Role of B1 and B2 lymphocytes in placental ischemia-induced hypertension.

Preeclampsia is a prevalent pregnancy complication characterized by new-onset maternal hypertension and inflammation, with placental ischemia as the initiating event. Studies of others have provided evidence for the importance of lymphocytes in placental ischemia-induced hypertension; however, the contributions of B1 versus B2 lymphocytes are unknown. We hypothesized that peritoneal B1 lymphocytes are important for placental ischemia-induced hypertension.

Interactions between the complement and endothelin systems in normal pregnancy and following placental ischemia.

Preeclampsia is characterized by new onset hypertension and fetal growth restriction and is associated with aberrant activation of the innate immune complement system and stressed or ischemic placenta. Previous studies have suggested a role for both endothelin and complement system activation products in new onset hypertension in pregnancy, but inter-relationships of the pathways are unclear. We hypothesized that complement activation following placental ischemia stimulates the endothelin pathway to cause hypertension and impair fetal growth.

Effect of nicotine on placental ischemia-induced complement activation and hypertension in the rat.

Preeclampsia is a pregnancy-specific condition manifested by new-onset maternal hypertension with systemic inflammation, including increased innate immune system complement activation. While exact pathophysiology is unknown, evidence suggests that inadequate spiral artery invasion and resulting utero-placental insufficiency is the initiating event. Cigarette smoking during pregnancy decreases the risk of preeclampsia.

From apelin to exercise: emerging therapies for management of hypertension in pregnancy.

Studies over the last couple of decades have provided exciting new insights into mechanisms underlying the pathogenesis of preeclampsia. In addition, several novel and innovative molecules and ideas for management of the syndrome have also come forth. While our basic understanding of the initiating events of preeclampsia continues to be placental ischemia/hypoxia stimulating the release of a variety of factors from the placenta that act on the cardiovascular and renal systems, the number of candidate pathways for intervention continues to increase.

Role of IgM and angiotensin II Type I receptor autoantibodies in local complement activation in placental ischemia-induced hypertension in the rat.

Preeclampsia is characterized by development of hypertension during pregnancy and reduced placental perfusion. Previous studies in a rat model of placental ischemia-induced hypertension demonstrated that inhibiting complement activation attenuated increased maternal blood pressure with C3a and C5a identified as the important products of complement activation. Given that in other forms of ischemia both natural IgM and antigen antibody complexes initiate complement activation, we hypothesized that placental ischemia exposes neoepitopes recognized by IgM to cause local complement activation and hypertension.

Neutrophil Depletion Attenuates Placental Ischemia-Induced Hypertension in the Rat.

Preeclampsia is characterized by reduced placental perfusion with placental ischemia and hypertension during pregnancy. Preeclamptic women also exhibit a heightened inflammatory state and greater number of neutrophils in the vasculature compared to normal pregnancy. Since neutrophils are associated with tissue injury and inflammation, we hypothesized that neutrophils are critical to placental ischemia-induced hypertension and fetal demise.

The complement system and adverse pregnancy outcomes.

Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the fetal allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival.

Differential effects of complement activation products c3a and c5a on cardiovascular function in hypertensive pregnant rats.

Early-onset pre-eclampsia is characterized by decreased placental perfusion, new-onset hypertension, angiogenic imbalance, and endothelial dysfunction associated with excessive activation of the innate immune complement system. Although our previous studies demonstrated that inhibition of complement activation attenuates placental ischemia-induced hypertension using the rat reduced uterine perfusion pressure (RUPP) model, the important product(s) of complement activation has yet to be identified. We hypothesized that antagonism of receptors for complement activation products C3a and C5a would improve vascular function and attenuate RUPP hypertension.

Endoplasmic Reticulum Stress Activation during Total Knee Arthroplasty.

Total knee arthroplasty (TKA) is the most common remediation for knee pain from osteoarthritis (OA) and is performed 650,000 annually in the U.S. A tourniquet is commonly used during TKA which causes ischemia and reperfusion (I/R) to the lower limb but the effects of I/R on muscle are not fully understood.

Complement activation is critical for placental ischemia-induced hypertension in the rat.

Preeclampsia is a major obstetric problem defined by new-onset hypertension and proteinuria associated with compromised placental perfusion. Although activation of the complement system is increased in preeclampsia compared to normal pregnancy, it remains unclear whether excess complement activation is a cause or consequence of placental ischemia. Therefore, we hypothesized that complement activation is critical for placental ischemia-induced hypertension.

Pravastatin attenuates hypertension, oxidative stress, and angiogenic imbalance in rat model of placental ischemia-induced hypertension.

Preeclampsia is a pregnancy-specific condition characterized by an imbalance of circulating angiogenic factors and new-onset hypertension. Although current treatment options are limited, recent studies suggest that pravastatin may improve angiogenic profile and reduce blood pressure in preeclampsia. We hypothesized pravastatin would restore angiogenic balance and reduce mean arterial pressure (MAP) in rats with reduced utero-placental perfusion pressure (RUPP)-induced hypertension.

AICAR administration ameliorates hypertension and angiogenic imbalance in a model of preeclampsia in the rat.

Previous studies suggest restoration of angiogenic balance can lower blood pressure and improve vascular endothelium function in models of preeclampsia. Our laboratory has recently reported exercise training mitigates hypertension in an animal model of preeclampsia, but the mechanisms are unknown. AMP-activated protein kinase (AMPK) is stimulated during exercise and has been shown to increase expression of VEGF.

Exercise training attenuates placental ischemia-induced hypertension and angiogenic imbalance in the rat.

An imbalance between proangiogenic (vascular endothelial growth factor) and antiangiogenic (soluble fms-like tyrosine kinase 1) factors plays an important role in hypertension associated with reduced uteroplacental perfusion (RUPP). Exercise has been shown to stimulate proangiogenic factors, such as vascular endothelial growth factor, in both the pregnant and nonpregnant state; thus, we hypothesized that exercise training would attenuate both angiogenic imbalance and hypertension attributed to RUPP. Four groups of animals were studied, RUPP and normal pregnant controls and normal pregnant and RUPP+exercise training.

Timing of ischemic insult alters fetal growth trajectory, maternal angiogenic balance, and markers of renal oxidative stress in the pregnant rat.

Increased uterine artery resistance and angiogenic imbalance characterized by increased soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased free vascular endothelial growth factor (VEGF) are often associated with placental insufficiency and preeclampsia but not synonymous with hypertension. We hypothesized chronic reductions in utero-placental perfusion (RUPP) for 5 days (d) during either mid- (d12-d17) or late (d14-d19) gestation would have disparate effects on plasma sFlt-1 and VEGF levels and blood pressure. Five days of chronic RUPP was achieved by placement of silver clips on the abdominal aorta and ovarian arteries on either gestational d12 or d14.

Placental and vascular adaptations to exercise training before and during pregnancy in the rat.

Although exercise during pregnancy is generally recommended and thought to be beneficial to mother and fetus, the nature of the adaptations to exercise during pregnancy and how they may be beneficial remain poorly understood. Recent studies suggest that exercise may stimulate expression of several cytoprotective and pro-angiogenic molecules such as heat shock proteins (HSP) and vascular endothelial growth factors (VEGF). We hypothesized that exercise training during pregnancy improves angiogenic balance, increases HSP expression, and improves endothelial function.

The opposing roles of anti-angiogenic factors in cancer and preeclampsia.

Hypertensive disorders of pregnancy such as preeclampsia present an increasing source of concern during gestation and accumulating evidence suggests there are long-term effects on the subsequent health of the mother and child. While formerly preeclamptic women have increased risk for later cardiovascular disease, they appear to have decreased risk of some cancers. Recent investigations have revealed exciting insights into potential mechanisms underlying the pathogenesis of preeclampsia and some of these findings may bear relevance to the attenuated cancer risk reported in the literature.

Proteins regulating cap-dependent translation are downregulated during total knee arthroplasty.

Total knee arthroplasty (TKA) utilizes a tourniquet to reduce blood loss, maintain a clear surgical "bloodless" field, and to ensure proper bone-implant cementing. In 2007, over 600,000 TKAs were performed in the United States, and this number is projected to increase to 3.48 million procedures performed annually by 2030.