Angiotensin IV does not exert prothrombotic effects in vivo

Thrombosis and thromboembolism are serious clinical complications of cardiovascular diseases and are among the leading causes of mortality worldwide. Dysregulation of the renin-angiotensin system is associated with an increased incidence of thrombotic events. Angiotensin II (AngII) is known to enhance platelet aggregation, contributing to a prothrombotic state in patients. Important biological roles of other angiotensin peptides and their receptors have been shown, but their specific role in thrombus formation remains unclear. Recent evidence suggests a prothrombotic role of angiotensin IV (AngIV). To confirm the prothrombotic effects of AngIV and to further investigate AngIV-mediated mechanisms, we utilized osmotic minipumps to administer AngIV in mice continuously over 4 weeks. AngIV treatment did not induce thrombus formation in the heart, did not affect platelet numbers, and did not enhance platelet aggregation. HGF, c-MET, or PAI-1 expression levels in the heart were not affected by AngIV treatment in mice. Furthermore, we did not observe altered platelet aggregation of human platelets incubated with HGF. These findings indicate that AngIV does not regulate key prothrombotic mechanisms.