High-molecular-weight kininogen and the intrinsic coagulation pathway in patients with de novo acute myocardial infarction

Abstract

After an acute ischaemic event serum proteins may change reflecting the ischaemic damage. Proteomic studies could provide new insights into potential biomarkers in the evolution of ischaemic syndromes. In this study we have investigated the coordinated changes in coagulation-related proteins in the evolution after an acute myocardial infarction (AMI). Serum proteome (2D-electrophoresis and MALDI-TOF/TOF) of AMI-patients within the first 6 hours after event onset (admission-time) and 3 days after were compared to controls. Systems biology and bioinformatic analysis were performed to identify the differentially expressed canonical pathways. In silico analysis of differential proteins revealed changes in the intrinsic coagulation pathway in the early phase post-AMI. The two identified high-molecular weight kininogen (HMWK) clusters were inversely correlated in AMI patients at admission, being the intensity of the low-molecular-weight form inversely related to myocardial necrosis (p<0.05). Factor XI (FXI) levels were decreased in AMI patients at admission and normalised 3 days after (p<0.05). There was an early increase in fibrinogen gamma and D-dimer at admission, followed by a decrease in fibrinogen turnover 3 days after (p<0.05). The influence of elapsed time of ischaemia on fibrinogen distribution changes was validated in coronary thrombi retrieved by thromboaspiration. In conclusion, our results demonstrate an active exchange between HMWK forms and a decrease in FXI indicative of intrinsic pathway activation, together with an increase in fibrinogen gamma turnover and D-dimer formation in the early phase post-AMI. Moreover, coronary thrombi showed a dynamic evolution in fibrinogen composition depending on the duration of ischaemia influencing serum fibrinogen-related products content.

Urine proteome analysis as a discovery tool in patients with deep vein thrombosis and pulmonary embolism

“…Urinary fragments of fibrinogen α were also identified in patients with CAD a disease that is associated with the development of plaque rupture‐induced microthrombi. Similarly, an increase of fibrinogen in plasma was observed in patients after acute myocard infarction . Specifically, the fibrinogen α fragment 607–622 was up‐regulated in CAD, as it was the case in this study; a finding which could indicate specific peptidase activity, as seen in blood of patients with cancer .…”

Overlap of proteomics biomarkers between women with pre-eclampsia and PCOS: a systematic review and biomarker database integration

“…Moreover, they are a mediator of inflammation and cause increases in vascular permeability, stimulation of nociceptors, and release of other mediators of inflammation ( Wong and Takei, 2013 ). These mechanisms have been implicated in the pathogenesis of both PE and PCOS ( Gugliucci and Ghitescu, 2002 ; Tousoulis et al , 2008 ; Szarka et al , 2010 ; Redman, 2011 ; Yun et al , 2012 ; Cubedo et al , 2013 ).…”

“…Peroxiredoxin 2 was found to be down-regulated in both PE and PCOS in placental and omental biopsy, respectively ( Gatter et al , 1983 ). In view of the essential role of peroxiredoxin in protecting cells against H 2 O 2 -induced cell damage and apoptosis, down-regulation in placentae of women with PE emphasizes the role of oxidative stress as an important factor in the development of PE ( Cubedo et al , 2013 ). Furthermore, recent studies have advocated that oxidative stress stimulates androgen-producing steroidogenic enzymes leading to the hyperandrogenism observed in women with PCOS ( Burton and Jauniaux, 2004 ).…”

Molecular signature of coronary stent thrombosis: oxidative stress and innate immunity cells

“…For proteomic studies, protein extraction was performed using urea/detergent buffer (7 mol/L urea; 2mol/L thiourea; 2% CHAPS) as previously described (2,3). Protein concentration was measured with 2D-Quant Kit (GE Healthcare, Uppsala, Sweden).…”