Plasma granzyme B as a predicting factor of coronary artery disease--clinical significance in patients with chronic renal failure.
OBJECTIVE
To elucidate the role of granzyme B in coronary artery disease (CAD) in patients with chronic kidney disease (CKD). We hypothesized that granzyme B plays an important role in the formation of coronary artery lesions in patients with CKD.


METHODS
We studied 141 patients (116 men and 25 women; mean age, 64.2±9.6 years) and 16 control subjects. Diagnosis of CAD was confirmed by selective coronary angiography. CKD was defined as a sustained decrease in the estimated glomerular filtration (eGFR) rate less than 60 mL/min/1.73 m(2) over 3 months. We assigned patients to three groups: CAD without CKD (CAD group, n=46), CKD without CAD (CKD group, n=18), and CAD with CKD (CAD/CKD group, n=77). Plasma granzyme B was measured by enzyme-linked immunosorbent assay. Factors contributing to the severity of CAD were analyzed by multiple regression analysis in patients with CAD.


RESULTS
Plasma levels of high-sensitivity CRP (hs-CRP) and granzyme B in the CAD/CKD group were significantly higher than in other groups. A significant positive correlation was observed between plasma hs-CRP and granzyme B levels. A significant negative correlation was observed between eGFR and granzyme B levels. Multiple regression analysis revealed that granzyme B and hs-CRP levels were independent predicting variables of the number of stenoses in major coronary arteries.


CONCLUSIONS
These results indicate that granzyme B might be a novel risk factor for the formation of coronary atherosclerosis by inducing apoptosis of vascular tissues in patients with CKD.
Ikemoto
Tomokazu
T
Department of Cardiology, Jichi Medical University, 3311 Yakushiji, Shimotsuke-City, Tochigi 329-0498, Japan.
Hojo
Yukihiro
Y
Kondo
Hideyuki
H
Takahashi
Nozomu
N
Hirose
Masahiro
M
Nishimura
Yoshioki
Y
Katsuki
Takaaki
T
Shimada
Kazuyuki
K
D000368:Aged; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000209:etiology* / Q000473:pathology; D003331:Coronary Vessels / Q000166:cytology / Q000473:pathology; D005260:Female; D005919:Glomerular Filtration Rate; D053804:Granzymes / Q000097:blood* / Q000502:physiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012044:Regression Analysis; D012307:Risk Factors; D012720:Severity of Illness Index
D015415:Biomarkers; D002097:C-Reactive Protein; D053804:Granzymes