TLR (Toll-Like Receptor) 4 Antagonism Prevents Left Ventricular Hypertrophy and Dysfunction Caused by Neonatal Hyperoxia Exposure in Rats
| Autor: | Anne Monique Nuyt, Muhammad Oneeb Rehman Mian, Thuy-An Mai-Vo, Rafael Oliveira Fernandes, Mariane Bertagnolli, Thuy Mai Luu, Fauve Boudreau, Ying He, Anik Cloutier |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Male Cardiac output medicine.medical_specialty Cardiac fibrosis 030204 cardiovascular system & hematology Hyperoxia Left ventricular hypertrophy Muscle hypertrophy Rats Sprague-Dawley 03 medical and health sciences Ventricular Dysfunction Left 0302 clinical medicine Internal medicine Internal Medicine Medicine Animals Ejection fraction business.industry medicine.disease Rats Toll-Like Receptor 4 Disease Models Animal 030104 developmental biology Blood pressure Endocrinology Animals Newborn Room air distribution Cytokines Hypertrophy Left Ventricular medicine.symptom business Reactive Oxygen Species |
| Zdroj: | Hypertension (Dallas, Tex. : 1979). 74(4) |
| ISSN: | 1524-4563 |
| Popis: | Preterm birth is associated with proinflammatory conditions and alterations in adult cardiac shape and function. Neonatal exposure to high oxygen, a rat model of prematurity-related conditions, leads to cardiac remodeling, fibrosis, and dysfunction. TLR (Toll-like receptor) 4 signaling is a critical link between oxidative stress, inflammation, and the pathogenesis of cardiovascular diseases. The current study sought to investigate the role of TLR4 signaling in neonatal oxygen-induced cardiomyopathy. Male Sprague-Dawley pups were kept in 80% oxygen or room air from day 3 to 10 of life and treated with TLR4 antagonist lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides (LPS-RS) or saline. Echocardiography was performed at 4, 7, and 12 weeks. At 12 weeks, intraarterial blood pressure was measured before euthanization for histological and biochemical analyses. At day 10, cardiac TLR4, Il (interleukin) 18, and Il1β expression were increased in oxygen-exposed compared with room air controls. At 4 weeks, compared with room air-saline, saline-, but not LPS-RS treated-, oxygen-exposed animals, exhibited increased left ventricle mass index, reduced ejection fraction, and cardiac output index. Findings were similar at 7 and 12 weeks. LPS-RS did not influence echocardiography in 12 weeks room air animals. Systolic blood pressure was higher in saline- but not LPS-RS treated-oxygen-exposed animals compared with room air-saline and -LPS-RS controls. LPS-RS prevented cardiac fibrosis and cardiomyocytes hypertrophy, the increased TLR4, Myd88, and Il18 gene expression, TRIF expression, and CD68+ macrophages infiltration associated with neonatal oxygen exposure, without impact in room air rats. This study indicates that neonatal exposure to high oxygen programs TLR4 activation, which contributes to cardiac remodeling and dysfunction. |
| Databáze: | OpenAIRE |
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