P190	Circulating tissue kallikrein is upregulated in patients with acute myocardial infarction and correlates with functional, biochemical and cellular markers of adverse clinical outcome.
1W.Wojakowski, 1R.Wyderka, 1M.Tendera, 2A.Zebzda, 2M.Majka, 3M.Ratajczak, 4C.Emanueli, 4P.Madeddu
13rd Division of Cardiology, Silesian School of Medicine, 45-47 Ziołowa Street, 40-635, Katowice, PL; 2Department of Transplantology, Polish-American Children`s Hospital, Medical College, Jagiellonian University, 265 Wielicka Street, 30-663, Kraków, PL; 3Stem Cell Biology Program at James Graham Brown Cancer Center and Department of Medicine, University of Louisville, , KY 40202., Louisville, US; 4Experimental Cardiovascular Medicine, BHI, University of Bristol, Bristol, GB.

Adult bone marrow-derived stem cells are mobilized into peripheral blood in the setting of acute myocardial infarction (AMI), but this response is impaired in patients with low left ventricular ejection fraction (LVEF). Circulating levels of human tissue kallikrein (HTK), a pleiotropic angiogenic protein, are augmented according to the severity of atherosclerosis. The aim of the present study was twofold: (1) to validate the diagnostic value of HTK in AMI and (2) to ascertain if HTK correlates with established biomarkers of adverse clinical outcome. Twenty consecutive patients with ST-elevation AMI (STEMI) admitted < 12 hours after the chest pain onset were enrolled. Plasma samples were taken immediately after admission and 7 days after percutaneous coronary revascularization. Plasma levels of HTK, NT-proBNP, IL-10, VEGF-A, C-CSF, IL-18, and SDF-1 were measured by ELISA and CD34+ CXCR4+ stem cells by FACSCalibur flow-cytometer. In healthy subjects, HTK averaged 375±33 pg/mL, ranging from 160 to 658 pg/mL. In STEMI patients, mean baseline levels of HTK (1511±433 pg/mL, ranging from 416 to 7334 pg/mL) were significantly higher in comparison to healthy controls (P<0.01), but they then decreased at 7 days from revascularization (576±56pg/mL; ranging from 377 to 1262 pg/mL; P<0.005 vs. baseline). Median NT-proBNP level in STEMI patients was 296 ng/L (range 79-1573 ng/L). In patients with low LVEF (≤40%) the median NT-proBNP levels were significantly higher than in subjects with LVEF >40% (327 ng/L vs. 212 ng/L; P<0.03). The number of CD34+ CXCR4+ stem cells in peripheral blood was significantly higher in STEMI than in healthy subjects. In patients with low LVEF on admission, upper tertile of NT-proBNP and lower tertile of CXCR4+ CD34+ cells had higher HTK levels than those with good LVEF, low NT-proBNP and high number of cells at baseline (P<0.05). No significant correlations were found between absolute values or changes in relation to baseline levels of cytokines and HTK. In conclusion, circulating HTK is increased early in STEMI and reduced by revascularization. Importantly, the highest HTK levels were found in patients with low LVEF, high NT-proBNP and blunted mobilization of CXCR4/CD34+ stem cells on admission, which together are indicative of poor clinical outcome. Upregulation of angiogenic HTK may represent a compensatory response to AMI and help to predict the outcome of STEMI patients.

Copyright © 2005 S. Karger AG, Basel. Any further use of this abstract requires written permission from the publisher.