scholarly journals Fibrin‐specific pNIPAM Nanogels for Targeted Delivery of Tissue‐Type Plasminogen Activator to Treat Thrombotic Complications Are Well Tolerated In Vivo

2021 ◽  
Author(s):  
Emily P. Mihalko ◽  
Kimberly Nellenbach ◽  
Manasi Krishnakumar ◽  
Nina Moiseiwitsch ◽  
Jennifer Sollinger ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Targeted Delivery ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Thrombotic Complications

An Experimental Multiple-Organ Model for the Study of Regional Net Release/Uptake Rates of Tissue-type Plasminogen Activator in the Intact Pig

1997 ◽  
Vol 78 (03) ◽  
pp. 1150-1156 ◽  
Author(s):  
Christina Jern ◽  
Heléne Seeman-Lodding ◽  
Bjӧrn Biber ◽  
Ola Winsӧ ◽  
Sverker Jern
Keyword(s):  
Plasminogen Activator ◽  
Multiple Organ ◽  
Tissue Type ◽  
Hepatic Veins ◽  
Plasma Flows ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Uptake Rates ◽  
Net Release

SummaryExperimental data indicate large between-organs variations in rates of synthesis of tissue-type plasminogen activator (t-PA), which may reflect important differences in the capacity for constitutive and stimulated t-PA release from the vascular endothelium. In this report we describe a new multiple-organ experimental in vivo model for simultaneous determinations of net release/uptake rates of t-PA across the coronary, splanchnic, pulmonary, and hepatic vascular beds. In eleven intact anesthetized pigs, blood samples were obtained simultaneously from the proximal aorta, coronary sinus, pulmonary artery, and portal and hepatic veins. Plasma flows were monitored separately for each vascular region. Total plasma t-PA was determined by ELISA with a porcine t-PA standard. Regional net release/uptake rates were defined as the product of arteriovenous concentration gradients and local plasma flows. The net release of t-PA across the splanchnic vascular bed was very high, with a mean output of 1,919 ng total t-PA X min-1 (corresponding to 90 ng per min and 100 g tissue). The net coronary t-PA release was 68 ng X min-1 (30 ng X min-1 X 100 g"1)- Pulmonary net fluxes of t-PA were variable without any significant net t-PA release. The net hepatic uptake rate was 4,855 ng X min-1 (436 ng X min-1 X 100 g-1). Net trans-organ changes of active t-PA mirrored those of total t-PA. The results demonstrate marked regional differences in net release rates of t-PA in vivo. The experimental model we present offers new possibilities for evaluation of regional secretion patterns in the intact animal.

Behaviour and Quantitation of Extrinsic (Tissue-Type) Plasminogen Activator in Human Blood

1983 ◽  
Vol 50 (02) ◽  
pp. 518-523 ◽  
Author(s):  
C Kluft ◽  
A F H Jie ◽  
R A Allen
Keyword(s):  
Plasminogen Activator ◽  
Venous Occlusion ◽  
Tissue Type ◽  
Functional Assay ◽  
Uterine Tissue ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Baseline Values

SummaryFunctional assay of extrinsic (tissue-type) plasminogen activator (EPA) in plasma on fibrin plates was evaluated. Using specific quenching antibodies, we demonstrated the method to be specific for EPA under all conditions tested. Contributions of urokinases and intrinsic activators were excluded. The quantity of EPA in blood samples, as compared with purified uterine tissue activator, shows 1 blood activator unit (BAU) to be comparable to 0.93 ng.The median values for EPA activity for healthy volunteers were: baseline, 1.9 BAU/ml (n = 123); diurnal, 5.5 BAU/ml (n = 12); DDAVP administration, 11.7 BAU/ml (n = 39); exhaustive exercise, 25 BAU/ml (n = 24); venous occlusion (15 min), 35 BAU/ml (n = 61). A large inter-individual variation in EPA activity was found, while individual baseline values tended to be constant for periods of weeks.In vitro in blood EPA activity shows a disappearance of 50% in about 90 min at 37° C; EPA activity in euglobulin fractions is stable for ≤2 hr at 37° C.A rapid decrease in EPA activity occurs in vivo, as noted after extracorporal circulation and exercise stimulation (t½ decay, 2-5 min).

LEUKOTRIENES INDUCE THE ACUTE RELEASE OF TISSUE-TYPE PLASMINOGEN ACTIVATOR FROM PERFUSED RAT BLOOD VESSEL WALLS

1987 ◽  
Author(s):  
N Tranquille ◽  
J J Emeis
Keyword(s):  
Blood Vessel ◽  
Plasminogen Activator ◽  
Prostaglandin E1 ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Acute Increase ◽  
Vessel Walls ◽  
Isolated Rat

In a previous publication (Blood 66, 86, 1985) we suggested, on the basis of inhibitor experiments, that lipoxygenase metabolites might be involved in the release of tissue-type plasminogen activator (t-PA) from vessel walls. To test this suggestion, isolated rat hindlegs were freed of blood with Tyrode-BSA solution, and subsequently perfused with Tyrode-BSA containing various lipoxygenase metabolites. The perfusate was collected at timed intervals and assayed for t-PA activity by a spectrophoto-metric procedure. Of the compounds tested (see Table) 5-HETE did not induce PA release. However, leukotriene (LT) C4 and LTD4 dose-dependently (10-200 nM) induced the release of t-PA, which plateaued at 160 and 200 nM, respectively. Peak levels of t-PA activity were found at one minute, although the amount of t-PA released was less than that induced by PAF-acether. The PA activity released proved to be t-PA by functional and immunological criteria. Release of t-PA induced by LTC4 and LTD 4 was inhibited by the LT receptor antagonist FPL-55712 (10 μM).Prostaglandin E1 and E2, prostacyclin and ZK 36374 did not induce acute t-PA release at 0.1-2.8 μM concentrations in our model. LTC4 and LTD4 also induced an acute increase of t-PA activity in vivo in rats at a dosage of 2 μg/kg i.v.The data show that LTC4 and LTD4 can directly induce the acute release of t-PA, possibly by interacting with an endothelial LT receptor.

scholarly journals PAF-acether-induced release of tissue-type plasminogen activator from vessel walls

Blood ◽  
1985 ◽  
Vol 66 (1) ◽  
pp. 86-91 ◽  
Author(s):  
JJ Emeis ◽  
C Kluft
Keyword(s):  
Plasminogen Activator ◽  
Vascular Endothelial Cells ◽  
Platelet Activating Factor ◽  
Cyclooxygenase Inhibitors ◽  
Tissue Type ◽  
Lipoxygenase Pathway ◽  
Lipoxygenase Inhibitors ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

Abstract Platelet-activating factor (PAF-acether; 1–0-octadecyl-2-acetyl-sn- glyceryl-3-phosphorylcholine) induced the release of plasminogen activator in rat, both in vivo and in perfused hind legs. The released plasminogen activator was shown by immunologic and functional criteria to be tissue-type plasminogen activator (t-PA). Release of t-PA by PAF- acether could be inhibited by phospholipase inhibitors and by lipoxygenase inhibitors, but not by cyclooxygenase inhibitors. It is suggested that PAF-acether induces the release of t-PA from vascular endothelial cells by the (calcium-dependent) activation of a phospholipase-lipoxygenase pathway.

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