Fig 2: Receiver-operating-characteristic curves (ROC) describing the diagnostic performance of cyclophilins to identify coronary artery disease (CAD) > 50% as compared with the control subjects. (A) Cyclophilin A (CypA), the AUC (c-statistic) was 0.748 (95% confidence interval (CI), 0.654–0.851, p < 0.001). (B) Cyclophilin B (CypB), the AUC (c-statistic) was 0.655 (95% CI, 0.538–0.773, p = 0.014). (C) Cyclophilin C (CypC), the AUC (c-statistic) was 0.891 (95% CI, 0.821–0.961, p < 0.001), Specificity (88.6%), Sensitivity (70%), positive predictive value (VPP) (84.8%) and negative predictive value (VPN) (76%). (D) Cyclophilin D (CypD) the AUC (c-statistic) was 0.526 (95% CI, 0.396–0.655, p = 0.687). N = 84.

Fig 3: Effect of compounds 1, 2, and GraL over intra and extracellular CypA, B and C levels in human T lymphocytes stimulated with Con A Cells were pre-treated with compound 1, 2 (0.1 µM), GraL (1 µM) or CsA (0.2 µM) for 2 h and then were stimulated with Con A (50 µg/mL) for 48 h. CypA (A), CypB (B), and CypC (C) levels were measured by ELISA in the medium of T lymphocytes. The line represents the unstimulated cells values. The intracellular expression of CypA (D), CypB (E), and CypC (F) was measured by western blot in cytosolic lysates of T lymphocytes. Band intensity was normalized by ß-actin. Data are the result of average ± SEM (n = 3). The values are shown as the difference between cells treated with Con A and cells treated with compounds plus Con A, *p < 0.05, **p < 0.01 and ***p < 0.001. Values of cells treated with Con A were compared with control cells, # p < 0.05, ## p < 0.01 and ### p < 0.001. One-way ANOVA test with Dunnet’s post hoc analysis and Student´s t-test were used for statistical analysis.

Fig 4: Serum Crps levels ((a) CypA, (b) CrpB, (c) CypC, (d) CypD) in patients with CAD and the relationship with traditional cardiovascular risk factors. Frequency plots: data represented as Cyp levels in x-axis, versus traditional cardiovascular risk factors (hypertension, dyslipidemia, smoking, gender, diabetes and age > 50 years) in y-axis. CAD: coronary artery disease; Crps: cyclophilins.

Fig 5: Area under the curve of CypC = 17.5 pg/mL at baseline, at 6 months, and at 12 months. AUC-COR: area under the curve; 95% CI AUC: 95% confidence interval area under the curve; NPV: negative predictive value; PPV: positive predictive value.