CC BY-NC-ND 4.0 · J Lab Physicians 2022; 14(03): 253-259
DOI: 10.1055/s-0042-1742418
Original Article

Association of Serum Cyclophilin A Levels with Severity of Coronary Artery Disease

1   Department of Biochemistry, ESIC Medical College and Hospital, Hyderabad, Telangana, India
Neelam N. Sreedevi
2   Department of Biochemistry, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
Sabitha Thummala
2   Department of Biochemistry, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
Kompella S.S. Saibaba
2   Department of Biochemistry, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
2   Department of Biochemistry, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
Oruganti Sai Satish
3   Department of Cardiology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
› Author Affiliations
Funding This study was self-funded.


Objective The disequilibrium between oxidant and antioxidant systems causes oxidative stress. Further, it disrupts the cell and releases reactive oxygen species (ROS), which in turn damages the vascular functions. Cyclophilin A (CypA), an immunophilin, is released in a highly regulated manner from vascular smooth muscle cells and multiplies the deleterious effects of ROS, associated with cardiovascular diseases. Thus, the aim of the present study is to correlate serum CypA levels with the severity of coronary artery disease (CAD).

Materials and Methods Study participants composed of 103 adult subjects, among whom 73 subjects were cases who were diagnosed as CAD angiographically. Thirty years of age and gender-matched subjects were taken as controls. The cases were further divided into single, double, and triple vessel disease subgroups. Blood samples were collected for the estimation of serum CypA, malondialdehyde (MDA), high-sensitive C-reactive protein (hsCRP), lipid profile, and plasma-glycated hemoglobin (HbA1C) by relevant biochemical methods.

Statistical Analysis The analysis was done using SPSS version 25. The data were expressed as median/mean and interquartile range/standard error. The groups were compared using the Mann–Whitney U-test and the Kruskal–Wallis test. p-Value less than 0.05 was considered statistically significant. Comparison of area under the curve (AUC) in receiver operating characteristic (ROC) curves was performed. A correlation was done by Spearman rank correlation.

Results The mean levels of serum CypA, hsCRP, and MDA in cases were significantly higher than those of controls (38 vs. 27 ng/mL, 18 vs. 5.1 mg/L, and 26 vs. 14 nmol/mL, p < 0.001). A positive correlation was observed between serum levels of CypA versus hsCRP and CypA versus MDA (r = 0.36 p = 0.00, r = 0.52, p = 0.00). At cut-off values greater than 33 ng/mL and 2.1 mg/L, serum CypA and hsCRP have 71% sensitivity, 93% specificity (AUC = 0.83), 84% sensitivity, and 70% specificity (AUC = 0.78) respectively. The number of occluded vessels was positively correlated with both CypA and hsCRP. Also, Serum CypA showed a significant positive correlation with HbA1C.

Conclusion Serum CypA can be used as a valuable biomarker for CAD.

Ethical Clearance

The study was approved by the hospital's institutional ethical committee (EC/NIMS/1673/2015).

Publication History

Article published online:
15 February 2022

© 2022. The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (

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  • References

  • 1 Krishnan MN. Coronary heart disease and risk factors in India - on the brink of an epidemic?. Indian Heart J 2012; 64 (04) 364-367
  • 2 Herrington W, Lacey B, Sherliker P, Armitage J, Lewington S. Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circ Res 2016; 118 (04) 535-546
  • 3 Bhat MA, Mahajan N, Gandhi G. Oxidative stress status in coronary artery disease patients. IJLBPR 2012; 1: 2250-3137
  • 4 Suzuki J, Jin ZG, Meoli DF, Matoba T, Berk BC. Cyclophilin A is secreted by a vesicular pathway in vascular smooth muscle cells. Circ Res 2006; 98 (06) 811-817
  • 5 Satoh K, Fukumoto Y, Sugimura K. et al. Plasma cyclophilin A is a novel biomarker for coronary artery disease. Circ J 2013; 77 (02) 447-455
  • 6 Jin ZG, Melaragno MG, Liao DF. et al. Cyclophilin A is a secreted growth factor induced by oxidative stress. Circ Res 2000; 87 (09) 789-796
  • 7 Tristano AG, Castejon AM, Castro A, Cubeddu LX. Effects of statin treatment and withdrawal on angiotensin II-induced phosphorylation of p38 MAPK and ERK1/2 in cultured vascular smooth muscle cells. Biochem Biophys Res Commun 2007; 353 (01) 11-17
  • 8 Pan H, Luo C, Li R. et al. Cyclophilin A is required for CXCR4-mediated nuclear export of heterogeneous nuclear ribonucleoprotein A2, activation and nuclear translocation of ERK1/2, and chemotactic cell migration. J Biol Chem 2008; 283 (01) 623-637
  • 9 Zhu C, Wang X, Deinum J. et al. Cyclophilin A participates in the nuclear translocation of apoptosis-inducing factor in neurons after cerebral hypoxia-ischemia. J Exp Med 2007; 204 (08) 1741-1748
  • 10 Nigro P, Pompilio G, Capogrossi MC. Cyclophilin A: a key player for human disease. Cell Death Dis 2013; 4 (10) e888-e888
  • 11 Satoh K, Matoba T, Suzuki J. et al. Cyclophilin A mediates vascular remodeling by promoting inflammation and vascular smooth muscle cell proliferation. Circulation 2008; 117 (24) 3088-3098
  • 12 Satoh K, Nigro P, Matoba T. et al. Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II-induced aortic aneurysms. Nat Med 2009; 15 (06) 649-656
  • 13 Weintraub NL. Understanding abdominal aortic aneurysm. N Engl J Med 2009; 361 (11) 1114-1116
  • 14 Nigro P, Satoh K, O'Dell MR. et al. Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in apolipoprotein E-deficient mice. J Exp Med 2011; 208 (01) 53-66
  • 15 Rezzani R, Favero G, Stacchiotti A, Rodella LF. Endothelial and vascular smooth muscle cell dysfunction mediated by cyclophylin A and the atheroprotective effects of melatonin. Life Sci 2013; 92 (17–19): 875-882
  • 16 Seizer P, Schönberger T, Schött M. et al. EMMPRIN and its ligand cyclophilin A regulate MT1-MMP, MMP-9 and M-CSF during foam cell formation. Atherosclerosis 2010; 209 (01) 51-57
  • 17 Zaki MM, Mohsen M, Shaaban MA, Sedky RM. Study of serum levels of cyclophilin A in patients with coronary artery disease. QJM: Int J Med 2020; 113 (Issue Suppl 1): hcaa061.002
  • 18 Hussain M, Mohammed E, El-Sherbeny A, Shehata A. Cyclophilin A: a novel biomarker for cardiovascular disease in patients with type 2 diabetes. Egypt J Intern Med 2019; 31 (04) 416
  • 19 Ohtsuki T, Satoh K, Omura J. et al. Prognostic impacts of plasma levels of cyclophilin A in patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2017; 37 (04) 685-693
  • 20 Alfonso A, Bayón J, Gegunde S. et al. High serum cyclophilin C levels as a risk factor marker for coronary artery disease. Sci Rep 2019; 9 (01) 10576
  • 21 Yan J, Zang X, Chen R. et al. The clinical implications of increased cyclophilin A levels in patients with acute coronary syndromes. Clin Chim Acta 2012; 413 (7–8): 691-695
  • 22 Jin ZG, Lungu AO, Xie L, Wang M, Wong C, Berk BC. Cyclophilin A is a proinflammatory cytokine that activates endothelial cells. Arterioscler Thromb Vasc Biol 2004; 24 (07) 1186-1191
  • 23 Vinitha A, Kutty VR, Vivekanand A. et al. PPIA rs6850: A > G single-nucleotide polymorphism is associated with raised plasma cyclophilin A levels in patients with coronary artery disease. Mol Cell Biochem 2016; 412 (1–2): 259-268
  • 24 Yossef AA, Issa HA, Ahmad ES, Farag SE, Abd El Bar NA. Assessment of plasma level of cyclophilin A in type 2 diabetic patients suffering from vascular diseases. Benha Med J 2018; 35 (02) 188-193
  • 25 Noshin TF, Ali MR, Banik S. Increased oxidative stress and altered serum macro-minerals and trace elements levels are associated with coronary artery disease. J Trace Elem Med Biol 2021; 64: 126707
  • 26 Khaki Khatibi F, Yaghoubi A, Zarghami N, Rahbani M, Babaei H. Evaluation of hs-CRP, antioxidant markers and MDA in patients of coronary artery disease (CAD) containing non-smokers and non-diabetics. J Cardiovasc Thorac Res 2011; 2: 13-18
  • 27 Uppal N, Uppal V, Uppal P. Progression of coronary artery disease (CAD) from stable angina (SA) towards myocardial infarction (MI): role of oxidative stress. J Clin Diagn Res 2014; 8 (02) 40-43
  • 28 Mutlu-Türkoğlu U, Akalin Z, Ilhan E. et al. Increased plasma malondialdehyde and protein carbonyl levels and lymphocyte DNA damage in patients with angiographically defined coronary artery disease. Clin Biochem 2005; 38 (12) 1059-1065
  • 29 Stocker R, Keaney Jr JF. Role of oxidative modifications in atherosclerosis. Physiol Rev 2004; 84 (04) 1381-1478
  • 30 Guruprasad S, Rajasekhar D, Subramanyam G, Srinivasa Rao PVLN, Vanajakshamma V, Latheef K. High sensitivity C-reactive protein levels across spectrum and severity of coronary artery disease. J Clin Sci Res 2012; 1 (03) 126-130
  • 31 Rashidinejad H, Moazanzadeh M, Mirshekarpoor H, Ebrahimi F. The relationship between HS-CRP serum levels with the results of cardiac perfusion SPECT imaging in patients with suspected coronary artery disease. Asian J Biomed Pharm Sci 2015; 5 (50) 30-33
  • 32 Ramachandran S, Venugopal A, Kutty VR. et al. Plasma level of cyclophilin A is increased in patients with type 2 diabetes mellitus and suggests presence of vascular disease. Cardiovasc Diabetol 2014; 13 (01) 38