Shirley Uitte de Willige1, Joyce J M C Malfliet2, Jaap W Deckers3, Diederik W J Dippel4, Frank W G Leebeek2, Dingeman C Rijken2. 1. Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: s.uittedewillige@erasmusmc.nl. 2. Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands. 3. Department of Cardiology, Erasmus University Medical Center, Rotterdam, The Netherlands. 4. Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Abstract
BACKGROUND: Fibroblast activation protein (FAP) is a transmembrane glycoprotein with dipeptidyl-peptidase and endopeptidase activities and circulates in blood in a truncated, soluble form (sFAP). Fibrinolysis inhibitor α2-antiplasmin (α2AP) has been described as a potential in vivo substrate of sFAP. We aimed to investigate sFAP levels and α2AP cleavage in young arterial thrombosis patients and in control individuals, study the correlation between sFAP levels and α2AP cleavage and investigate determinants of these variables. METHODS: sFAP levels and α2AP cleavage were determined by ELISA in the plasma samples of 391 coronary heart disease (CHD) patients, 221 ischemic stroke patients, 51 peripheral arterial disease patients and 501 control individuals. RESULTS: Median sFAP levels were similar in arterial thrombotic patients and in control individuals, but in CHD patients sFAP levels significantly increased with time (number of months) between the event and study inclusion (Spearman's rho: 0.209, p<0.001), indicating reduced sFAP levels at time of event. sFAP levels and percentage α2AP cleavage significantly correlated in controls and in patients. Furthermore, sex, use of oral contraceptives and hyperlipidemia were significant determinants of sFAP levels. CONCLUSIONS: sFAP levels were reduced in the CHD patient population, but only in the first months after the event, indicating that over time sFAP levels may normalize. The significant correlation between sFAP level and α2AP cleavage indicates that in vivo sFAP (at least partly) regulates cleavage of α2AP, irrespective of disease status. Differences in sFAP level due to sex, use of oral contraceptives and hyperlipidemia might suggest hormonal control of sFAP levels.
BACKGROUND:Fibroblast activation protein (FAP) is a transmembrane glycoprotein with dipeptidyl-peptidase and endopeptidase activities and circulates in blood in a truncated, soluble form (sFAP). Fibrinolysis inhibitor α2-antiplasmin (α2AP) has been described as a potential in vivo substrate of sFAP. We aimed to investigate sFAP levels and α2AP cleavage in young arterial thrombosispatients and in control individuals, study the correlation between sFAP levels and α2AP cleavage and investigate determinants of these variables. METHODS:sFAP levels and α2AP cleavage were determined by ELISA in the plasma samples of 391 coronary heart disease (CHD) patients, 221 ischemic strokepatients, 51 peripheral arterial diseasepatients and 501 control individuals. RESULTS: Median sFAP levels were similar in arterial thromboticpatients and in control individuals, but in CHD patientssFAP levels significantly increased with time (number of months) between the event and study inclusion (Spearman's rho: 0.209, p<0.001), indicating reduced sFAP levels at time of event. sFAP levels and percentage α2AP cleavage significantly correlated in controls and in patients. Furthermore, sex, use of oral contraceptives and hyperlipidemia were significant determinants of sFAP levels. CONCLUSIONS:sFAP levels were reduced in the CHD patient population, but only in the first months after the event, indicating that over time sFAP levels may normalize. The significant correlation between sFAP level and α2AP cleavage indicates that in vivo sFAP (at least partly) regulates cleavage of α2AP, irrespective of disease status. Differences in sFAP level due to sex, use of oral contraceptives and hyperlipidemia might suggest hormonal control of sFAP levels.
Authors: Premarani Sinnathurai; Wendy Lau; Ana Julia Vieira de Ribeiro; William W Bachovchin; Helen Englert; Graydon Howe; David Spencer; Nicholas Manolios; Mark D Gorrell Journal: Int J Rheum Dis Date: 2016-12-19 Impact factor: 2.454
Authors: Shirley Uitte de Willige; Fiona M Keane; David G Bowen; Joyce J M C Malfliet; H Emma Zhang; Bharvi Maneck; Geoffrey W McCaughan; Frank W G Leebeek; Dingeman C Rijken; Mark D Gorrell Journal: PLoS One Date: 2017-06-05 Impact factor: 3.240
Authors: Zsuzsa Bagoly; Barbara Baráth; Rita Orbán-Kálmándi; István Szegedi; Réka Bogáti; Ferenc Sarkady; László Csiba; Éva Katona Journal: Biomolecules Date: 2021-02-25