Vol 26, No 4 (2019)
Original articles — Basic science and experimental cardiology
Published online: 2018-03-26

open access

Page views 5109
Article views/downloads 1339
Get Citation

Connect on Social Media

Connect on Social Media

Increased plasma cathepsin S and trombospondin-1 in patients with acute ST-segment elevation myocardial infarction

Rahel Befekadu1, Kjeld Christiansen2, Anders Larsson3, Magnus Grenegård4
Pubmed: 29611169
Cardiol J 2019;26(4):385-393.


Background: The role of cathepsins in the pathological progression of atherosclerotic lesions in ischem­ic heart disease have been defined in detail more than numerous times. This investigation examined the platelet-specific biomarker trombospondin-1 (TSP-1) and platelet function ex vivo, and compared this with cathepsin S (Cat-S; a biomarker unrelated to platelet activation but also associated this with increased mortality risk) in patients with ST-segment elevation myocardial infarction (STEMI).

Methods: The STEMI patients were divided into two groups depending on the degree of coronary vessel occlusion: those with closed (n = 90) and open culprit vessel (n = 40). Cat-S and TSP-1 were analyzed before, 1–3 days after and 3 months after percutanous coronary intervention (PCI).

Results: During acute STEMI, plasma TSP-1 was significantly elevated in patients with closed cul­prit lesions, but rapidly declined after PCI. In fact, TSP-1 after PCI was significantly lower inpatient samples compared to healthy individuals. In comparison, plasma Cat-S was significantly elevated both before and after PCI. In patients with closed culprit lesions, Cat-S was significantly higher compared to patients with open culprit lesions 3 months after PCI. Although troponin-I were higher (p < 0.01) in patients with closed culprit lesion, there was no correlation with Cat-S and TSP-1.

Conclusions: Cat-S but not TSP-1 may be a useful risk biomarker in relation to the severity of STEMI. However, the causality of Cat-S as a predictor for long-term mortality in STEMI remains to be ascertained in future studies.

Article available in PDF format

View PDF Download PDF file


  1. Li X, Liu Z, Cheng Z, et al. Cysteinyl cathepsins: multifunctional enzymes in cardiovascular disease. Chonnam Med J. 2012; 48(2): 77–85.
  2. Reiser J, Adair B, Reinheckel T. Specialized roles for cysteine cathepsins in health and disease. J Clin Invest. 2010; 120(10): 3421–3431.
  3. Turk V, Stoka V, Vasiljeva O, et al. Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochim Biophys Acta. 2012; 1824(1): 68–88.
  4. Cheng XWu, Shi GP, Kuzuya M, et al. Role for cysteine protease cathepsins in heart disease: focus on biology and mechanisms with clinical implication. Circulation. 2012; 125(12): 1551–1562.
  5. Kirschke H, Wiederanders B, Brömme D, et al. Cathepsin S from bovine spleen. Purification, distribution, intracellular localization and action on proteins. Biochem J. 1989; 264(2): 467–473.
  6. Cheng XWu, Huang Z, Kuzuya M, et al. Cysteine protease cathepsins in atherosclerosis-based vascular disease and its complications. Hypertension. 2011; 58(6): 978–986.
  7. Hsing LC, Rudensky AY. The lysosomal cysteine proteases in MHC class II antigen presentation. Immunol Rev. 2005; 207: 229–241.
  8. Liu W, Spero DM. Cysteine protease cathepsin S as a key step in antigen presentation. Drug News Perspect. 2004; 17(6): 357–363.
  9. Lutgens SPM, Cleutjens KB, Daemen MJ, et al. Cathepsin cysteine proteases in cardiovascular disease. FASEB J. 2007; 21(12): 3029–3041.
  10. Pan L, Li Y, Jia L, et al. Cathepsin S deficiency results in abnormal accumulation of autophagosomes in macrophages and enhances Ang II-induced cardiac inflammation. PLoS One. 2012; 7(4): e35315.
  11. Taleb S, Lacasa D, Bastard JP, et al. Cathepsin S, a novel biomarker of adiposity: relevance to atherogenesis. FASEB J. 2005; 19(11): 1540–1542.
  12. Qin Y, Yang Y, Liu R, et al. Combined Cathepsin S and hs-CRP predicting inflammation of abdominal aortic aneurysm. Clin Biochem. 2013; 46(12): 1026–1029.
  13. de Nooijer R, Bot I, von der Thüsen JH, et al. Leukocyte cathepsin S is a potent regulator of both cell and matrix turnover in advanced atherosclerosis. Arterioscler Thromb Vasc Biol. 2009; 29(2): 188–194.
  14. Ambily A, Kaiser WJ, Pierro C, et al. The role of plasma membrane STIM1 and Ca(2+)entry in platelet aggregation. STIM1 binds to novel proteins in human platelets. Cell Signal. 2014; 26(3): 502–511.
  15. Ji K, de Carvalho LP, Bi X, et al. Highly sensitive and quantitative human thrombospondin-1 detection by an M55 aptasensor and clinical validation in patients with atherosclerotic disease. Biosens Bioelectron. 2014; 55: 405–411.
  16. Marmagkiolis K, Feldman DN, Charitakis K. Thrombus Aspiration in STEMI. Curr Treat Options Cardiovasc Med. 2016; 18(1): 7.
  17. Wachtell K, Lagerqvist Bo, Olivecrona GK, et al. Novel Trial Designs: Lessons Learned from Thrombus Aspiration During ST-Segment Elevation Myocardial Infarction in Scandinavia (TASTE) Trial. Curr Cardiol Rep. 2016; 18(1): 11.
  18. Soon K, Du HN, Klim S, et al. Non-ST elevation myocardial infarction with occluded artery and its clinical implications. Heart Lung Circ. 2014; 23(12): 1132–1140.
  19. Rodgers KJ, Watkins DJ, Miller AL, et al. Destabilizing role of cathepsin S in murine atherosclerotic plaques. Arterioscler Thromb Vasc Biol. 2006; 26(4): 851–856.
  20. Galon MZ, Wang Z, Bezerra HG, et al. Differences determined by optical coherence tomography volumetric analysis in non-culprit lesion morphology and inflammation in ST-segment elevation myocardial infarction and stable angina pectoris patients. Catheter Cardiovasc Interv. 2015; 85(4): E108–E115.
  21. Ellulu MS, Patimah I, Khaza'ai H, et al. Atherosclerotic cardiovascular disease: a review of initiators and protective factors. Inflammopharmacology. 2016; 24(1): 1–10.
  22. Goel S, Miller A, Agarwal C, et al. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque. Radiol Res Pract. 2015; 2015: 410967.
  23. Lv BJ, Lindholt JS, Cheng X, et al. Plasma cathepsin S and cystatin C levels and risk of abdominal aortic aneurysm: a randomized population-based study. PLoS One. 2012; 7(7): e41813.
  24. Chatzizisis YS, Baker AB, Sukhova GK, et al. Augmented expression and activity of extracellular matrix-degrading enzymes in regions of low endothelial shear stress colocalize with coronary atheromata with thin fibrous caps in pigs. Circulation. 2011; 123(6): 621–630.
  25. Steubl D, Kumar SV, Tato M, et al. Circulating cathepsin-S levels correlate with GFR decline and sTNFR1 and sTNFR2 levels in mice and humans. Sci Rep. 2017; 7: 43538.
  26. Yan L, Ding S, Gu B, et al. Clinical application of simultaneous detection of cystatin C, cathepsin S, and IL-1 in classification of coronary artery disease. J Biomed Res. 2017; 31(4): 315–320.
  27. Leung LL. Role of thrombospondin in platelet aggregation. J Clin Invest. 1984; 74(5): 1764–1772.
  28. Vyas A, El Accaoui R, Blevins A, et al. Outcome comparison of 600 mg versus 300 mg loading dose of clopidogrel for patients with ST-elevation myocardial infarction: a meta-analysis. Postgrad Med. 2014; 126(5): 176–186.
  29. Wilhelmsen L. [ISIS-2--a study of patients with myocardial infarction. A combination of streptokinase and acetylsalicylic acid diminishes mortality risk, reinfarction and stroke]. Lakartidningen. 1988; 85(35): 2759–2764.
  30. Baigent C, Collins R, Appleby P, et al. ISIS-2: 10 year survival among patients with suspected acute myocardial infarction in randomised comparison of intravenous streptokinase, oral aspirin, both, or neither. The ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. BMJ. 1998; 316(7141): 1337–1343.
  31. Holmes MV, Perel P, Shah T, et al. CYP2C19 genotype, clopidogrel metabolism, platelet function, and cardiovascular events: a systematic review and meta-analysis. JAMA. 2011; 306(24): 2704–2714.
  32. Grenegård M, Vretenbrant-Oberg K, Nylander M, et al. The ATP-gated P2X1 receptor plays a pivotal role in activation of aspirin-treated platelets by thrombin and epinephrine. J Biol Chem. 2008; 283(27): 18493–18504.