Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 133, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2020.111081
Keywords
Pulmonary arterial hypertension; Inflammation; Monocrotaline; PI3K/Akt
Funding
- National Natural Science Foundation of China [U1812403]
- Initiation Fund for Excellent Doctor of Zunyi Medical University [F-951]
- Opening Subject of Key Laboratory of Basic Pharmacology of Ministry of Education
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Inflammation plays a significant role in the pathogenesis of PAH. The study found that PAH induced by MCT progresses from an acute inflammatory phase to a chronic inflammatory phase, with changes in pro-inflammatory cytokines and macrophage ratios in the lung. The PI3K/Akt signaling pathway is also related to the progression of PAH and inflammation characteristics induced by MCT.
Objective: A growing evidence demonstrates that inflammation is a major contributor to the pathogenesis of pulmonary arterial hypertension (PAH). However, blocking inflammation has only been shown to be of minor clinical benefit due to a lack of understanding of the precise inflammation present in PAH. Thus, the present study aimed to investigate characteristics of inflammatory process in PAH induced by monocrotaline (MCT) in rats. Methods: Adult male Sprague-Dawley rats received a single dose of MCT (50 mg/kg, ip), and the occurrence of PAH and inflammation biomarkers were measured at 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30 days after MCT injection. Results: From the 6th day after the injection of MCT, the mean pulmonary artery pressure gradually increased and doubled on the 30th day, accompanied by right ventricular hypertrophy and pulmonary arterial remodeling in a time-dependent manner. In the first 6 days after MCT treatment, only pro-inflammatory cytokines TNF-alpha, IL-1 beta increased, which was defined as acute inflammatory phase, after that, both pro-inflammatory factors TNF-alpha, IL-1 beta, IL-6, IL-12 and anti-inflammatory factors Arg1, IL-10, TGF-13 increased, which was defined as chronic inflammatory phase. The M1/M2 macrophage ratios in lung and alveolar lavage fluid were elevated on the 6th and 30th day, moreover, which were higher on the 6th than 30th day, and the PI3K/Akt signaling pathway increased along with the progression of PAH and correlated with pro-inflammatory proteins, which revealed also to some extent the characteristics of inflammation of PAH induced by MCT. Conclusion: The course of PAH induced by MCT injection is progressive with persistent inflammation, which is defined as acute inflammatory phase within 6 days after MCT treatment, after that, is defined as chronic inflammatory phase.
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