Maternal and foetal angiogenic imbalance in congenital heart defects

被引：112

作者：

Llurba, Elisa ^{[1
,2
]}

Sanchez, Olga ^{[2
,3
]}

Ferrer, Queralt ^{[4
]}

Nicolaides, Kypros H. ^{[5
,6
]}

Ruiz, Aina ^{[1
,2
]}

Dominguez, Camen ^{[3
,7
]}

Sanchez-de-Toledo, Joan ^{[8
]}

Garcia-Garcia, Belen ^{[1
,2
]}

Soro, Gemma ^{[1
,2
]}

Arevalo, Silvia ^{[1
]}

Goya, Maria ^{[1
,2
]}

Suy, Anna ^{[1
,2
]}

Perez-Hoyos, Santiago ^{[9
]}

Alijotas-Reig, Jaume ^{[10
]}

Carreras, Elena ^{[1
,2
]}

Cabero, Lluis ^{[1
,2
]}

机构：

[1] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Dept Obstet, Maternal Foetal Med Unit, E-08193 Barcelona, Spain

[2] Inst Salud Carlos III, Maternal & Child Hlth & Dev Network SAMID RD12 00, CIBER ER, Madrid, Spain

[3] Vall Hebron Inst Res VHIR, Biochem & Mol Biol Res Ctr Nanomed CIBBIM, Barcelona, Spain

[4] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Dept Paediat, Paediat Cardiol Unit, E-08193 Barcelona, Spain

[5] Kings Coll Hosp London, Harris Birthright Res Ctr Foetal Med, London, England

[6] Univ Coll London Hosp, Dept Foetal Med, London, England

[7] Ctr Biomed Res Rare Dis CIBERER, Barcelona, Spain

[8] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Dept Paediat, Paediat Cardiac Intens Care Unit, E-08193 Barcelona, Spain

[9] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Dept Epidemiol & Prevent Med, USMIB Unitat Suport Recerca Biomed, E-08193 Barcelona, Spain

[10] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Syst Autoimmune Dis Unit, Serv Internal Med 1, E-08193 Barcelona, Spain

来源：

EUROPEAN HEART JOURNAL | 2014年 / 35卷 / 11期

关键词：

Congenital heart defects; Placental growth factor; sFlt-1; Vascular endothelial growth factor; Soluble endoglin; ENDOTHELIAL GROWTH-FACTOR; AORTIC-VALVE DISEASE; CEREBRAL-BLOOD-FLOW; CARDIOVASCULAR MALFORMATIONS; PULSATILITY INDEX; NOTCH1; MUTATIONS; BIRTH-WEIGHT; FETUSES; CARDIOMYOPATHY; EXPRESSION;

D O I：

10.1093/eurheartj/eht389

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aims Animal models showed that angiogenesis is related to abnormal heart development. Our objectives were to ascertain whether a relationship exists between congenital heart defects (CHDs) and angiogenic/anti-angiogenic imbalance in maternal and foetal blood and study the expression of angiogenic factors in the foetal heart. Methods and Results Maternal and cord blood placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were compared in 65 cases of CHD and 204 normal controls. Angiogenic factor expression and markers of hypoxia were measured in heart tissue from 23 CHD foetuses and 8 controls. In the CHD group, compared with controls, plasma PlGF levels were significantly lower (367 33 vs. 566 26 pg/mL; P 0.0001) and sFlt-1 significantly higher (2726 450 vs. 1971 130 pg/mL, P 0.0438). Foetuses with CHD had higher cord plasma sFlt-1 (442 76 vs. 274 26 pg/mL; P 0.0285) and sEng (6.76 0.42 vs. 4.99 0.49 ng/mL, P 0.0041) levels. Expression of vascular endothelial growth factor (VEGF), sFlt-1, markers of chronic hypoxia, and antioxidant activity were significantly higher in heart tissue from CHD foetuses compared with normal hearts (VEGF, 1.59-fold; sFlt-1, 1.92-fold; hypoxia inducible factor (HIF)-2, 1.45-fold; HO-1, 1.62-fold; SOD1, 1.31-fold). Conclusion An intrinsically angiogenic impairment exists in CHD that appears to be present in both the maternal and foetal circulation and foetal heart. Our data suggest that an imbalance of angiogenic-antiangiogenic factors is associated with developmental defects of the human heart.

引用

页码：701 / +

页数：8

共 47 条

[1] Placental Growth Factor as a Protective Paracrine Effector in the Heart [J].

Accornero, Federica ;

Molkentin, Jeffery D. .

TRENDS IN CARDIOVASCULAR MEDICINE, 2011, 21 (08) :220-224

[2] Prediction of early, intermediate and late pre-eclampsia from maternal factors, biophysical and biochemical markers at 11-13 weeks [J].

Akolekar, Ranjit ;

Syngelaki, Argyro ;

Sarquis, Rita ;

Zvanca, Mona ;

Nicolaides, Kypros H. .

PRENATAL DIAGNOSIS, 2011, 31 (01) :66-74

[3] Cerebral blood flow autoregulation and congenital heart disease: possible causes of abnormal prenatal neurologic development [J].

Arduini, Maurizio ;

Rosati, Paolo ;

Caforio, Leonardo ;

Guariglia, Lorenzo ;

Clerici, Graziano ;

Di Renzo, Gian Carlo ;

Scambia, Giovanni .

JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE, 2011, 24 (10) :1208-1211

[4] Heart valve development - Endothelial cell signaling and differentiation [J].

Armstrong, EJ ;

Bischoff, J .

CIRCULATION RESEARCH, 2004, 95 (05) :459-470

[5] Doppler indices of the middle cerebral artery in fetuses with cardiac defects theoretically associated with impaired cerebral oxygen delivery in utero: is there a brain-sparing effect? [J].

Berg, C. ;

Gembruch, O. ;

Gembruch, U. ;

Geipel, A. .

ULTRASOUND IN OBSTETRICS & GYNECOLOGY, 2009, 34 (06) :666-672

[6] Early endocardial morphogenesis requires Scl/Tal1 [J].

Bussmann, Jeroen ;

Bakkers, Jeroen ;

Schulte-Merker, Stefan .

PLOS GENETICS, 2007, 3 (08) :1425-1437

[7] Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188 [J].

Carmeliet, P ;

Ng, YS ;

Nuyens, D ;

Theilmeier, G ;

Brusselmans, K ;

Cornelissen, I ;

Ehler, E ;

Kakkar, VV ;

Stalmans, I ;

Mattot, V ;

Perriard, JC ;

Dewerchin, M ;

Flameng, W ;

Nagy, A ;

Lupu, F ;

Moons, L ;

Collen, D ;

D'Amore, PA ;

Shima, DT .

NATURE MEDICINE, 1999, 5 (05) :495-502

[8] Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions [J].

Carmeliet, P ;

Moons, L ;

Luttun, A ;

Vincenti, V ;

Compernolle, V ;

De Mol, M ;

Wu, Y ;

Bon, F ;

Devy, L ;

Beck, H ;

Scholz, D ;

Acker, T ;

DiPalma, T ;

Dewerchin, M ;

Noel, A ;

Stalmans, I ;

Barra, A ;

Blacher, S ;

Vandendriessche, T ;

Ponten, A ;

Eriksson, U ;

Plate, KH ;

Foidart, JM ;

Schaper, W ;

Charnock-Jones, DS ;

Hicklin, DJ ;

Herbert, JM ;

Collen, D ;

Persico, MG .

NATURE MEDICINE, 2001, 7 (05) :575-583

[9] Autoregulation of cerebral blood flow in fetuses with congenital heart disease: The brain sparing effect [J].

Donofrio, MT ;

Bremer, YA ;

Schieken, RM ;

Gennings, C ;

Morton, LD ;

Eidem, BW ;

Cetta, F ;

Falkensammer, CB ;

Huhta, JC ;

Kleinman, CS .

PEDIATRIC CARDIOLOGY, 2003, 24 (05) :436-443

[10] The expression patterns of hypoxia-inducing factor subunit α-1, heme oxygenase, hypoxia upregulated protein 1, and cardiac troponin T during development of the chicken heart [J].

Druyan, S. ;

Cahaner, A. ;

Ashwell, C. M. .

POULTRY SCIENCE, 2007, 86 (11) :2384-2389

← 1 2 3 4 5 →