Novel Biomarkers for Cardiac Hypertrophy, Fibrosis and Failure: Cyclophilin A and Basigin—Clinical Application of Basic Research-

We have recently demonstrated that cyclophilin A (CyPA) is secreted from cardiac fibroblasts in response to several stimuli including angiotensin II and mechanical stretch, and promotes cardiac hypertrophy, fibrosis and failure. Moreover, we have shown that basigin (Bsg) is one of the extracellular receptor for CyPA and promotes cell proliferation and inflammation, contributing to cardiac hypertrophy, fibrosis, inflammation and dysfunction. In a clinical study, we have demonstrated that plasma CyPA levels were significantly elevated in HF patients (15.3 ± 9.6 ng/mL, n = 123) than in healthy controls (5.2 ± 4.5 ng/mL, n = 20, P < .001). Kaplan-Meier curve showed that higher CyPA levels (>15 ng/mL) were associated with all-cause death (HR3.7, P < .05) and rehospitalization (HR3.0, P < .05). Importantly, the combination of CyPA (>15 ng/mL) and BNP (>100 pg/mL) was highly significantly associated with all-cause death (HR12.5, P < .05) and rehospitalization (HR10.1, P < .01) compared with CyPA (>15 ng/mL) or BNP (>100 pg/mL) alone. In a separate clinical study, serum soluble Bsg (sBsg) levels were also significantly elevated in patients with heart failure (n = 187) compared with healthy controls (n = 12) (3730 ± 321 vs. 2068 ± 149 pg/ml, P < .01). Furthermore, high serum sBsg levels (cut-off point, >3,099 pg/ml) was significantly associated with poor prognosis in heart failure patients (P < .01). These results indicate that plasma levels of CyPA and sBsg have prognostic impacts in HF patients, which are further enhanced when combined with BNP.