title: Endothelial insulin-like growth factor-1 modulates proliferation and phenotype of smooth muscle cells induced by low shear stress.
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/cm(2)) was applied and normal shear stress (NSS, 15 dyn/cm(2)) 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.
authors: 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.
authors: Lu
authors: L
authors: Wang
authors: Yue
authors: Y
authors: Han
authors: Yan
authors: Y
authors: Shen
authors: Zhi-Qiang
authors: ZQ
authors: Yan
authors: Ping
authors: P
authors: Zhang
authors: Qing-Ping
authors: QP
authors: Yao
authors: Bao-Rong
authors: BR
authors: Shen
authors: Li-Zhi
authors: LZ
authors: Gao
authors: Ying-Xin
authors: YX
authors: Qi
authors: Zong-Lai
authors: ZL
authors: Jiang
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000235:genetics; D056565:Sirtuin 2 / Q000235:genetics; D013314:Stress, Mechanical
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; C097475:Sirt2 protein, rat; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D056565:Sirtuin 2