[109] Pre-eclampsia is a pregnancy-related syndrome that

[109] Pre-eclampsia is a pregnancy-related syndrome that buy Tyrosine Kinase Inhibitor Library affects multiple systems and clinically presents as hypertension, proteinuria, edema, and in its more sever forms evidence

of fetal compromise, neurologic abnormality, liver and hematologic dysfunction.[110] The complexity of the syndrome defies the development of a panel of genetic screens or biomarkers.[111] While the basic cause of the disease is as yet unknown, multiple hypotheses exist. These include failure of placentation[112] and thus reduced utero-placental perfusion, intolerance to volume expansion generated by pregnancy,[113] infection,[114] and inflammation.[115] It is hotly debated as to whether failed placentation is caused or a by-product of broken maternal immune tolerance.[116, 117] Many agree that a common final pathway to the manifestation of the disease is endothelial cell damage occurring in a variety of vascular beds.[118] While the Deforolimus cell line disease is thought of as being unique in human, many recognize the potential positive role of the integration of research in human and animal models in understanding the underlying mechanisms.[119, 120] The hallmarks of pre-eclampsia most sought

after in animal models are hypertension, renal dysfunction (proteinuria), and further, conditions such as poor trophoblast invasion and endothelial damage. Current models address some of these issues. There have been rare reports of spontaneous pre-eclampsia in related non-human primates.[121] These species have also been used to develop models of pregnancy-related hypertension and proteinuria based on injection during mid-gestation of inflammatory mediators, such as tumor necrosis factor[122] or antibodies to interleukin 10.[123] There are strains of mice that spontaneously develop hypertension, proteinuria, smaller litters, and fetal demise, and these have been used to model pre-eclampsia.[124, Methisazone 125] There are also models of spontaneous pregnancy-associated hypertension with fetal compromise

in rats.[126] There also exist genetically manipulated mouse and rat models. In one interesting genetic model of hypertension in pregnancy, female mice transgenic for human angiotensinogen are mated to males transgenic for human rennin.[127] The resulting pregnancy is marked by distortion of placental anatomy, elevation of circulation vascular endothelial growth factor (VEGF) receptor in mid-gestation (12–13 of 19–20 days), hypertension, fetal intrauterine growth retardation, and systemic maternal disorders including proteinuria and convulsion. In the rat version of this model,[128] the hypertensive disease experienced by the pregnant rat is thought related to secretion of rennin from the placenta into the maternal circulation.

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