Jian Xu1, Jingjing Wang2, Chengjie Shao1, Xiaoning Zeng1, Lixiang Sun1, Hui Kong1, Weiping Xie1, Hong Wang1. 1. Department of Respiratory & Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. 2. Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
Abstract
BACKGROUND: In patients with pulmonary arterial hypertension (PAH), mast cells (MCs) are extensively observed around pulmonary vessels. However, their temporal and spatial variation during PAH development remains obscure. This study investigated the dynamic evolution of MCs in lungs and right ventricles (RV) to illuminate their role in pulmonary vascular and RV remodeling. METHODS: The PAH model was established by a single intra-peritoneal injection of monocrotaline (MCT, 60 mg/kg) in rats. On day 0, 3, 7, 14, and 28 after MCT injection, lung and RV tissues were harvested for staining with hematoxylin and eosin (HE), Gomori aldehyde fuchsin (GAF), toluidine blue (TB) and picrosirius red (PSR). Immunohistochemistry was performed to evaluate the levels of α-SMA, CD68 and tryptase. A simple RV remolding model was produced as well by pulmonary artery banding (PAB). RV tissues were collected to determine the degree of MCs infiltration. RESULTS: After MCT challenge, elevated mean pulmonary arterial pressure (mPAP), increased RV systolic pressure (RVSP), pulmonary arterial media hypertrophy as well as distal vascular muscularization gradually occurred with time. MCs recruitment along with CD68+ macrophages accumulation was observed around distal pulmonary vessels and in alveolar septa. Excessive infiltration and degranulation of MCs were detected in MCT-treated group in lung tissues but not in RV. In addition, no exacerbation of MCs infiltration and degranulation in RV was noted in PAB-treated rats, suggesting few contributions of MCs to RV remodeling. CONCLUSIONS: Our findings implied a crucial role of MCs in the remodeling of pulmonary vessels, not RV, which probably through releasing cytokines such as tryptase. The present study enriches the knowledge about PAH, providing a potential profile of MCs as a switch for the treatment of PAH.
BACKGROUND: In patients with pulmonary arterial hypertension (PAH), mast cells (MCs) are extensively observed around pulmonary vessels. However, their temporal and spatial variation during PAH development remains obscure. This study investigated the dynamic evolution of MCs in lungs and right ventricles (RV) to illuminate their role in pulmonary vascular and RV remodeling. METHODS: The PAH model was established by a single intra-peritoneal injection of monocrotaline (MCT, 60 mg/kg) in rats. On day 0, 3, 7, 14, and 28 after MCT injection, lung and RV tissues were harvested for staining with hematoxylin and eosin (HE), Gomori aldehyde fuchsin (GAF), toluidine blue (TB) and picrosirius red (PSR). Immunohistochemistry was performed to evaluate the levels of α-SMA, CD68 and tryptase. A simple RV remolding model was produced as well by pulmonary artery banding (PAB). RV tissues were collected to determine the degree of MCs infiltration. RESULTS: After MCT challenge, elevated mean pulmonary arterial pressure (mPAP), increased RV systolic pressure (RVSP), pulmonary arterial media hypertrophy as well as distal vascular muscularization gradually occurred with time. MCs recruitment along with CD68+ macrophages accumulation was observed around distal pulmonary vessels and in alveolar septa. Excessive infiltration and degranulation of MCs were detected in MCT-treated group in lung tissues but not in RV. In addition, no exacerbation of MCs infiltration and degranulation in RV was noted in PAB-treated rats, suggesting few contributions of MCs to RV remodeling. CONCLUSIONS: Our findings implied a crucial role of MCs in the remodeling of pulmonary vessels, not RV, which probably through releasing cytokines such as tryptase. The present study enriches the knowledge about PAH, providing a potential profile of MCs as a switch for the treatment of PAH.
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