An increase in aldosterone levels positively correlates with an increased risk of acute cardiovascular thrombotic events. The aim of the study was to determine the mechanism of action of prothrombotic aldosterone focusing on the rapid effects of the hormone on platelets, coagulation, and fibrinolysis. A wide panel of advanced ex vivo and in vitro techniques was used for the evaluation of coagulation and fibrinolysis in aldosterone-treated rats. Additionally, two experimental mice models of thrombosis, which allowed for the intravital observation of the first stage of thrombus formation in real time, were used. Acute administration of aldosterone in rats increased the density of fibrin net and platelet aggregates in clots as well as reduced fibrinolysis. These effects were observed within 10 min and were partially suppressed by eplerenone. Moreover, acute administration of aldosterone in mice enhanced platelet accumulation at the site of endothelial injury induced by laser and increased the area of irreversibly activated platelets in FeCl3-induced thrombus. These results demonstrate that aldosterone acutely affects platelets, coagulation, and fibrinolysis, leading to an enhanced thrombosis. The aldosterone effects were mediated partially via a mineralocorticoid receptor. The mechanism seems to involve non-genomic signaling since the effects were observed within a few minutes of aldosterone administration.
Authors: Anna Gromotowicz-Poplawska, Natalia Marcinczyk, Tomasz Misztal, Agata Golaszewska, Michal Aleksiejczuk, Tomasz Rusak, Ewa Chabielska
Keywords: aldosterone, coagulation, fibrinolysis, platelet, thrombosis
DOI Number: 10.1016/j.vph.2019.106598 Publication Year: 2019
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