Abstract
Apelin is highly expressed in the lungs, especially in the pulmonary vasculature, but the functional role of apelin under pathological conditions is still undefined. Hypoxic pulmonary hypertension is the most common cause of acute right heart failure, which may involve the remodeling of artery and regulation of autophagy. In this study, we determined whether treatment with apelin regulated the proliferation and migration of rat pulmonary arterial smooth muscle cells (SMCs) under hypoxia, and investigated the underlying mechanism and the relationship with autophagy. Our data showed that hypoxia activated autophagy significantly at 24 hrs. The addition of exogenous apelin decreased the level of autophagy and further inhibited pulmonary arterial SMC (PASMC) proliferation via activating downstream phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/the mammalian target of Rapamycin (mTOR) signal pathways. The inhibition of the apelin receptor (APJ) system by siRNA abolished the inhibitory effect of apelin in PASMCs under hypoxia. This study provides the evidence that exogenous apelin treatment contributes to inhibit the proliferation and migration of PASMCs by regulating the level of autophagy.
Highlights
Hypoxic pulmonary hypertension (HPH) is a severe disease characterized by pulmonary vasoconstriction, pulmonary arterial remodeling and abnormal angiogenesis
To mimic the hypoxia-induced proliferation of pulmonary arterial smooth muscle cells (SMCs) in vivo, primary cultured PASMCs were incubated for different times (6, 12, 24 and 48 hrs) at 1% oxygen concentration in the hypoxia chamber with the 21% oxygen of the room air being used for controls
Our data indicate that enhanced transitions from the G1 into the S phase were measured under hypoxic conditions (P < 0.05, Fig. 1C). These results indicate that the proliferation, migration and the cell cycle progression of PASMCs were stimulated by hypoxia treatment
Summary
Hypoxic pulmonary hypertension (HPH) is a severe disease characterized by pulmonary vasoconstriction, pulmonary arterial remodeling and abnormal angiogenesis. Hypoxic pulmonary hypertension eventually leads to right ventricular pressure overload, which is the most common cause of acute right heart failure [1,2,3] Autophagy has been implicated in development and several other human diseases [10], including cancer [11, 12], neurodegenerative diseases [13], inflammatory diseases [14] and cardiovascular diseases [15]. Very little is currently known about the physiological function of autophagy in the clinical progression of human pulmonary diseases.
Sign-in/Register to view highlights & summary 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.
