Autoantibody-mediated angiotensin receptor activation contributes to preeclampsia through tumor necrosis factor-alpha signaling.

ABSTRACT: Preeclampsia is a prevalent life-threatening hypertensive disorder of pregnancy for which the pathophysiology remains largely undefined. Recently, a circulating maternal autoantibody, the angiotensin II type I (AT(1)) receptor agonistic autoantibody (AA), has emerged as a contributor to disease features. Increased circulating maternal tumor necrosis factor alpha (TNF-alpha) is also associated with the disease; however, it is unknown whether this factor directly contributes to preeclamptic symptoms. Here we report that this autoantibody increases the proinflammatory cytokine TNF-alpha in the circulation of AT(1)-AA-injected pregnant mice but not in nonpregnant mice. Coinjection of AT(1)-AA with a TNF-alpha neutralizing antibody reduced cytokine availability in AT(1)-AA-injected pregnant mic

SUBMITTER: Irani RA 

PROVIDER: S-EPMC3380607 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature