Tissue factor modulation by Angiotensin II: a clue to a better understanding of the cardiovascular effects of renin-angiotensin system blockade?
Systemic hypertension, a pathological process to which the renin-angiotensin system contributes importantly, is characterized by a thrombophilic diathesis and an increased risk for acute ischemic coronary events. That apparently contradictory profile might, to some extent, relate to the modulating properties of Angiotensin II, the effector arm of the renin angiotensin system, on tissue factor expression, the physiologic initiator of blood coagulation and a basic mechanism in the pathogenesis of acute thrombosis. In fact, monocytes and macrophages within the atherosclerotic plaque as well as inflamed vascular endothelial cells may locally synthesize Angiotensin II. In turn, the peptide, by binding to its specific membrane receptors, activates a series of intracellular signals eventually converging upon NF-kappaB, a transcription factor that upregulates tissue factor expression. Drugs interfering with the renin-angiotensin system, either by inhibiting conversion of Angiotensin I to Angiotensin II or by blocking its receptors, have the potential to inhibit tissue factor expression and to modulate its procoagulant effect. This property may contribute to the protection exerted by renin-angiotensin blockers from acute ischemic events in patients with hypertension and other cardiovascular diseases.
Celi
Alessandro
A
Dipartimento Cardio Toracico e Vascolare, Università di Pisa, Italy. r.pedrinelli@med.unipi.it
Del Fiorentino
Alessandra
A
Cianchetti
Silvana
S
Pedrinelli
Roberto
R
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology*; D013925:Thromboplastin / Q000096:biosynthesis / Q000502:physiology*
D016328:NF-kappa B; D000804:Angiotensin II; D013925:Thromboplastin