Abstract
Ganoderic acid A (GAA) is one of the most abundant triterpenoids in Ganoderma lucidum and has protective effect on several vascular diseases. However, the effect of GAA on pulmonary arterial hypertension (PAH) has not been reported. The aim of this study was to investigate the effect of the GAA on the hypoxia-induced phenotypic modulation of PASMCs and the involved transduction pathway. Primary rat pulmonary artery smooth muscle cells (PASMCs) were isolated and cultured under hypoxia condition to induce phenotypic modulation. Our results showed that hypoxia significantly increased the proliferation and migration of PASMCs, as well as inhibited the apoptosis of PASMCs, which were blocked by GAA treatment. In addition, hypoxia-induced dedifferentiation of PASMCs was prevented by GAA with increased the expression levels of myocardin and calponin, and decreased the expression of osteopontin (OPN). Furthermore, GAA suppressed the hypoxia-induced expression of p-PI3K and p-Akt in PASMCs. Treatment with IGF-1 reversed the effects of GAA on proliferation, migration, apoptosis and dedifferentiation in hypoxia-treated PASMCs. Taken together, these findings demonstrated that GAA suppresses the phenotypic modulation of PASMCs through the inactivation of PI3K/Akt pathway. Thus, GAA may be a potent therapeutic agent for PAH in future clinical practice.
Highlights
Pulmonary arterial hypertension (PAH) is a progressive vascular disease with an estimated prevalence of 15 cases per million (Awdish & Cajigas, 2016)
4 Discussion In the current study, we investigated the effect of Ganoderic acid A (GAA) on pulmonary artery smooth muscle cells (PASMCs) in response to hypoxia and uncovered the involved transduction pathway
Our results showed that hypoxia caused significant increases in the cell proliferation, migration and a decrease in cell apoptosis, which were blocked by GAA treatment
Summary
Pulmonary arterial hypertension (PAH) is a progressive vascular disease with an estimated prevalence of 15 cases per million (Awdish & Cajigas, 2016). An improved understanding of the pathophysiology of PAH has revealed that sustained vasoconstriction, abnormal progressive fixed vascular remodeling, accompanied by endothelial dysfunction and activation of fibroblasts and smooth muscle cells are involved in the pathogenesis of PAH (Lan et al, 2018; Montani et al, 2014). Biomedical advances over the last decade have identified the central role of proliferative pulmonary arterial smooth muscle cells (PASMCs) in the development of PAH (He et al, 2020; Hu et al, 2015). It is increasingly believed that prolonged exposure to hypoxia at high altitude leads to PAH development through affecting the phenotype of PASMCs (Veith et al, 2016)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
