Radiolabeled r-hirudin as a measure of thrombin activity at or within the rabbit aorta wall in vitro and in vivo
Research article published in Thrombosis and haemostasis (1994)
Abstract
The behavior of 125I-labeled recombinant hirudin towards the uninjured and de-endothelialized rabbit aorta wall has been studied in vitro and in vivo to determine its usefulness as an indicator of thrombin activity associated with the aorta wall. Thrombin adsorbed to either sulfopropyl-Sephadex or heparin-Sepharose bound > 95% of 125I-r-hirudin and the complex remained bound to the matrix. Binding of 125I-r-hirudin to the exposed aorta subendothelium (intima-media) in vitro was increased substantially if the tissue was pre-treated with thrombin; the quantity of 125I-r-hirudin bound to the de-endothelialized intima-media (i.e. balloon-injured in vitro) correlated positively with the quantity of bound 131I-thrombin (p < 0.01). Aortas balloon-injured in vivo were measured for thrombin release from, and binding of 125I-r-hirudin to, the de-endothelialized intimal surface in vitro; 125I-r-hirudin binding correlated with the amount of active thrombin released (p < 0.001). Uptake of 125I-r-hirudin by the aorta wall in vivo was proportional to the uptake of 131I-fibrinogen (as an indicator of thrombin activity) before and after balloon injury. After 30 min in the circulation, specific 125I-r-hirudin binding to the uninjured and de-endothelialized (at 1.5 h after injury) aorta wall was equivalent to 3.4 (+/- 2.5) and 25.6 (+/- 18.1) fmol of thrombin/cm2 of intima-media, respectively. Possibly, only hirudin-accessible, glycosaminoglycan-bound thrombin is measured in this way.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Zusammenfassung
Radiolabeled r-hirudin as a measure of thrombin activity at or within the rabbit aorta wall in vitro and in vivo.
Warum dies für die Hirudotherapie relevant ist
This study examined 125I-labeled recombinant hirudin as an indicator of thrombin activity associated with the rabbit aorta wall, both in vitro and in vivo. In thrombin-pretreated and balloon-injured de-endothelialized tissue, 125I-r-hirudin binding correlated positively with bound thrombin (p < 0.01 in vitro) and with active thrombin released (p < 0.001 in vivo); in vivo uptake also paralleled 131I-fibrinogen uptake. After 30 minutes in the circulation, specific binding corresponded to approximately 3.4 fmol thrombin/cm² in uninjured and 25.6 fmol/cm² in de-endothelialized aorta. For ASH's domain, the relevance is indirect: hirudin is the thrombin inhibitor originally characterized from the medicinal leech, and the study exploits its high binding specificity for thrombin on vascular surfaces. However, this is an animal (rabbit) study using recombinant hirudin as a research probe, not a therapeutic hirudotherapy investigation, and the authors note it may detect only glycosaminoglycan-bound, hirudin-accessible thrombin.
Zitation
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