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Apelin suppresses apoptosis of human vascular smooth muscle cells via APJ/PI3-K/Akt signaling pathways

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Abstract

Apoptosis of vascular smooth muscle cells (VSMCs) plays an important role in regulating vascular remodeling during cardiovascular diseases. Apelin is the endogenous ligand for the G-protein-coupled receptor APJ and plays an important role in the cardiovascular system. However, the mechanisms of apelin on apoptosis of VSMCs have not been elucidated. Using a culture of human VSMCs as a model for the study of apoptosis, the relationship between apelin and apoptosis of human VSMCs and the signal pathway involved were investigated. Using western blotting, we confirmed that VSMCs could express APJ. To evaluate the possible role of apelin in VSMC apoptosis, we assessed its effect on apoptosis of human VSMCs. The results showed that apelin inhibited human VSMCs apoptosis induced by serum deprivation. Suppression of APJ with small-interfering RNA (siRNA) abolished the anti-apoptotic activity of apelin. Apelin increased Bcl-2 protein expression, but decreased Bax protein expression. An increase in activation of extracellular signal-regulated protein kinase (ERK) and Akt (a downstream effector of phosphatidylinositol 3-kinase) was shown after apelin stimulation. Suppression of APJ with siRNA abolished the apelin-induced activation of ERK and Akt. LY294002 (a PI3-K inhibitor) blocked apelin-induced activation of Akt and abolished the apelin-induced antiapoptotic activity. Our study suggests that apelin suppresses serum deprivation-induced apoptosis of human VSMCs, and that the anti-apoptotic action is mediated through the APJ/PI3-K/Akt signaling pathways.

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Acknowledgments

This work was supported by funding from The National Natural Science Foundation of China (No. 30801174 and 30900622), the Ph. D. Programs Foundation of Ministry of Education of China (No.200805331017), and clinic medicine special research fund-endocrinology disease research fund (10020040226).

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Authors and Affiliations

  1. Department of Pediatrics, The Second Xiang-Ya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China

    Rong-Rong Cui, Ding-An Mao, Cheng Wang & Xing-Xing Zhang

  2. Department of Urology, The Second Xiang-Ya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China

    Lu Yi

  3. Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, #139 Middle Renmin Road, Changsha, 410011, Hunan, People’s Republic of China

    Rong-Rong Cui, Hui Xie, Xian-Ping Wu, Hua Zhou, Ji-Cai Meng, Ling-Qing Yuan & Er-Yuan Liao

  4. Department of Cardiothoracic Surgery, The Second Xiang-Ya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China

    Xiao-Bo Liao

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  1. Rong-Rong Cui
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  2. Ding-An Mao
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Correspondence to Ling-Qing Yuan or Er-Yuan Liao.

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Rong-Rong Cui, Ding-An Mao and Lu Yi contributed equally to this work.

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Cui, RR., Mao, DA., Yi, L. et al. Apelin suppresses apoptosis of human vascular smooth muscle cells via APJ/PI3-K/Akt signaling pathways. Amino Acids 39, 1193–1200 (2010). https://doi.org/10.1007/s00726-010-0555-x

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