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Endothelial Insulin-Like Growth Factor-1 Modulates Proliferation and Phenotype of Smooth Muscle Cells Induced by Low Shear Stress

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Abstract

Endothelial cells (ECs) are directly exposed to shear stress and modulate the neighboring vascular smooth muscle cells (VSMCs), which plays important roles in vascular remodeling during atherosclerosis. Our previous research revealed that insulin-like growth factors (IGFs) might participate in low shear stress (LowSS) induced vascular remodeling, which remains to be elucidated. Using EC/VSMC co-cultured parallel-plate flow chamber, LowSS (5 dyn/cm2) was applied and normal shear stress (NSS, 15 dyn/cm2) was used as control. LowSS induced IGF-1 secretion from ECs, which subsequently phosphorylated IGF-1 receptor (IGF-1R) on co-cultured VSMCs, then increased Akt phosphorylation and Sirt2 expression. Decreasing IGF-1 in ECs by RNA interference (RNAi) reversed these effects on VSMCs. Exogenous IGF-1 increased IGF-1R and Akt phosphorylation, Sirt2 expression, and proliferation of VSMCs, and induced VSMCs towards synthetic phenotype. PI3 K/Akt specific inhibitor wortmannin decreased Sirt2 expression, proliferation, and synthetic phenotype transformation of VSMCs, but had no effect on IGF-1R. Sirt2 RNAi repressed VSMC proliferation and phenotypic transformation, but had no effect on IGF-1R and Akt. Taken together, LowSS induces the secretion of IGF-1 from ECs, which subsequently paracrine influences the co-cultured VSMCs via IGF-1R and Akt phosphorylation, and Sirt2 expression, then results in the proliferation and synthetic phenotype transformation.

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Acknowledgments

This research was supported by the National Natural Science Foundation of China, Nos. 11002091, 11232010 and 11172178, and Shanghai Rising-Star Program, No. 11QA1403200.

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Authors and Affiliations

  1. Institute of Mechanobiology and Medical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang, P.O. Box 888, Shanghai, 200240, China

    Lu Wang, Yue Han, Yan Shen, Zhi-Qiang Yan, Ping Zhang, Qing-Ping Yao, Bao-Rong Shen, Li-Zhi Gao, Ying-Xin Qi & Zong-Lai Jiang

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  1. Lu Wang
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Correspondence to Ying-Xin Qi.

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Associate Editor Cheng Dong oversaw the review of this article.

Lu Wang and Yue Han contributed equally to this work.

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Wang, L., Han, Y., Shen, Y. et al. Endothelial Insulin-Like Growth Factor-1 Modulates Proliferation and Phenotype of Smooth Muscle Cells Induced by Low Shear Stress. Ann Biomed Eng 42, 776–786 (2014). https://doi.org/10.1007/s10439-013-0957-5

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