Angiotensin II, tissue factor and the thrombotic paradox of hypertension

Abstract

Tissue factor (TF), the physiologic initiator of blood coagulation, may contribute to the increased risk of thrombotic complications that characterizes arterial hypertension, as suggested by hypertensive animal models showing evidence for TF activation, and clinical studies in hypertensive patients at higher cardiovascular risk with increased circulating levels of TF and thrombogenic microparticles. Angiotensin II stimulates TF expression both in vitro and in vivo, an effect abolished by ACE or angiotensin II receptor inhibition. Moreover, renin–angiotensin system blockers, including aliskiren, a direct renin inhibitor, are able to modulate TF expression in monocytes and vascular endothelial cells activated by inflammatory cytokines. This behavior is suggestive of anti-inflammatory and anti-thrombotic properties of renin–angiotensin system blockers, and is compatible with the possibility that blocking local renin–angiotensin system activation might downregulate TF, thus reducing the risk of ischemic complications in hypertensive patients.

Keywords::

• ACE inhibitors
• aliskiren
• angiotensin II receptor blockers
• coagulation
• hypertension
• P-selectin
• renin–angiotensin system
• tissue factor

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.