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Relationship between lectin-like oxidized low-density lipoprotein receptor 1 expression and preoperative echogenic findings of vulnerable carotid plaque

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Abstract

Purpose

Lectin-like oxidized low-density lipoprotein 1 (LOX1) is an important cell surface receptor for the progression of atherosclerosis. Our purpose is to clarify the relationships of LOX1 and atherosclerotic factors for the vulnerability of carotid plaque and preoperative echogenic findings.

Methods

We examined LOX1 expression, matrix metalloproteinase (MMP)-2,9, and tissue inhibitor of MMP (TIMP)-2 by immunohistochemical analysis using carotid endarterectomy specimens obtained from 14 patients. Groups were divided into stable plaque group A and vulnerable plaque group B by preoperative echogenic findings of carotid plaques. Endothelial immunoreactivity was calculated, and the immunohistochemical findings were compared.

Results

LOX1 was remarkably expressed, especially in smooth muscle cells in vulnerable plaque and colocalized in MMP-9 positive cells and apoptotic cells. All LOX1, MMP-2,9, and TIMP2 were remarkably expressed in the subendothelial layer in group B compared with group A. The endothelial LOX1 index was 63.75 ± 4.92 in group A and 83.0 ± 5.02 in group B (p = 0.02). The endothelial MMP-2 index was 24.38 ± 5.50 in group A and 32.83 ± 6.79 in group B (p = 0.01). The endothelial MMP-9 index was 46.13 ± 6.31 in group A and 59.17 ± 2.14 in group B (p = 0.002). The endothelial TIMP-2 index had no significant difference between two groups (p = 0.14).

Conclusion

LOX-1 may play an important role in the progression of vulnerable carotid plaque and might regulate vulnerable plaque formation in cooperation with MMPs and TIMP-2. Endothelial MMP-2 might suppress TIMP-2 activation in vulnerable plaques.

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References

  1. Alverez B, Ruiz C, Chacon P, Alverez-Sabin J, Matas M (2004) Serum values of metalloproteinase-2 and metalloproteinase-9 as related to unstable plaque and inflammatory cells in patients with greater than 70% carotid artery stenosis. J Vasc Surg 40:469–475

    Article  Google Scholar 

  2. Chen XP, Zhang TT, Du GH (2007) Lectin-like oxidized low-density lipoprotein receptor-1, a new promising target for the therapy of atherosclerosis? Cardiovasc Drug Rev 25:146–161

    Article  CAS  PubMed  Google Scholar 

  3. Cominacini L, Pasini AF, Garbin U (2000) Oxidized low density lipoprotein (ox-LDL) binding to ox-LDL receptor-1 in endothelial cells induces the activation of NF-kappaB through an increased production of intracellular reactive oxygen species. J Biol Chem 27:12633–12638

    Article  Google Scholar 

  4. Gails ZS, Sukhova GK, Lark MW, Libby P (1994) Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 94:2493–2503

    Article  Google Scholar 

  5. Gimbrone MA Jr, Cybulsky MI, Kume N, Collins T, Resnick N (1995) Vascular endothelium: an integrator of pathophysiological stimuli in atherogenesis. Ann NY Acad Sci 748:122–132

    Article  CAS  PubMed  Google Scholar 

  6. Gronholdt ML, Nordestgaard BG, Schroeder TV (2001) Ultrasound echolucent carotid plaques predict future strokes. Circulation 104:68–73

    Article  CAS  PubMed  Google Scholar 

  7. Honda M, Kitagawa N, Tsutsumi K (2006) High-resolution magnetic resonance imaging for detection of carotid plaques. Neurosurgery 58:338–346

    Article  PubMed  Google Scholar 

  8. Ingueneau C, Huynh-DoU TJC, Negre-Salvayre A, Salvayre R, Vindis C (2008) Caveolin-1 sensitizes vascular smooth muscle cells to mildly oxidized LDL-induced apoptosis. Biochem Biophys Res Comm 369:889–893

    Article  CAS  PubMed  Google Scholar 

  9. Ishino S, Mukai T, Kuge Y, Kume N, Ogawa M, Takai N, Kamihashi J, Shiomi M, Minami M, Kita T, Saji H (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 Nuc Med 49:1677–1685

    Article  CAS  Google Scholar 

  10. Kataoka H, Kume N, Miyamoto S, Minami M, Moriwaki H, Murase T, Sawamura M, Masaki T, Hashimoto N, Kita T (1999) Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions. Circulation 99:3111–3117

    Google Scholar 

  11. Li DY, Chen HJ, Staples ED, Ozaki K, Annex B, Singh BK, Vermani R, Mehta JL (2002) Oxidized low-density lipoprotein receptor LOX-1 and apoptosis in human atherosclerotic lesions. J Cardiovasc Pharmacol Ther 7:147–153

    Article  CAS  PubMed  Google Scholar 

  12. Li L, Renier G (2009) The oral anti-diabetic agent, gliclazide, inhibits oxidized LDL-mediated LOX-1 expression, metalloproteinase-9 secretion and apoptosis in human aortic endothelial cells. Atherosclerosis 204:40–46

    Article  CAS  PubMed  Google Scholar 

  13. O’Brien KD, Allen MD, McDonald TO, Chait A, Harlan JM, Fishbein D (1993) Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques: implications for the mode of progression of advanced coronary atherosclerosis. J Clin Invest 92:945–951

    Article  PubMed  Google Scholar 

  14. Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990's. Nature 362:801–809

    Article  CAS  PubMed  Google Scholar 

  15. Ruberg FL, Leopold JA (2002) Atherothrombosis: plaque instability and thrombogenesis. Prog Cardiovasc Dis 44:381–394

    Article  CAS  PubMed  Google Scholar 

  16. Sawamura T, Kume N, Aoyama T, Moriwaki H, Aiba Y, Tanaka T, Miwa S, Katsura Y, Kita T, Masaki T (1997) A novel receptor for oxidized low-density lipoprotein. Nature 386:73–77

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Tohoku University Hospital Emergency Center, Konan Hospital, Sendai, Japan

    Atsushi Saito, Hiroaki Shimizu & Teiji Tominaga

  2. Department of Neurosurgery, Konan Hospital, Sendai, Japan

    Miki Fujimura & Takashi Inoue

  3. Department of Neuroendovascular Therapy, Graduate School of Medicine, Tohoku University, Sendai, Japan

    Atsushi Saito, Miki Fujimura, Takashi Inoue, Hiroaki Shimizu & Teiji Tominaga

  4. Department of Neurosurgery, Graduate School of Medicine, Tohoku University, 1-1 Seiryomachi, Aoba, Sendai, Miyagi, 980-8574, Japan

    Atsushi Saito

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  1. Atsushi Saito
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  2. Miki Fujimura
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  3. Takashi Inoue
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  4. Hiroaki Shimizu
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Correspondence to Atsushi Saito.

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Saito, A., Fujimura, M., Inoue, T. et al. Relationship between lectin-like oxidized low-density lipoprotein receptor 1 expression and preoperative echogenic findings of vulnerable carotid plaque. Acta Neurochir 152, 589–595 (2010). https://doi.org/10.1007/s00701-009-0573-1

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  • DOI: https://doi.org/10.1007/s00701-009-0573-1

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