Toll-like receptor 4deficient mice are resistant to chronic hypoxia-induced pulmonary hypertension

Karen C. Young, Sameh M.A. Hussein, Rita Dadiz, Daphne Demello, Carlos Devia, Dorothy Hehre, Cleide Suguihara

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Current data suggest that Toll-like receptor 4 (TLR4), a key molecule in the innate immune response, may also be activated following tissue injury. Activation of this receptor is known to induce the production of several proinflammatory cytokines. Given that pulmonary inflammation has been shown to be a key contributor to chronic hypoxia-induced pulmonary vascular remodeling, the authors hypothesized that TLR4-deficient mice would be less susceptible to pulmonary hypertension (PH) as compared to mice with intact TLR4. TLR4-deficient and TLR4-intact strains of inbred mice were exposed to 4, 8, and 16 weeks of hypoxia (0.10 FiO2) or normoxia (0.21 FiO2) in a normobaric chamber. After chronic hypoxic exposure, TLR4-intact mice developed significant PH evidenced by increased right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary artery medial thickening. In contrast, TLR4-deficient mice had no significant change in any of these parameters and this was associated with decreased pulmonary vascular inflammatory response as compared to the TLR4-intact mice. These results suggest that TLR4 deficiency may decrease the susceptibility to developing PH by attenuating the pulmonary vascular inflammatory response to chronic hypoxia.

Original languageEnglish (US)
Pages (from-to)111-119
Number of pages9
JournalExperimental Lung Research
Volume36
Issue number2
DOIs
StatePublished - Mar 15 2010

Keywords

  • Chronic hypoxia
  • Pulmonary hypertension
  • Toll-like receptor 4
  • Vascular remodeling

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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