TY - JOUR
T1 - Umbilical cord blood metabolomics reveal distinct signatures of dyslipidemia prior to bronchopulmonary dysplasia and pulmonary hypertension
AU - La Frano, Michael R.
AU - Fahrmann, Johannes F.
AU - Grapov, Dmitry
AU - Pedersen, Theresa L.
AU - Newman, John W.
AU - Fiehn, Oliver
AU - Underwood, Mark A.
AU - Mestan, Karen
AU - Steinhorn, Robin H.
AU - Wedgwood, Stephen
N1 - Funding Information:
This research is funded by National Institutes of Heath (NIH) Grants U24-DK-097154 (to O. Fiehn) and K23-HL-093302 (to K. Mestan), with instrument support by S10-RR-031630 (to O. Fiehn) and by US Department of Agriculture Intramural Project 2032-51530-022-00D (to J. W. Newman).
Publisher Copyright:
© 2018 American Physiological Society.
PY - 2018/11
Y1 - 2018/11
N2 - Pulmonary hypertension (PH) is a common consequence of bronchopulmonary dysplasia (BPD) and remains a primary contributor to increased morbidity and mortality among preterm infants. Unfortunately, at the present time, there are no reliable early predictive markers for BPD-associated PH. Considering its health consequences, understanding in utero perturbations that lead to the development of BPD and BPD-associated PH and identifying early predictive markers is of utmost importance. As part of the discovery phase, we applied a multiplatform metabolomics approach consisting of untargeted and targeted methodologies to screen for metabolic perturbations in umbilical cord blood (UCB) plasma from preterm infants that did (n ☓ 21; cases) or did not (n ☓ 21; controls) develop subsequent PH. A total of 1,656 features were detected, of which 407 were annotated by metabolite structures. PH-associated metabolic perturbations were characterized by reductions in major choline-containing phospholipids, such as phosphatidylcholines and sphingomyelins, indicating altered lipid metabolism. The reduction in UCB abundances of major choline-containing phospholipids was confirmed in an independent validation cohort consisting of UCB plasmas from 10 cases and 10 controls matched for gestational age and BPD status. Subanalyses in the discovery cohort indicated that elevations in the oxylipins PGE1, PGE2, PGF2a, 9-and 13-HOTE, 9-and 13-HODE, and 9-and 13-KODE were positively associated with BPD presence and severity. This expansive evaluation of cord blood plasma identifies compounds reflecting dyslipidemia and suggests altered metabolite provision associated with metabolic immaturity that differentiate subjects, both by BPD severity and PH development.
AB - Pulmonary hypertension (PH) is a common consequence of bronchopulmonary dysplasia (BPD) and remains a primary contributor to increased morbidity and mortality among preterm infants. Unfortunately, at the present time, there are no reliable early predictive markers for BPD-associated PH. Considering its health consequences, understanding in utero perturbations that lead to the development of BPD and BPD-associated PH and identifying early predictive markers is of utmost importance. As part of the discovery phase, we applied a multiplatform metabolomics approach consisting of untargeted and targeted methodologies to screen for metabolic perturbations in umbilical cord blood (UCB) plasma from preterm infants that did (n ☓ 21; cases) or did not (n ☓ 21; controls) develop subsequent PH. A total of 1,656 features were detected, of which 407 were annotated by metabolite structures. PH-associated metabolic perturbations were characterized by reductions in major choline-containing phospholipids, such as phosphatidylcholines and sphingomyelins, indicating altered lipid metabolism. The reduction in UCB abundances of major choline-containing phospholipids was confirmed in an independent validation cohort consisting of UCB plasmas from 10 cases and 10 controls matched for gestational age and BPD status. Subanalyses in the discovery cohort indicated that elevations in the oxylipins PGE1, PGE2, PGF2a, 9-and 13-HOTE, 9-and 13-HODE, and 9-and 13-KODE were positively associated with BPD presence and severity. This expansive evaluation of cord blood plasma identifies compounds reflecting dyslipidemia and suggests altered metabolite provision associated with metabolic immaturity that differentiate subjects, both by BPD severity and PH development.
KW - Bronchopulmonary dysplasia
KW - Lipids
KW - Metabolomics
KW - Oxylipins
KW - Pulmonary hypertension
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U2 - 10.1152/ajplung.00283.2017
DO - 10.1152/ajplung.00283.2017
M3 - Article
C2 - 30113229
AN - SCOPUS:85059741915
SN - 1040-0605
VL - 315
SP - L870-L881
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 5
ER -