Skip to main content

Advertisement

Log in

Elevated level of ADAMTS4 in plasma and peripheral monocytes from patients with acute coronary syndrome

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

Abstract

Objectives

A recent study shows that ADAMTS4 is expressed in macrophage-rich areas of human atherosclerotic carotid plaques and coronary unstable plaques, suggesting a pathogenic role of ADAMTS4 in the development of acute coronary syndrome (ACS). We investigated (a) whether the expression level of ADAMTS4 in plasma and peripheral blood mononuclear cells was affected; and (b) whether there was a relationship with hs-CRP level and the stability of coronary atherosclerotic plaque in patients with ACS.

Methods

Our study included 30 normal controls and 120 patients including 40 with stable angina (SA), 50 with unstable angina (UA), and 30 with acute myocardial infarction (AMI). The expression of ADAMTS4 in monocytes was analyzed by RT-PCR and plasma ADAMTS4 level was determined by ELISA. All coronary stenosis with >30% diameter reduction was assessed by angiographic coronary stenosis morphology.

Results

Patients with ACS showed a significant increase of ADAMTS4 (2.7 ± 0.4) expression in monocytes compared with controls (1.1 ± 0.2) and the SA group (1.3 ± 0.2) (P < 0.001). Plasma ADAMTS4 also showed a higher level in ACS patients (100.2 ± 31.6 ng/ml) than in control (47.5 ± 9.0 ng/ml, P < 0.001) and the SA group (54.3 ± 13.2 ng/ml, P < 0.001). Moreover, we found a positive correlation between hs-CRP and ADAMTS4 expression in monocytes as well as in plasma. There was also a positive correlation of ADAMTS4 expression in monocytes and plasma with complex coronary stenosis (r 1 = 0.61, r 2 = 0.57, P < 0.001).

Conclusions

Patients with ACS showed increased ADAMTS4 expression, which may aggravate the development of atherosclerosis and instability of atherosclerotic plaques. Therefore, the ADAMTS4 expression may be a valuable marker for predicting the severity of ACS.

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

Access this article

Subscribe and save

Springer+
from $39.99 /Month
  • Starting from 10 chapters or articles per month
  • Access and download chapters and articles from more than 300k books and 2,500 journals
  • Cancel anytime
View plans

Buy Now

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Tang BL (2001) ADAMTS: a novel family of extracellular matrix proteases. Int J Biochem Cell Biol 3:33–44

    Article  Google Scholar 

  2. Newby AC (2005) Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol Rev 85:1–31

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Kuno K, Matsushima K (1998) ADAMTS-1 protein anchors at the extracellular matrix through the thrombospondin type I motifs and its spacing region. J Biol Chem 273:13912–13917

    Article  CAS  PubMed  Google Scholar 

  5. Merrilees MJ, Beaumont B, Scott LJ (2001) Comparison of deposits of versican, biglycan and decorin in saphenous vein and internal thoracic, radial and coronary arteries: correlation to patency. Coron Artery Dis 12:7–16

    Article  CAS  PubMed  Google Scholar 

  6. Yao LY, Moody C, Schonherr E, Wight TN, Sandell LJ (1994) Identification of the proteoglycan versican in aorta and smooth muscle cells by DNA sequence analysis, in situ hybridization and immunohistochemistry. Matrix Biol 14:213–225

    Article  CAS  PubMed  Google Scholar 

  7. Theocharis AD, Tsolakis I, Hjerpe A, Karamanos NK (2001) Human abdominal aortic aneurysm is characterized by decreased versican concentration and specific downregulation of versican isoform V(0). Atherosclerosis 154:367–376

    Article  CAS  PubMed  Google Scholar 

  8. Kashiwagi M, Tortorella M, Nagase H, Brew K (2001) TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4) and aggrecanase 2 (ADAM-TS5). J Biol Chem 276:12501–12504

    Article  CAS  PubMed  Google Scholar 

  9. Gao G, Westling J, Thompson VP (2002) Activation of the proteolytic activity of ADAMTS4 (aggrecanase-1) by C-terminal truncation. J Biol Chem 277:11034–11041

    Article  CAS  PubMed  Google Scholar 

  10. Porter S, Clark IM, Kevorkian L, Edwards DR (2005) The ADAMTS metalloproteinases. Biochem J 386:15–27

    Article  CAS  PubMed  Google Scholar 

  11. Sandy JD, Westling J, Kenagy RD (2002) Versican V1 proteolysis in human aorta in vivo occurs at the Glu441-Ala442 bond, a site that is cleaved by recombinant ADAMTS-1 and ADAMTS-4. J Biol Chem 276:13372–13378

    Article  Google Scholar 

  12. Apte SS, Olsen BR, Murphy G (1995) The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and its inhibitory activities define the distinct TIMP gene family. J Biol Chem 270:14313–14318

    Article  CAS  PubMed  Google Scholar 

  13. Naito S, Shiomi T, Okada A, Kimura T, Chijiiwa M, Fujita Y, Yatabe T, Komiya K, Enomoto H, Fujikawa K, Okada Y (2007) Expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic cartilage. Pathol Int 57(11):703–711

    Article  CAS  PubMed  Google Scholar 

  14. Wågsäter D, Björk H, Zhu C, Björkegren J, Valen G, Hamsten A (2008) ADAMTS-4 and -8 are inflammatory regulated enzymes expressed in macrophage-rich areas of human atherosclerotic plaques. Atherosclerosis 196:514–522

    Article  PubMed  Google Scholar 

  15. Galis ZS, Khatri JJ (2002) Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res 90:251–262

    CAS  PubMed  Google Scholar 

  16. Worley JR, Baugh MD, Hughes DA, Edwards DR, Hogan A, Sampson MJ, Gavrilovic J (2003) Metalloproteinase Expression in PMA-stimulated THP-1 Cells effects of peroxisome proliferator-activated receptor-γ (PPARγ) agonists and 9-cis-retinoic acid. J Biol Chem 51:51340–51346

    Article  Google Scholar 

  17. Goldstein JA, Demetriou D, Grines CL, Pica M, Shoukfeh M, O’Neill WW (2000) Multiple complex coronary plaques in patients with acute myocardial infarction. N Engl J Med 28:915–922

    Article  Google Scholar 

  18. Wysocki LJ, Sato VL (1978) “sPanning” for lymphocytes: a method for cell selection. Proc Natl Acad Sci USA 75:2844–2848

    Article  CAS  PubMed  Google Scholar 

  19. Hoover ML, Chapman SW, Cuchens MA (1985) A procedure for the isolation of highly purified populations of B cells, T cells and monocytes from human peripheral and umbilical cord blood. J Immunol Methods 78:71–85

    Article  CAS  PubMed  Google Scholar 

  20. Kaski JC, Chester MR, Chen L, Katritsis D (1995) Rapid angiographic progression of coronary artery disease in patients with angina pectoris:the role of complex stenosis morphology. Circulation 92:2058–2065

    CAS  PubMed  Google Scholar 

  21. Margolis RU, Margolis RK (1994) Aggrecan-versican-neurocan family of proteoglycans. Methods Enzymol 245:105–126

    Article  CAS  PubMed  Google Scholar 

  22. Yamagata M, Saga S, Kato M, Bernfield M, Kimata K (1993) Selective distributions of proteoglycans and their ligands in pericellular matrix of cultured fibroblasts: implications for their roles in cell-substratum adhesion. J Cell Sci 106:55–65

    CAS  PubMed  Google Scholar 

  23. Halpert I, Sires UI, Roby JD, Potter-Perigo S, Wight TN, Shapiro SD, Welgus HG, Wickline SA, Parks WC (1996) Matrilysin is expressed by lipid-laden macrophages at sites of potential rupture in atherosclerotic lesions and localizes to areas of versican deposition, a proteoglycan substrate for the enzyme. Proc Natl Acad Sci USA 93:9748–9753

    Article  CAS  PubMed  Google Scholar 

  24. Evanko SP, Raines EW, Ross R, Gold LI, Wight TN (1998) Proteoglycan distribution in lesions of atherosclerosis depends on lesion severity, structural characteristics, and the proximity of platelet-derived growth factor and transforming growth factor-beta. Am J Pathol 152:533–546

    CAS  PubMed  Google Scholar 

  25. Lemire JM, Braun KR, Maurel P, Kaplan ED, Schwartz SM, Wight TN (1999) Versican/PG-M Isoforms in Vascular Smooth Muscle Cells. Arterioscler Thromb Vasc Biol 19:1630–1639

    CAS  PubMed  Google Scholar 

  26. Sandy JD, Westling J, Kenagy RichardD, Iruela-Arispe ML, Verscharen C (2001) Versican V1 proteolysis in human aorta in vivo occurs at the Glu441-Ala442 bond, a site that is cleaved by recombinant ADAMTS-1 and ADAMTS-4. J Biol Chem 276:13372–13378

    Article  CAS  PubMed  Google Scholar 

  27. Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circulation 105:1135–1143

    Article  CAS  PubMed  Google Scholar 

  28. Brauer PR (2006) MMPs—role in cardiovascular development and disease. Front Biosci 11:447–478

    Article  CAS  PubMed  Google Scholar 

  29. Whatling C, Bjork H, Gredmark S, Hamsten A, Eriksson P (2004) Effect of macrophage differentiation and exposure to mildly oxidized LDL on the proteolytic repertoire of THP-1 monocytes. J Lipid Res 45:1768–1776

    Article  CAS  PubMed  Google Scholar 

  30. Jude B, Agraou B, McFadden EP (1994) Evidence for time-dependent activation of monocytes in the systemic circulation in unstable angina but not in acute myocardial infarction or in stable angina. Circulation 90:1662–1668

    CAS  PubMed  Google Scholar 

  31. Divies MJ (1996) Stability and instability: two faces of coronary atherosclerosis. Circulation 94:2013–2020

    Google Scholar 

  32. Schroeder AP, Falk E (1995) Vulnerable and dangerous coronary plaques. Atherosclerosis 118:S141–S149

    Article  CAS  PubMed  Google Scholar 

  33. Wilson RF, Holida MD, White CW (1986) Quantitative angiographic morphology of coronary stenoses leading to myocardial infarction or unstable angina. Circulation 73:286–293

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Dr. Lianqun Cui for his critical review on this manuscript. We also thank participants, general practitioners and staff members in the Department of Cardiology as well as the support from Central Research Laboratories at our institution.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lianqun Cui.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zha, Y., Chen, Y., Xu, F. et al. Elevated level of ADAMTS4 in plasma and peripheral monocytes from patients with acute coronary syndrome. Clin Res Cardiol 99, 781–786 (2010). https://doi.org/10.1007/s00392-010-0183-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-010-0183-1

Keywords