Protein Z-dependent protease inhibitor and protein Z in peripheral arterial disease patients.
OBJECTIVE
Protein Z is a vitamin K-dependent protein that serves as a cofactor for the inhibition of activated factor X by the serpin protein Z-dependent protease inhibitor (ZPI). Protein Z plasma levels have been shown to be reduced in patients with peripheral arterial disease (PAD), but ZPI levels have not yet been reported. The aim of this study was to more fully assess the protein Z-ZPI system in individuals with atherosclerosis selected by the presence of symptomatic PAD.


METHODS
Protein Z and ZPI levels were determined in 95 PAD patients (73 males; 22 females) [median age: 73 years (range, 50-86 years)] and in 190 controls comparable for age and gender. Protein Z was measured using a commercial immunoassay, and ZPI was measured with a homemade immunoassay and a functional assay.


RESULTS
Protein Z antigen, ZPI antigen and ZPI function were found to be significantly lower in PAD patients with respect to controls [protein Z, median 72.5% (range: 3.4-123.7%) vs. 90.7% (range: 32.1-203.2%), P < 0.0001; ZPI antigen, 86.1% (range: 25.1-149.5%) vs. 93.2% (range: 48.9-171.3%), P = 0.004; ZPI function, 83.5% (range: 21.1-135.2%) vs. 97.2% (range: 50.5-175.5%), P < 0.0001]. The lowest tertiles of protein Z antigen [odds ratio (OR) 5.4, 95% confidence interval (CI) 2.2-13.5, P < 0.0001] and ZPI function (OR 2.4, 95% CI 1.1-5.5, P = 0.03) were associated with PAD on multivariate analysis after adjustment for age, gender, and traditional cardiovascular risk factors. A significant inverse relationship was also observed between protein Z and ZPI levels and the number of traditional cardiovascular risk factors and the clinical severity of disease (Fontaine stage).


CONCLUSIONS
Low levels of protein Z antigen and protein Z activity are significantly associated with the occurrence and severity of atherosclerotic PAD.
Sofi
F
F
Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Florence, Italy. francescosofi@gmail.com
Cesari
F
F
Tu
Y
Y
Pratesi
G
G
Pulli
R
R
Pratesi
C
C
Gensini
G F
GF
Abbate
R
R
Fedi
S
S
Broze
G J
GJ
D000368:Aged; D000369:Aged, 80 and over; D001798:Blood Proteins / Q000502:physiology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000503:physiopathology*; D015843:Serpins / Q000502:physiology*
D001798:Blood Proteins; C416370:SERPINA10 protein, human; D015843:Serpins; C026080:plasma protein Z