Comparison of endothelial biomarkers according to reversibility of pulmonary hypertension secondary to congenital heart disease.
The reversibility of pulmonary arterial hypertension (PAH) in children with congenital heart disease (CHD) is strongly associated with the degree of intimal proliferation, vessel narrowing, and number of circulating endothelial cells (CECs). Circulating endothelial cells may arise from either endothelial damage or accelerated turnover during vessel remodeling, but nothing is known about endothelial microparticles (EMPs) and other biomarkers reflecting endothelial alterations. This study aimed to document endothelial markers further according to the irreversibility of PAH secondary to CHD. The study investigated soluble markers of endothelial damage or activation (thrombomodulin, soluble endothelial protein C receptor, and soluble E-selectin), inflammation (interleukin-6), and angiogenic cytokine levels [vascular endothelial growth factor (VEGF) and placental growth factor (PlGF)] in 26 patients with CHD, 16 with reversible PAH (median age, 2 years) and 10 with irreversible PAH (median age, 9 years). Endothelial activation/apoptosis was evaluated by measuring EMP levels. Plasma procoagulant activity also was measured. The results show that the levels of soluble markers indicating endothelial activation were not predictors of PAH irreversibility. Lower levels of PlGF were observed in reversible compared with irreversible PAH but were not associated with the CEC level, the mean pulmonary artery pressure (mPAP), or age. No significant difference in procoagulant activity or EMP level was found between irreversible and reversible PAH. Among a large panel of biomarkers reflecting endothelial activation, regeneration, and injury, the high CEC levels previously described proved to be the only marker allowing discrimination between reversible and irreversible PAH secondary to CHD.
Smadja
David M
DM
Université Paris Descartes, Paris, France. david.smadja@egp.aphp.fr
Gaussem
Pascale
P
Mauge
Laetitia
L
Lacroix
Romaric
R
Gandrille
Sophie
S
Remones
Véronique
V
Peyrard
Séverine
S
Sabatier
Florence
F
Bonnet
Damien
D
Lévy
Marilyne
M
D000367:Age Factors; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D014655:Vascular Resistance / Q000502:physiology
D015415:Biomarkers