Animal models of pre-eclampsia.
The cardinal features of human pre-eclampsia, hypertension and proteinuria, are mimicked in animal models. Increasingly, the accuracy of inducing 'pure' systemic endothelial dysfunction is regarded as critical in differentiating mechanisms of pre-eclampsia from other conditions which induce hypertension (e.g. glomerulonephritis, renal denervation or manipulation of the renin-angiotensin system). A recent study in baboons has identified the timing of induction of maternal endothelial damage after acute uteroplacental ischaemia (UPI). The endothelial changes in the glomerulus are indicative of a direct endothelial toxin and mimic the lesions seen in human pre-eclampsia; the extent of hypertension and proteinuria are also similar. This animal model identifies systemic and placental sFLT-1 (soluble fms-like tyrosine kinase-1) as a potential mediator of endothelial damage. This research involving primates with haemomonochorial placentas makes translation of these results to humans very compelling for understanding the mechanisms of human disease. Similar endothelial dysfunction has been identified in baboons treated with anti-inflammatory inhibitors. Similar studies in rodents have identified a relationship between angiotensin II agonistic antibodies, UPI/reduced uteroplacental perfusion pressure, angiogenic markers, and cytokines. We can now identify vasoconstrictive mediators of the hypertensive and endothelial response such as endothelin 1, the renin-angiotensin system, or other hormones such as oestrogens in primate models.
Heart Research Institute, Sydney, Australia.
Neroli
N
Sunderland
Annemarie
A
Hennessy
Angela
A
Makris
D000804:Angiotensin II / Q000819:agonists / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004195:Disease Models, Animal; D004727:Endothelium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology*; D021041:Placental Circulation; D011225:Pre-Eclampsia / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000804:Angiotensin II; D040281:Vascular Endothelial Growth Factor Receptor-1