Abstract 3711: Increased Expression of Plasma Granzyme B in the Patients with Coronary Artery Disease Complicated with Chronic Kidney Disease
Background: Recent clinical studies have revealed that chronic kidney disease (CKD) is a significant independent risk factor for major cardiovascular events. However, the mechanisms in which CKD increases the incidence of cardiovascular diseases are still not fully understood.
Hypothesis: Granzyme B is a member of serine protease family released from cytotoxic T lymphocytes and plays an important role in cellular apoptosis via an activation of caspases. We hypothesized that granzyme B is involved in formation of coronary artery lesions in patients with CKD.
Objectives: To elucidate the role of granzyme B in coronary artery disease (CAD) in patients complicated with CKD.
Subjects and methods: We employed 141 patients (116 men and 25 women, mean age: 64.2±9.6 years old ). Diagnosis of CAD was confirmed by selective coronary angiography. CKD was defined as sustained decrease in estimated glomerular filtration rate less than 60 mL/min/1.73m2 over 3 months. We assigned patients into three groups; CAD without CKD (CAD group, n=46), CKD without CAD (CKD group, n=17) and CAD with CKD (CAD/CKD group, n=78). Patients with acute coronary syndrome, immunological disorder, malignancy and acute inflammatory diseases were excluded from the study.
Results: Analysis of variance showed that plasma levels of high-sensitive CRP (hsCRP) and granzyme B in CAD/CKD group were significantly higher than those in the other groups (hsCRP: CAD; 2420±763, CKD; 1802±584, CAD/CKD: 7419±2171 ng/mL, p<0.05, granzyme B: CAD: 9.1±2.3, CKD: 42.2±2.4, CAD/CKD: 159±51.8 pg/mL, p<0.01). A significant positive correlation was observed between plasma hsCRP and granzyme B levels (r=+0.30, p<0.05). A significant negative correlation was observed between eGFR and granzyme B levels (r=−0.32, p<0.01). Multiple regression analysis revealed that granzyme B and hs CRP levels were independent predicting variables for the number of stenosis in major coronary arteries (F=5.35, p=0.002, beta coefficients: granzyme B=+0.24, p=0.006, hsCRP=+0.18, p=0.03).
Conclusions: These results indicate that granzyme B might be a critical enzyme for formation of coronary atherosclerosis by inducing apoptosis of vascular tissues in patients with CKD.