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Mechanisms underlying early development of pulmonary vascular obstructive disease in Down syndrome: An imbalance in biosynthesis of thromboxane A 2 and prostacyclin
Author(s) -
Fukushima Hiroyuki,
Kosaki Kenjiro,
Sato Reiko,
Yagihashi Tatsuhiko,
Gatayama Ryohei,
Kodo Kazuki,
Hayashi Takuya,
Nakazawa Maki,
Tsuchihashi Takatoshi,
Maeda Jun,
Kojima Yoshifumi,
Yamagishi Hiroyuki,
Takahashi Takao
Publication year - 2010
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33555
Subject(s) - prostacyclin , pulmonary hypertension , thromboxane , medicine , endocrinology , thromboxane a2 , hypoxic pulmonary vasoconstriction , pathophysiology , excretion , biosynthesis , vasoconstriction , urinary system , cardiology , chemistry , biochemistry , platelet , enzyme
Patients with Down syndrome (DS) and a left‐to‐right shunt often develop early severe pulmonary hypertension (PH) and pulmonary vascular obstructive disease (PVOD); the pathophysiological mechanisms underlying the development of these complications are yet to be determined. To investigate the mechanisms, we evaluated the biosynthesis of thromboxane (TX) A 2 and prostacyclin (PGI 2 ) in four groups of infants, cross‐classified as shown below, by measuring the urinary excretion levels of 11‐dehydro‐TXB 2 and 2,3‐dinor‐6‐keto‐PGF 1α : DS infants with a left‐to‐right shunt and PH (D‐PH, n = 18), DS infants without congenital heart defect (D‐C, n = 8), non‐DS infants with a left‐to‐right shunt and PH (ND‐PH, n = 12), and non‐DS infants without congenital heart defect (ND‐C, n = 22). The urinary excretion ratios of 11‐dehydro‐TXB 2 to 2,3‐dinor‐6‐keto‐PGF 1α in the D‐PH, D‐C, ND‐PH, and ND‐C groups were 7.69, 4.71, 2.10, and 2.27, respectively. The ratio of 11‐dehydro‐TXB 2 to 2,3‐dinor‐6‐keto‐PGF 1α was higher in the presence of DS ( P < 0.001), independently of the presence of PH ( P = 0.297). The predominant biosynthesis of TXA 2 over PGI 2 , leading to vasoconstriction, was observed in DS infants, irrespective of the presence/absence of PH. This imbalance in the biosynthesis of vasoactive eicosanoids may account for the rapid progression of PVOD in DS infants with a left‐to‐right shunt. © 2010 Wiley‐Liss, Inc.