title: Association of Maternal Antiangiogenic Profile at Birth With Early Postnatal Loss of Microvascular Density in Offspring of Hypertensive Pregnancies.
abstract: Offspring of hypertensive pregnancies are more likely to have microvascular rarefaction and increased blood pressure in later life. We tested the hypothesis that maternal angiogenic profile during a hypertensive pregnancy is associated with fetal vasculogenic capacity and abnormal postnatal microvascular remodeling. Infants (n=255) born after either hypertensive or normotensive pregnancies were recruited for quantification of postnatal dermal microvascular structure at birth and 3 months of age. Vasculogenic cell potential was assessed in umbilical vein endothelial cells from 55 offspring based on in vitro microvessel tube formation and proliferation assays. Maternal angiogenic profile (soluble fms-like tyrosine kinase-1, soluble endoglin, vascular endothelial growth factor, and placental growth factor) was measured from postpartum plasma samples to characterize severity of pregnancy disorder. At birth, offspring born after hypertensive pregnancy had similar microvessel density to those born after a normotensive pregnancy, but during the first 3 postnatal months, they had an almost 2-fold greater reduction in total vessel density (-17.7±16.4% versus -9.9±18.7%; P=0.002). This postnatal loss varied according to the vasculogenic capacity of the endothelial cells of the infant at birth (r=0.49; P=0.02). The degree of reduction in both in vitro and postnatal in vivo vascular development was proportional to levels of antiangiogenic factors in the maternal circulation. In conclusion, our data indicate that offspring born to hypertensive pregnancies have reduced vasculogenic capacity at birth that predicts microvessel density loss over the first 3 postnatal months. Degree of postnatal microvessel reduction is proportional to levels of antiangiogenic factors in the maternal circulation at birth.
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.).
authors.forename: Grace Z
authors.initials: GZ
authors.lastname: Yu
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.).
authors.forename: Christina Y L
authors.initials: CY
authors.lastname: Aye
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.).
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Lewandowski
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.).
authors.forename: Esther F
authors.initials: EF
authors.lastname: Davis
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.).
authors.forename: Cheen P
authors.initials: CP
authors.lastname: Khoo
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.).
authors.forename: Laura
authors.initials: L
authors.lastname: Newton
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.).
authors.forename: Cheng T
authors.initials: CT
authors.lastname: Yang
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.).
authors.forename: Ayman
authors.initials: A
authors.lastname: Al Haj Zen
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.).
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Simpson
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.).
authors.forename: Kathryn
authors.initials: K
authors.lastname: O'Brien
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.).
authors.forename: David A
authors.initials: DA
authors.lastname: Cook
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.).
authors.forename: Ingrid
authors.initials: I
authors.lastname: Granne
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.).
authors.forename: Theodosios
authors.initials: T
authors.lastname: Kyriakou
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.).
authors.forename: Keith M
authors.initials: KM
authors.lastname: Channon
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.).
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Watt
authors.affiliation: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (G.Z.Y., C.Y.L.A., A.J.L., E.F.D., L.N., A.A.H.Z., L.J.S., K.O'B., T.K., K.M.C., P.L.), Stem Cell Research, Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences and National Health Service Blood and Transplant (G.Z.Y., C.P.K., L.N., C.T.Y., L.J.S., D.A.C., S.M.W.), Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division (C.Y.L.A., I.G.), and Wellcome Trust Centre for Human Genetics (A.A.H.Z., T.K.), University of Oxford, United Kingdom; and Peninsula Schools of Medicine and Dentistry, Plymouth University, United Kingdom (K.O'B.). paul.leeson@cardiov.ox.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Leeson
mesh_terms: D000328:Adult; D015331:Cohort Studies; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D047109:Fetal Development / Q000502:physiology; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000503:physiopathology*; D007223:Infant; D007231:Infant, Newborn; D055806:Microvessels / Q000254:growth & development*; D000072483:Placenta Growth Factor / Q000378:metabolism; D011225:Pre-Eclampsia / Q000503:physiopathology; D011237:Predictive Value of Tests; D011247:Pregnancy; D011256:Pregnancy Outcome; D011257:Pregnancy Proteins / Q000097:blood; D047928:Premature Birth / Q000209:etiology / Q000503:physiopathology; D012189:Retrospective Studies; D018570:Risk Assessment; D014471:Umbilical Veins / Q000196:embryology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
chemical_list: D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: embryonic ad fetal development human umbilical vein endothelial cells infant, newborn microvessels preeclampsia premature birth vascular endothelial growth factor receptor-1