Circulating concentrations of fibroblast activation protein α in apparently healthy individuals and patients with acute coronary syndrome as assessed by sandwich ELISA.
BACKGROUND
Fibroblast activation protein α (FAP) is a membrane glycoprotein with dipeptidyl-peptidase and collagenase activity and is expressed in cancer, arthritis, and atherosclerotic plaques. We hypothesized that FAP can be measured quantitatively in the circulation and provide prognostic information in acute coronary syndrome (ACS).


METHODS
We assessed the performance of a commercially available FAP ELISA and the pre-analytic characteristics of the marker. We determined FAP concentrations in EDTA plasma samples from 101 apparently healthy blood donors and 407 patients with ACS. Patients were followed for 12 months regarding all-cause mortality and non-fatal myocardial infarction (MI).


RESULTS
FAP was stable at room temperature (for 1 day) and 4°C (3 days) and resistant to 3 freeze/thaw cycles. Recovery of recombinant human FAP ranged from 78 to 103% and serial dilutions of spiked samples resulted in measurements within 91 to 120% of expected values. Patients with ACS had lower plasma FAP concentrations compared with blood donors [median (25th-75th percentiles): 84 (69-101) ng/mL vs. 108 (87-124) ng/mL, P < 0.001]. Patients presenting with FAP concentrations in the first quartile had a 3.0-fold higher risk of death (95% confidence interval 1.4-6.2) compared with patients in the second to fourth quartiles (P = 0.004). FAP concentration was not related to the risk of MI.


CONCLUSIONS
Our study is the first to associate FAP with prognosis in ACS. The favorable pre-analytic characteristics of FAP will facilitate future studies of the marker in other disease settings associated with altered FAP expression.
Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany. Electronic address: tillmanns.jochen@mh-hannover.de.
Jochen
J
Tillmanns
Christian
C
Widera
Yasmin
Y
Habbaba
Paolo
P
Galuppo
Tibor
T
Kempf
Kai C
KC
Wollert
Johann
J
Bauersachs
D054058:Acute Coronary Syndrome / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001775:Blood Circulation / Q000502:physiology*; D010450:Endopeptidases; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D018093:Gelatinases / Q000097:blood*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000097:blood*; D055815:Young Adult; D000099167:Fibroblast Activation Protein Alpha
D015415:Biomarkers; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha
ACS; APCE; Acute coronary syndrome; Biomarker; C-reactive protein; CAD; CRP; DPP6; DPPIV; FAP; Fibroblast activation protein α; Inflammation; LV; MI; Mortality; N-terminal pro-B-type natriuretic peptide; NSTEMI; NT-proBNP; ST-elevation myocardial infarction; STEMI; acute coronary syndrome; antiplasmin-cleaving enzyme; cTnT; cardiac troponin T; coronary artery disease; dipeptidyl peptidase 6; dipeptidyl peptidase IV; eGFR; estimated glomerular filtration rate; high sensitivity; hs; left ventricular; myocardial infarction; non-ST-elevation myocardial infarction; recombinant human; rh