Deficiency in ST2 signaling ameliorates RSV-associated pulmonary hypertension

Luan D. Vu, Jordy Saravia, Sridhar Jaligama, Rajshri V.Baboeram Panday, Ryan D. Sullivan, Salvatore Mancarella, Stephania A. Cormier, Dai Kimura

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Pulmonary hypertension (PH) observed during respiratory syncytial virus (RSV) bronchiolitis is associated with morbidity and mortality, especially in children with congenital heart disease. Yet, the pathophysiological mechanisms of RSV-associated PH remain unclear. Therefore, this study aimed to investigate the pathophysiological mechanism of RSV-associated PH. We used a translational mouse model of RSV-associated PH, in which wild-type (WT) and suppression of tumorigenicity 2 (ST2) knockout neonatal mice were infected with RSV at 5 days old and reinfected 4 wk later. The development of PH in WT mice following RSV reinfection was evidenced by elevated right ventricle systolic pressure, shortened pulmonary artery acceleration time (PAT), and decreased PAT/ejection time (ET) ratio. It coincided with the augmentation of periostin and IL-13 expression and increased arginase bioactivity by both arginase 1 and 2 as well as induction of nitric oxide synthase (NOS) uncoupling. Absence of ST2 signaling prevented RSV-reinfected mice from developing PH by suppressing NOS uncoupling. In summary, ST2 signaling was involved in the development of RSV-associated PH. ST2 signaling inhibition may be a novel therapeutic target for RSV-associated PH. NEW & NOTEWORTHY We report that the pathogenic role of ST2-mediated type 2 immunity and mechanisms contribute to RSV-associated pulmonary hypertension. Inhibiting ST2 signaling may be a novel therapeutic target for this condition.

Original languageEnglish (US)
Pages (from-to)H309-H317
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume321
Issue number2
DOIs
StatePublished - Aug 2021
Externally publishedYes

Keywords

  • Arginase
  • Periostin
  • Pulmonary hypertension
  • Respiratory syncytial virus
  • ST2

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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