title: Autoantibodies isolated from preeclamptic patients induce endothelial dysfunction via interaction with the angiotensin II AT1 receptor.
abstract: Complete understanding of the etiology underlying endothelial damage in preeclampsia (PE) remains deficient. Recent studies suggest that autoantibodies against angiotensin II AT1 receptors (AT1-AA) may affect vascular endothelial integrity. However, direct evidence demonstrating association between AT1-AA from preeclamptic patients and vascular endothelial injury is lacking. The current study determined the effects of AT1-AA isolated from preeclamptic patients (Pre-IgG) upon the endothelium and attempted to elucidate the underlying mechanisms of injury. Pre-IgG markedly induced dose-dependent vasoconstriction in aortic vascular rings, an effect blocked by AT1 receptor antagonist losartan. Pre-IgG-induced vasoconstriction was increased in the absence of intact endothelium (1.59 ± 0.04 g vs. 1.63 ± 0.08 g, P < 0.05). Additionally, Pre-IgG incubation with human umbilical vein endothelial cells significantly increased lactate dehydrogenase release in a time-dependent manner (0.84 ± 0.07 vs. 3.50 ± 0.09, 24 vs. 72-h exposure group, P < 0.01) and increased caspase-3 and -8 activities (peaking at 48 h), but did not affect caspase-9 activity. Taken together, these results support the contribution of AT1-AA to endothelial cell injury and dysfunction in PE.
authors.affiliation: Department of Reproductive Center, Taiyuan Central Hospital, Taiyuan, 030001, Shanxi, People's Republic of China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Wayne Bond
authors.initials: WB
authors.lastname: Lau
authors.forename: Suli
authors.initials: S
authors.lastname: Zhang
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhang
authors.forename: Huirong
authors.initials: H
authors.lastname: Liu
authors.forename: Xin-Liang
authors.initials: XL
authors.lastname: Ma
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004789:Enzyme Activation; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D011225:Pre-Eclampsia / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: C544065:AGTR1 protein, human; D047228:Angiotensin II Type 1 Receptor Blockers; D001323:Autoantibodies; D044140:Receptor, Angiotensin, Type 1; D007770:L-Lactate Dehydrogenase; D020169:Caspases; D019808:Losartan