Thromboxane mediates neutrophil superoxide production in pregnancy

Vaughan, John E.; Walsh, Scott W.; Ford, George D.

doi:10.1016/j.ajog.2006.02.053

Cited by 23 publications

(25 citation statements)

References 22 publications

(6 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, meta-analysis of low-dose aspirin trials demonstrates aspirin is effective in preventing preeclampsia 43, 44 , the effectiveness of which is related to patient compliance 45 . The ability of aspirin to reduce preeclampsia may be due to its ability to inhibit neutrophil superoxide production 46 , which would be consistent with the findings of our study.…”

Section: Perspectivessupporting

confidence: 92%

Mechanisms of Enhanced Vascular Reactivity in Preeclampsia

et al. 2011

Self Cite

View full text Add to dashboard Cite

Preeclamptic women have enhanced blood pressure response to angiotensin II and extensive systemic vascular infiltration of neutrophils. Neutrophils release reactive oxygen species that might activate the RhoA kinase pathway to enhance vascular reactivity. We hypothesized that enhanced vascular reactivity in preeclampsia is due to neutrophil mediated reactive oxygen species activation of the RhoA kinase pathway. Omental arteries were obtained at cesarean section and studied using a myograph system. We found that arteries of preeclamptic women had extensive infiltration of neutrophils and enhanced reactivity to angiotensin II. Treatment of arteries of normal pregnant women with reactive oxygen species or activated neutrophils enhanced vessel reactivity to angiotensin II mimicking preeclamptic vessels. Pretreatment with superoxide dismutase/catalase to quench reactive oxygen species, or RhoA kinase inhibitor blocked enhanced responses in preeclamptic and normal vessels. Reactive oxygen species also enhanced vessel reactivity to norepinephrine, which was blocked by RhoA kinase inhibition. Treatment of arteries with reactive oxygen species increased RhoA kinase activity 3-fold, whereas culture of human vascular smooth muscle cells with angiotensin II and activated neutrophils or reactive oxygen species resulted in phosphorylation of key proteins in the RhoA kinase pathway. We conclude that enhanced vascular reactivity of omental arteries in preeclampsia is due to reactive oxygen species activation of the RhoA kinase pathway, and that enhanced vascular reactivity is likely due to the infiltration of neutrophils. We speculate that neutrophil infiltration into systemic vasculature of preeclamptic women is an important mechanism for hypertension.

show abstract

Section: Perspectivessupporting

confidence: 92%

Mechanisms of Enhanced Vascular Reactivity in Preeclampsia

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…26,48 Evidence presented in this study suggests that the potential mechanism for MMP-1 induction and activation may involve the generation of ROS and TNF-␣ by infiltrated neutrophils. This notion is supported by studies 13,15,16,49 showing that TNF-␣ and ROS modulate the expression of different MMPs in VSMCs and promote the activation of MMPs secreted by VSMCs.…”

Section: Discussionmentioning

confidence: 77%

“…25 Arachidonic acid was used to activate the neutrophils because it is elevated in preeclamptic women and stimulates superoxide production by neutrophils. 26 Activated neutrophils were washed before exposure to VSMCs. Conditioned medium was collected and centrifuged for removal of cell debris.…”

Section: Vsmc Culture and Treatmentmentioning

confidence: 99%

Increased Expression of Matrix Metalloproteinase-1 in Systemic Vessels of Preeclamptic Women

Estrada-Gutiérrez

Cappello

Mishra

et al. 2011

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

This study was conducted to determine the following: (1) whether matrix metalloproteinase-1 (MMP-1) is increased in systemic vessels of preeclamptic women, (2) whether this increase might be mediated by neutrophils, and (3) whether MMP-1 could be responsible for vascular dysfunction. Omental arteries and plasma were collected from healthy pregnant and preeclamptic women. Omental arteries were evaluated for gene and protein expression of MMP-1, collagen type 1␣, tissue inhibitor of metalloproteinase-1, and vascular reactivity to MMP-1. Gene and protein expression levels were also evaluated in human vascular smooth muscle cells (VSMCs) co-cultured with activated neutrophils, reactive oxygen species, or tumor necrosis factor ␣. Vessel expression of MMP-1 and circulating MMP-1 levels were increased in preeclamptic women, whereas vascular expression of collagen or tissue inhibitor of metalloproteinase-1 were down-regulated or unchanged. In cultured VSMCs, the imbalance in collagen-regulating genes of preeclamptic vessels was reproduced by treatment with neutrophils, tumor necrosis factor ␣, or reactive oxygen species. Chemotaxis studies with cultured cells revealed that MMP-1 promoted recruitment of neutrophils via vascular smooth muscle release of interleukin-8. Furthermore, MMP-1 induced vasoconstriction via protease-activated receptor-1, whose expression was significantly increased in omental arteries of preeclamptic women and in VSMCs co-cultured with neutrophils. Collectively, these findings disclose a novel role for MMP-1 as a mediator of vasoconstriction and vascular dysfunction in preeclampsia.

show abstract

“…Oxidized lipids are potent activators of neutrophils and cause their expression of COX-2 which regulates their release of thromboxane, TNFα and superoxide (25,26). Neutrophils obtained from preeclamptic women express significantly more COX-2 than neutrophils obtained from normal pregnant women or normal nonpregnant women (27).…”

Section: Discussionmentioning

confidence: 99%

Neutrophils, but Not Lymphocytes or Monocytes, Infiltrate Maternal Systemic Vasculature in Women with Preeclampsia

Cadden

Walsh

2008

Hypertension in Pregnancy

Self Cite

View full text Add to dashboard Cite

Objective-Leukocytes are activated in women with preeclampsia, but the class of leukocytes that infiltrates the maternal vasculature and, therefore, most likely to cause vascular dysfunction is not known.Methods-Subcutaneous fat biopsies were obtained at cesarean section or abdominal surgery from 7 normal nonpregnant women, 7 normal pregnant women, and 7 preeclamptic women. Tissues were immunohistochemically stained for CD14, a monocyte/macrophage antigen, CD99, a lymphocyte antigen, and CD66b, a neutrophil antigen.Results-CD14 stained cells were found infiltrated into fat tissue but were not present in vessels for any of the groups. CD99 stained cells were present in approximately 20-30% of vessels with no difference among groups. CD66b stained cells were present in all groups with a significantly greater percentage of vessels stained for preeclamptic than normal pregnant or normal nonpregnant women (70±6 vs. 43±9 vs. 21±5%, respectively, P<0.01). CD66b cells were the most abundant cell type that infiltrated vessels of preeclamptic women. Conclusions-1)There was significantly more neutrophils adhered to endothelium and infiltrated into the intimal space in the maternal systemic vasculature of preeclamptic women than in normal pregnant women or normal nonpregnant women; 2) There was no significant difference in lymphocyte infiltration among the patient groups and lymphocytes were present in much lower numbers than neutrophils; 3) Monocytes/macrophages were found in fat tissue but not in vessels. We speculate that neutrophils are the class of leukocytes that cause the majority of vascular cell dysfunction in preeclamptic women.

show abstract

Thromboxane mediates neutrophil superoxide production in pregnancy

Cited by 23 publications

References 22 publications

Mechanisms of Enhanced Vascular Reactivity in Preeclampsia

Mechanisms of Enhanced Vascular Reactivity in Preeclampsia

Increased Expression of Matrix Metalloproteinase-1 in Systemic Vessels of Preeclamptic Women

Neutrophils, but Not Lymphocytes or Monocytes, Infiltrate Maternal Systemic Vasculature in Women with Preeclampsia

Contact Info

Product

Resources

About