Summary
To investigate the role of active plasminogen activator inhibitor 1 (PAI-1) in the
evolution of a microthrombus generated in the arteriolar microcirculation, the monoclonal
antibody, 33H1F7, which transforms active PAI-1 to a tissue type plasminogen activator
(t-PA) substrate, was evaluated in an arteriolar thrombosis model in the rat mesentery.
Arterioles (200-300 μm) were stimulated electrically to create an endothelial lesion;
ADP was then perfused for 2 min to induce the formation of a platelet-rich thrombus
which lysed spontaneously in 140 ± 24 s. Two successive ADP superfusions produced
comparable thrombi which lysed in comparable times. Different doses of 33H1F7 were
infused to rats for 30 min and the dose which inactivates rapidly and totally active
rat PAI-1 (300 μg/kg/min) was selected to be tested on the thrombosis model. Infusion
of 33H1F7 beginning 10 min before the ADP application significantly reduced the lysis
time in comparison to the control (123 ± 30 s versus 169 ± 33 s, P < 0.05, paired
Student’s t-test) and the cumulative thrombus area during the lysis period was decreased
by 56 ± 7%. These results demonstrate that inactivation of PAI-1 is able to accelerate
lysis of a platelet-rich clot in a mesenteric arteriole of the rat. Thus active PAI-1
most likely participates to the resistance to thrombolysis in the arteriolar microcirculation
and its inactivation may shorten ischemic periods after microvascular obstruction
such as e.g. during cerebral stroke.
Keywords
PAI-1 - thrombolysis - experimental model - microcirculation - rat
