underlying pathology of coronary artery disease (CAD), which is the leading cause of mortality worldwide. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in multiple phases of vascular dysfunction, including endothelial dysfunction, atherosclerotic plaque formation, and destabilization. The purpose of the current study was to determine whether soluble LOX-1 is associated with proximal/mid and distal segment of the left anterior descending (LAD) artery lesion in patients with stable CAD.

Methods

Sixty-four patients with proximal/mid segment of the LAD lesions and 51 patients with distal segments of the LAD lesions were included in this study. Soluble LOX-1 levels were measured in all study subjects.

Results

Baseline characteristics of the two groups were similar. In stable CAD, patients with proximal/middle segment of the LAD lesions had significantly higher circulating soluble LOX-1 levels than patients with distal segments of the LAD lesions (1.07 ± 0.33 vs. 0.70 ± 0.17 ng/ml, p < 0.001). No correlation was found between plasma-soluble LOX-1 levels and fasting glucose, lipid profile. For predicting proximal/middle LAD lesions, the highest specificity (95,2%) and sensitivity (53,8%) levels were obtained at the cut-off value of 0.68.

Conclusion

Our study demonstrated that serum-soluble LOX-1 levels were associated with proximal/mid segment of the LAD lesions. Furthermore, this study suggested soluble LOX-1 might be a useful biomarker of coronary plaque vulnerability in patients with stable CAD. Soluble LOX-1, the novel biochemical marker, may provide new insights into not only risk stratification but also therapeutic strategy for CAD.

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

References

  1. Mensah GA, Brown DW (2007) An overview of cardiovascular disease burden in the United States. Health Aff (Millwood) 26:38–48

    Article  Google Scholar 

  2. Grobbee DE, O’Leary DH, Bots ML, Measuring Effects on intima media Thickness: an Evaluation of Rosuvastatin study group et al (2004) Measuring Effects on intima media Thickness: an Evaluation of Rosuvastatin in sub clinical atherosclerosis—the rationale and methodology of the METEOR study. Cardiovasc Drugs Ther 18:231–238

    Article  PubMed  Google Scholar 

  3. Viles-Gonzalez JF, Fuster V, Badimon JJ (2004) Atherothrombosis: a widespread disease with unpredictable and life-threatening consequences. Eur Heart J 25:1197–1207

    Article  PubMed  CAS  Google Scholar 

  4. Jensen LO, Thayssen P, Pedersen KE, Stender S, Haghfelt T (2004) Regression of coronary atherosclerosis by simvastatin: a serial intravascular ultrasound study. Circulation 110:265–270

    Article  PubMed  CAS  Google Scholar 

  5. Rauch U, Osende JI, Fuster V, Badimon JJ, Fayad Z, Chesebro JH (2001) Thrombus formation on atherosclerotic plaques: pathogenesis and clinical consequences. Ann Intern Med 134:224–238

    PubMed  CAS  Google Scholar 

  6. Ohashi R, Mu H, Yao Q, Chen C (2004) Atherosclerosis: immunopathogenesis and immunotherapy. Med Sci Monit 10:RA255–RA260

    PubMed  Google Scholar 

  7. Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352:1685–1695

    Article  PubMed  CAS  Google Scholar 

  8. Ben-Haim S, Israel O (2006) PET/CT for atherosclerotic plaque imaging. Q J Nucl Med Mol Imaging 50:53–60

    PubMed  CAS  Google Scholar 

  9. Van Mieghem CA, McFadden EP, de Feyter PJ et al (2006) Noninvasive detection of subclinical coronary atherosclerosis coupled with assessment of changes in plaque characteristics using novel invasive imaging modalities: the Integrated Biomarker and Imaging Study (IBIS). J Am Coll Cardiol 47:1134–1142

    Article  PubMed  Google Scholar 

  10. Weissberg PL (2000) Atherogenesis: current understanding of the causes of atheroma. Heart 83:247–252

    Article  PubMed  CAS  Google Scholar 

  11. Valencia J, Bordes P, Berenguer A, Mainar V, Ruiz Nodar JM, Arrarte V (2002) Long-term follow-up of patients with proximal left anterior descending coronary artery stenosis treated with stent. Rev Esp Cardiol 55:607–615

    PubMed  Google Scholar 

  12. Brambilla N, Repetto A, Bramucci E et al (2005) Directional coronary atherectomy plus stent implantation vs. left internal mammary artery bypass grafting for isolated proximal stenosis of the left anterior descending coronary artery. Catheter Cardiovasc Interv 64:45–52

    Article  PubMed  Google Scholar 

  13. Sawamura T, Kume N, Aoyama T et al (1997) An endothelial receptor for oxidized low-density lipoprotein. Nature 386:73–77

    Article  PubMed  CAS  Google Scholar 

  14. Yoshida H, Kondratenko N, Green S, Steinberg D, Quehenberger O (1998) Identification of the lectin-like receptor for oxidized low-density lipoprotein in human macrophages and its potential role as a scavenger receptor. Biochem J 334:9–13

    PubMed  CAS  Google Scholar 

  15. Vohra RS, Murphy JE, Walker JH, Ponnambalam S, Homer-Vanniasinkam S (2006) Atherosclerosis and the Lectin-like OXidized low-density lipoprotein scavenger receptor. Trends Cardiovasc Med 16:60–64

    Article  PubMed  CAS  Google Scholar 

  16. Mehta JL, Chen J, Hermonat PL, Romeo F, Novelli G (2006) Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1): a critical player in the development of atherosclerosis and related disorders. Cardiovasc Res 69:36–45

    Article  PubMed  CAS  Google Scholar 

  17. Kume N, Murase T, Moriwaki H et al (1998) Inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells. Circ Res 83:322–327

    PubMed  CAS  Google Scholar 

  18. Conti CR, Mehta JL (1987) Acute myocardial ischemia: role of atherosclerosis, thrombosis, platelet activation, coronary vasospasm, and altered arachidonic acid metabolism. Circulation 75:V84–V95

    PubMed  CAS  Google Scholar 

  19. Lee RT, Libby P (1997) The unstable atheroma. Arterioscler Thromb Vasc Biol 17:1859–1867

    Article  PubMed  CAS  Google Scholar 

  20. Rouis M, Adamy C, Duverger N et al (1999) Adenovirus-mediated overexpression of tissue inhibitor of metalloproteinase-1 reduces atherosclerotic lesions in apolipoprotein E-deficient mice. Circulation 100:533–540

    PubMed  CAS  Google Scholar 

  21. Pasterkamp G, Schoneveld AH, Hijnen DJ et al (2000) Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteases 1, 2 and 9 in the human coronary artery. Atherosclerosis 150:245–253

    Article  PubMed  CAS  Google Scholar 

  22. Li D, Mehta JL (2000) Upregulation of endothelial receptor for oxidized LDL (LOX–1) by oxidized LDL and implications in apoptosis of human coronary artery endothelial cells: evidence from use of antisense LOX–1 mRNA and chemical inhibitors. Arterioscler Thromb Vasc Biol 20:1116–1122

    Article  PubMed  CAS  Google Scholar 

  23. Murase T, Kume N, Kataoka H et al (2000) Identification of soluble forms of lectin-like oxidized LDL receptor-1. Arterioscler Thromb Vasc Biol 20:715–720

    Article  PubMed  CAS  Google Scholar 

  24. El Fawal MA, Berg GA, Wheatley DJ, Harland WA (1987) Sudden coronary death in Glasgow: nature and frequency of acute coronary lesions. Br Heart J 57:329–335

    Article  PubMed  CAS  Google Scholar 

  25. Fox B, James K, Morgan B, Seed A (1982) Distribution of fatty and fibrous plaques in young human coronary arteries. Atherosclerosis 41:337–347

    Article  PubMed  CAS  Google Scholar 

  26. Gibson CM, Kirtane AJ, Murphy SA et al (2003) Distance from the coronary ostium to the culprit lesion in acute ST-elevation myocardial infarction and its implications regarding the potential prevention of proximal plaque rupture. J Thromb Thrombolysis 15:189–196

    Article  PubMed  Google Scholar 

  27. Hochman JS, Phillips WJ, Ruggieri D, Ryan SF (1988) The distribution of atherosclerotic lesions in the coronary arterial tree: relation to cardiac risk factors. Am Heart J 116:1217–1222

    Article  PubMed  CAS  Google Scholar 

  28. Vieweg WV, Alpert JS, Johnson AD et al (1979) Distribution and severity of coronary artery disease in 500 patients with angina pectoris. Cathet Cardiovasc Diagn 5:319–330

    Article  PubMed  CAS  Google Scholar 

  29. Wang JC, Normand SL, Mauri L, Kuntz RE (2004) Coronary artery spatial distribution of acute myocardial infarction occlusions. Circulation 110:278–842

    Article  PubMed  Google Scholar 

  30. Virmani R, Burke AP, Farb A, Kolodgie FD (2006) Pathology of the vulnerable plaque. J Am Coll Cardiol 47(8 Suppl):C13–C18

    Article  PubMed  CAS  Google Scholar 

  31. Davies MJ (2000) The pathophysiology of acute coronary syndromes. Heart 83:361–366

    Article  PubMed  CAS  Google Scholar 

  32. Katritsis DG, Efstathopoulos EP, Pantos J, Korovesis et al (2008) Anatomic characteristics of culprit sites in acute coronary syndromes. J Interv Cardiol 21:140–150

    Article  PubMed  Google Scholar 

  33. Valencia J, Berenguer A, Mainar V et al (2006) Two-year follow-up of sirolimus-eluting stents for the treatment of proximal left anterior descending coronary artery stenosis. J Interv Cardiol 19:126–134

    Article  PubMed  Google Scholar 

  34. Falk E, Shah PK, Fuster V (1995) Coronary plaque disruption. Circulation 92:657–671

    PubMed  CAS  Google Scholar 

  35. Katritsis DG, Pantos J, Efstathopoulos E (2007) Hemodynamic factors and atheromatic plaque rupture in the coronary arteries: from vulnerable plaque to vulnerable coronary segment. Coron Artery Dis 18:229–237

    Article  PubMed  Google Scholar 

  36. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 285:2486–2497

    Article  Google Scholar 

  37. Smith SC Jr, Allen J, Blair SN et al (2006) AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update endorsed by the National Heart, Lung, and Blood Institute. J Am Coll Cardiol 47:2130–2139

    Article  PubMed  Google Scholar 

  38. Witztum JL, Steinberg D (1991) Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 88:1785–1792

    Article  PubMed  CAS  Google Scholar 

  39. Chen J, Mehta JL (2004) Role of oxidative stress in coronary heart disease. Indian Heart J 56:163–173

    PubMed  Google Scholar 

  40. Erl W, Weber PC, Weber C (1998) Monocytic cell adhesion to endothelial cells stimulated by oxidized low density lipoprotein is mediated by distinct endothelial ligands. Atherosclerosis 136:297–303

    Article  PubMed  CAS  Google Scholar 

  41. Keaney JF Jr, Guo Y, Cunningham D, Shwaery GT, Xu A, Vita JA (1996) Vascular incorporation of alpha-tocopherol prevents endothelial dysfunction due to oxidized LDL by inhibiting protein kinase C stimulation. J Clin Invest 98:386–394

    Article  PubMed  CAS  Google Scholar 

  42. Mehta A, Yang B, Khan S, Hendricks JB, Stephen C, Mehta JL (1995) Oxidized low-density lipoproteins facilitate leukocyte adhesion to aortic intima without affecting endothelium-dependent relaxation. Role of P-selectin. Arterioscler Thromb Vasc Biol 15:2076–2083

    Article  PubMed  CAS  Google Scholar 

  43. Ehara S, Ueda M, Naruko T et al (2001) Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation 103:1955–1960

    PubMed  CAS  Google Scholar 

  44. Tsimikas S, Witztum JL (2001) Measuring circulating oxidized low-density lipoprotein to evaluate coronary risk. Circulation 103:1930–1932

    PubMed  CAS  Google Scholar 

  45. Kume N, Kita T (2002) New scavenger receptors and their functions in atherogenesis. Curr Atheroscler Rep 4:253–257

    Article  PubMed  Google Scholar 

  46. Kataoka H, Kume N, Miyamoto S, Minami M, Morimoto M, Hayashida K et al (2001) Oxidized LDL modulates Bax/Bcl-2 through the lectinlike Ox-LDL receptor-1 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 21:955–960

    Article  PubMed  CAS  Google Scholar 

  47. Kume N, Kita T (2004) Apoptosis of vascular cells by oxidized LDL: involvement of caspases and LOX-1 and its implication in atherosclerotic plaque rupture. Circ Res 94:269–270

    Article  PubMed  CAS  Google Scholar 

  48. Li D, Liu L, Chen H, Sawamura T, Ranganathan S, Mehta JL (2003) LOX-1 mediates oxidized low-density lipoprotein-induced expression of matrix metalloproteinases in human coronary artery endothelial cells. Circulation 107:612–617

    Article  PubMed  CAS  Google Scholar 

  49. Li DY, Zhang YC, Philips MI, Sawamura T, Mehta JL (1999) Upregulation of endothelial receptor for oxidized low-density lipoprotein (LOX-1) in cultured human coronary artery endothelial cells by angiotensin II type 1 receptor activation. Circ Res 84:1043–1049

    PubMed  CAS  Google Scholar 

  50. Kume N, Murase T, Moriwaki H et al (1998) Inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells. Circ Res 83:322–327

    PubMed  CAS  Google Scholar 

  51. Murase T, Kume N, Korenaga R et al (1998) Fluid shear stress transcriptionally induces lectin-like oxidized LDL receptor-1 in vascular endothelial cells. Circ Res 83(3):328–333

    PubMed  CAS  Google Scholar 

  52. Silence J, Lupu F, Collen D, Lijnen HR (2001) Persistence of atherosclerotic plaque but reduced aneurysm formation in mice with stromelysin-1 (MMP-3) gene inactivation. Arterioscler Thromb Vasc Biol 21:1440–1445

    Article  PubMed  CAS  Google Scholar 

  53. Lemaître V, O’Byrne TK, Borczuk AC, Okada Y, Tall AR, D’Armiento J (2001) ApoE knockout mice expressing human matrix metalloproteinase-1 in macrophages have less advanced atherosclerosis. J Clin Invest 107:1227–1234

    Article  PubMed  Google Scholar 

  54. Chen H, Li D, Sawamura T, Inoue K, Mehta JL (2000) Upregulation of LOX–1 expression in aorta of hypercholesterolemic rabbits: modulation by losartan. Biochem Biophys Res Commun 276:1100–1104

    Article  PubMed  CAS  Google Scholar 

  55. Hayashida K, Kume N, Murase T et al (2005) Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 levels are elevated in acute coronary syndrome: a novel marker for early diagnosis. Circulation 112:812–818

    Article  PubMed  CAS  Google Scholar 

  56. Kume N, Mitsuoka H, Hayashida K, Tanaka M, Kita T (2010) Soluble lectin-like oxidized low-density lipoprotein receptor-1 predicts prognosis after acute coronary syndrome-a pilot study. Circ J 74:1399–1404

    Article  PubMed  CAS  Google Scholar 

  57. Ishino S, Mukai T, Kume N et al (2007) Lectin-like oxidized LDL receptor-1 (LOX-1) expression is associated with atherosclerotic plaque instability—analysis in hypercholesterolemic rabbits. Atherosclerosis 195:48–56

    Article  PubMed  CAS  Google Scholar 

  58. Kuge Y, Kume N, Ishino S et al (2008) Prominent lectin-like oxidized low density lipoprotein (LDL) receptor-1 (LOX-1) expression in atherosclerotic lesions is associated with tissue factor expression and apoptosis in hypercholesterolemic rabbits. Biol Pharm Bull 31:1475–1482

    Article  PubMed  CAS  Google Scholar 

  59. Ishino S, Mukai T, Kuge Y et al (2008) Targeting of lectinlike oxidized low-density lipoprotein receptor 1 (LOX-1) with 99mTc-labeled anti-LOX-1 antibody: potential agent for imaging of vulnerable plaque. J Nucl Med 49:1677–1685

    Article  PubMed  CAS  Google Scholar 

  60. Mehta JL, Sanada N, Hu CP et al (2007) Deletion of LOX-1 reduces atherogenesis in LDLR knockout mice fed high cholesterol diet. Circ Res 100:1634–1642

    Article  PubMed  CAS  Google Scholar 

  61. Sipahi I, Tuzcu EM, Schoenhagen P et al (2006) Paradoxical increase in lumen size during progression of coronary atherosclerosis: observations from the REVERSAL trial. Atherosclerosis 189:229–235

    Article  PubMed  CAS  Google Scholar 

  62. Stary HC (1989) Evolution and progression of atherosclerotic lesions in coronary arteries of children and young adults. Arteriosclerosis 9(1 Suppl):I19–I32

    PubMed  CAS  Google Scholar 

  63. Valgimigli M, Rodriguez-Granillo GA, Garcia-Garcia HM et al (2006) Distance from the ostium as an independent determinant of coronary plaque composition in vivo: an intravascular ultrasound study based radiofrequency data analysis in humans. Eur Heart J 27:655–663

    Article  PubMed  Google Scholar 

  64. Valgimigli M, Rodriguez-Granillo GA, Garcia-Garcia HM et al (2007) Plaque composition in the left main stem mimics the distal but not the proximal tract of the left coronary artery: influence of clinical presentation, length of the left main trunk, lipid profile, and systemic levels of C-reactive protein. J Am Coll Cardiol 49:23–31

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

No funding supported this study.

Author information

Authors and Affiliations

  1. Department of Cardiology, Elazig Education and Research Hospital, Elazig, Turkey

    Mehmet Balın, Ahmet Celik & M. Ali Kobat

Authors
  1. Mehmet Balın
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ahmet Celik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Ali Kobat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mehmet Balın.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Balın, M., Celik, A. & Kobat, M.A. Circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 levels are associated with proximal/middle segment of the LAD lesions in patients with stable coronary artery disease. Clin Res Cardiol 101, 247–253 (2012). https://doi.org/10.1007/s00392-011-0386-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-011-0386-0

Keywords

Search

Navigation