The protective effect of apolipoprotein in models of trophoblast invasion and preeclampsia.
Preeclampsia is a hypertensive disorder of pregnancy. It is associated with abnormal placentation via poor placental invasion of the uterine vasculature by trophoblast cells, leading to poor placental perfusion, oxidative stress, and inflammation, all of which are implicated in its pathogenesis. A dyslipidemia characterized by low plasma levels of high-density lipoproteins (HDL) and elevated triglycerides has been described in preeclampsia. Apolipoprotein A-I (apoA-I), a constituent of HDL is an anti-inflammatory agent. This study investigated whether apoA-I protects against hypertension and adverse placental changes in a proinflammatory cytokine (TNF-α)-induced model of preeclampsia. Further, this study investigated whether apoA-I protects against the inhibitory effect of TNF-α in a human in vitro model of trophoblast invasion. Administration of apoA-I to pregnant mice before infusion with TNF-α resulted in a significant reduction in the cytokine-induced increase in systolic blood pressure. MRI measurement of T2relaxation, a parameter that is tissue specific and sensitive to physiological changes within tissues, showed a reversal of TNF-α-induced placental changes. Preincubation of endothelial cells with apoA-I protected against the TNF-α-induced inhibition of HTR-8/SVneo (trophoblast) cell integration into endothelial (UtMVEC) networks. These data suggest that a healthy lipid profile may affect pregnancy outcomes by priming endothelial cells in preparation for trophoblast invasion.
Vascular Immunology Group, The Heart Research Institute, Sydney, New South Wales, Australia.|Lipid Research Group, The Heart Research Institute, Sydney, New South Wales, Australia.|Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Francesca
F
Charlton
School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.|Nanoscale Organisation and Dynamics, School of Science and Health, Western Sydney University, Penrith, New South Wales, Australia; and.
Gabriele
0000-0002-8179-2278
G
Bobek
School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.|Nanoscale Organisation and Dynamics, School of Science and Health, Western Sydney University, Penrith, New South Wales, Australia; and.
Tim
T
Stait-Gardner
School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.|Nanoscale Organisation and Dynamics, School of Science and Health, Western Sydney University, Penrith, New South Wales, Australia; and.
William S
WS
Price
Department of Physiology, Monash University, Melbourne, Victoria, Australia.
Katrina M
KM
Mirabito Colafella
Vascular Immunology Group, The Heart Research Institute, Sydney, New South Wales, Australia.|School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.
Bei
B
Xu
Vascular Immunology Group, The Heart Research Institute, Sydney, New South Wales, Australia.
Angela
A
Makris
Lipid Research Group, The Heart Research Institute, Sydney, New South Wales, Australia.|Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.|Centre for Vascular Research, University of New South Wales, Sydney, New South Wales, Australia.
Kerry-Anne
KA
Rye
Vascular Immunology Group, The Heart Research Institute, Sydney, New South Wales, Australia; An.Hennessy@westernsydney.edu.au.|School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.|Nanoscale Organisation and Dynamics, School of Science and Health, Western Sydney University, Penrith, New South Wales, Australia; and.
Annemarie
A
Hennessy
D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
D016632:Apolipoprotein A-I; D015815:Cell Adhesion Molecules; D014409:Tumor Necrosis Factor-alpha
apolipoprotein A-I; hypertension in pregnancy; magnetic resonance imaging; preeclampsia; trophoblast invasion