Mechanisms underlying early development of pulmonary vascular obstructive disease in Down syndrome: An imbalance in biosynthesis of thromboxane A 2 and prostacyclin

Hiroyuki Fukushima, Kenjiro Kosaki, Reiko Sato, Tatsuhiko Yagihashi, Ryohei Gatayama, Kazuki Kodo, Takuya Hayashi, Maki Nakazawa, Takatoshi Tsuchihashi, Jun Maeda, Yoshifumi Kojima, Hiroyuki Yamagishi, Takao Takahashi

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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) A2 and prostacyclin (PGI2) in four groups of infants, cross -classified as shown below, by measuring the urinary excretion levels of 11-dehydro-TXB2 and 2,3-dinor-6-keto-PGF: 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-TXB2 to 2,3-dinor-6-keto-PGF 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-TXB2 to 2,3-dinor-6-keto- PGF was higher in the presence ofDS (P<0.001), independently of the presence of PH (P=0.297). The predominant biosynthesis of TXA2 over PGI2, leading to vaso-constriction, 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.

Original languageEnglish
Pages (from-to)1919-1924
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Issue number8
Publication statusPublished - 2010 Aug



  • Down syndrome
  • Prostacyclin
  • Pulmonary hypertension
  • Thromboxane A

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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