Background: We tested the hypothesis that increased levels of cathepsin S and decreased levels of cystatin C in plasma at the time of percutaneous transluminal angioplasty (PTA) are associated with the occurrence of 6-months’ restenosis of the femoropopliteal artery (FPA). Methods: 20 patients with restenosis and 24 matched patients with patent FPA after a 6-months follow-up were in - cluded in this study. They all exhibited disabling claudication or critical limb ischemia and had undergone technically successful PTA. They were all receiving statins and ACE in hi - bitors (or angiotensin II receptor antagonist) before the PTA and the therapy did not change throughout the observational period. Plasma concentrations of C-reactive protein were < 10 mg/L and of creatinine within the reference range at the time of the PTA. Plasma concentration and activity of cathepsin S, together with its potent inhibitor cystatin C, were measured the day before and the day after the PTA. Results: The increased plasma concentration and activity of cathepsin S at the time of PTA was associated with the occurrence of 6-months’ restenosis of FPA, independently of established risk factors (lesion complexity, infrapopliteal run-off vessels, type of PTA, age, gender, smoking, diabetes, lipids) and of cystatin C. Plasma cystatin C concentration was not associated with restenosis and did not correlate with cathepsin S activity and concentration in the plasma. Conclusion: Increased level of plasma cathepsin S at the time of PTA is associated with 6-months’ restenosis of PTA, independently of established risk factors.
1. Pentecost MJ, Criqui MH, Dorros G, Goldstone J, Johnston KW, Martin EC, et al. Guidelines for peripheral percutaneous transluminal angioplasty of the abdominal aorta and lower extremity vessels. A statement for health professionals from a Special Writing Group of the Councils on Cardiovascular Radiology, Arteriosclerosis, Cardio-Thoracic and Vascular Surgery, Clinical Cardiol - ogy, and Epidemiology and Prevention, the American Heart Association. J Vasc Interv Radiol 2003; 14: S495-15.
2. Clark TW, Groffsky JL, Soulen MC. Predictors of longterm patency after femoropopliteal angioplasty: results from the STAR registry. J Vasc Interv Radiol 2001; 12: 923-33.
3. Muradin GS, Bosch JL, Stijnen T, Hunink MG. Balloon dilation and stent implantation for treatment of femoro - popliteal arterial disease: meta-analysis. Radiology 2001; 221: 137-45.
4. Schillinger M, Minar E. Restenosis after percutaneous angioplasty: the role of vascular inflammation. Vasc Health Risk Manag 2005; 1: 73-8.
5. Cheng XW, Huang Z, Kuzuya M, Okumura K, Murohara T. Cysteine protease cathepsins in atherosclerosisbased vascular disease and its complications. Hyper - tension 2011; 58: 978-86.
6. Sukhova GK, Shi GP, Simon DI, Chapman HA, Libby P. Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells. J Clin Invest 1998; 102: 576-83.
7. Lutgens SP, Cleutjens KB, Daemen MJ, Heeneman S. Cathepsin cysteine proteases in cardiovascular disease. FASEB J 2007; 21: 3029-41.
8. Sukhova GK, Zhang Y, Pan JH, Wada Y, Yamamoto T, Naito M, et al. Deficiency of cathepsin S reduces atherosclerosis in LDL receptor-deficient mice. J Clin Invest 2003; 111: 897-906.
9. de Nooijer R, Bot I, von der Thusen JH, Leeuwenburgh MA, Overkleeft HS, Kraaijeveld AO, et al. Leukocyte cathepsin S is a potent regulator of both cell and matrix turnover in advanced atherosclerosis. Arterioscler Thromb Vasc Biol 2009; 29: 188-94.
10. Rodgers KJ, Watkins DJ, Miller AL, Chan PY, Karanam S, Brissette WH, et al. Destabilizing role of cathepsin S in murine atherosclerotic plaques. Arterioscler Thromb Vasc Biol 2006; 26: 851-6.
11. Liu J, Ma L, Yang J, Ren A, Sun Z, Yan G, et al. Increased serum cathepsin S in patients with atherosclerosis and diabetes. Atherosclerosis 2006; 186: 411-9.
12. Cerne D, Stern I, Marc J, Cerne A, Zorman D, Krzisnik- Zorman S, et al. CTSS activation coexists with CD40 activation in human atheroma: evidence from plasma mRNA analysis. Clin Biochem 2011; 44: 438-40.
13. Mirjanic-Azaric B, Vekic J, Zeljkovic A, Jelic-Ivanovic Z, Djeric M, Milivojac T, et al. Interrelated cathepsin S-lowering and LDL subclass profile improvements induced by atorvastatin in the plasma of stable angina patients. J Atheroscler Thromb 2014; 21: 868-77.
14. Salgado JV, Souza FL, Salgado BJ. How to understand the association between cystatin C levels and cardiovascular disease: Imbalance, counterbalance, or consequence? J Cardiol 2013; 62: 331-5.
15. Dandana A, Gammoudi I, Chalghoum A, Chahed H, Addad F, Ferchichi S, et al. Clinical utility of serum cystatin C in predicting coronary artery disease in patients without chronic kidney disease. J Clin Lab Anal 2014; 28: 191-7.
16. Zhao C, Yang L, Mao L, Zhong L, Li X, Wei S. Cystatin C associates with the prediction of in-stent restenosis among patients receiving stent implantation: results of the 1-year follow-up. Coron Artery Dis 2013; 24: 357-60.
17. Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 1997; 26: 517-38.
18. European Stroke Organisation, Tendera M, Aboyans V, Bartelink ML, Baumgartner I, Clement D, et al. ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC). Eur Heart J 2011; 32: 2851-906.
19. Kos J, Sekirnik A, Kopitar G, Cimerman N, Kayser K, Stremmer A, et al. Cathepsin S in tumours, regional lymph nodes and sera of patients with lung cancer: relation to prognosis. Brit J Cancer 2001; 85: 1193-200.
20. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, HarrisKA, Fowkes FG, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). Eur J Vasc Endovasc Surg 2007; 33 Suppl 1: S1-75.
21. Schillinger M, Exner M, Mlekusch W, Rumpold H, Ah - madi R, Sabeti S, et al. Vascular inflammation and percutaneous transluminal angioplasty of the femoropopliteal artery: association with restenosis. Radiology 2002; 225: 21-6.
22. Parmar JH, Aslam M, Standfield N. Percutaneous transluminal angioplasty of lower limb arteries causes a systemic inflammatory response. Ann Vasc Surg 2009; 23: 569-76.
23. Abisi S, Burnand KG, Humphries J, Waltham M, Taylor P, Smith A. Effect of statins on proteolytic activity in the wall of abdominal aortic aneurysms. Br J Surg 2008; 95: 333-7.
24. Stern I, Marc J, Kranjec I, Zorman D, Cerne A, Cerne D. Increased plasma levels of CATS mRNA but not CATB mRNA in patients with coronary atherosclerosis. Clin Biochem 2010; 43: 1427-30.
25. Qin YW, Ye P, He JQ, Sheng L, Wang LY, Du J. Sim - vastatin inhibited cardiac hypertrofi and fibrosis in apolipoprotein E-deficient mice fed a ≫Western-style diet≪ by increasing PPAR and expression and reducing TC, MMP-9, and Cat S levels. Acta Pharmacol Sin 2010; 31: 1350-8.
26. Suganuma E, Babaev VR, Motojima M, Zuo Y, Ayabe N, Fogo AB, et al. Angiotensin inhibition decreases progression of advanced atherosclerosis and stabilizes established atherosclerotic plaques. J Am Soc Nephrol 2007; 18: 2311-9.
27. Cheng XW, Murohara T, Kuzuya M, Izawa H, Sasaki T, Obata K, et al. Superoxide-dependent cathepsin activation is associated with hypertensive myocardial remodeling and represents a target for angiotensin II type 1 receptor blocker treatment. Am J Pathol 2008; 173: 358-69.
28. Niccoli G, Conte M, Della Bona R, Altamura L, Siviglia M, Dato I, et al. Cystatin C isassociated with an increased coronary atherosclerotic burden and a stable plaque phenotype in patients with ischemic heart disease and normal glomerular filtration rate. Atherosclerosis 2008; 198: 373-80.
29. McDermott MM, Lloyd-Jones DM. The role of biomarkers and genetics in peripheral arterial disease. J Am Coll Cardiol 2009; 54: 1228-37.