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Thromb Haemost 2013; 110(06): 1121-1134
DOI: 10.1160/TH13-05-0381
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

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

Judit Cubedo
1   Barcelona Cardiovascular Research Center (CSIC-ICCC), Barcelona, Spain
2   Biomedical Research Institute Sant Pau (IBB-Sant Pau), Barcelona, Spain
,
Ilaria Ramaiola
1   Barcelona Cardiovascular Research Center (CSIC-ICCC), Barcelona, Spain
2   Biomedical Research Institute Sant Pau (IBB-Sant Pau), Barcelona, Spain
,
Teresa Padró
1   Barcelona Cardiovascular Research Center (CSIC-ICCC), Barcelona, Spain
2   Biomedical Research Institute Sant Pau (IBB-Sant Pau), Barcelona, Spain
,
Victoria Martin-Yuste
4   Cardiology Department Hospital Clinic, Barcelona, Spain
,
Manel Sabate-Tenas
4   Cardiology Department Hospital Clinic, Barcelona, Spain
,
Lina Badimon
1   Barcelona Cardiovascular Research Center (CSIC-ICCC), Barcelona, Spain
2   Biomedical Research Institute Sant Pau (IBB-Sant Pau), Barcelona, Spain
3   Autonomous University of Barcelona, Barcelona, Spain
› Author Affiliations Financial support: This work was supported by SAF 2010–16549 to L.B., FIS PI10–01115 to T.P., and TERCEL RD06/010017 to L.B. from Instituto Carlos III. J.C. was recipient of a grant from „Fundación de Investigación Cardiovascular-Fundación Jesus Serra” in 2011. I.R. is recipient of a predoctoral grant from the ICCC (2008–2013).
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Publication History

Received: 09 May 2013

Accepted after major revision: 23 July 2013

Publication Date:
30 November 2017 (online)

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Summary

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.

Keywords

Acute myocardial infarction - high-molecular weight kininogen - fibrinogen - thrombus - proteomics

 

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