title: A crosstalk triggered by hypoxia and maintained by MCP-1/miR-98/IL-6/p38 regulatory loop between human aortic smooth muscle cells and macrophages leads to aortic smooth muscle cells apoptosis via Stat1 activation.
abstract: Hypoxia and inflammation are central characteristics of the abdominal aortic aneurysm (AAA), but the mechanisms for their relationship and actual role remain far from full understood. Here, we showed MCP-1 (monocyte chemotactic protein-1) induced by hypoxia in primary human Aortic Smooth Muscle Cells (hASMCs) increased the chemotaxis of THP-1 macrophages and MCP-1 induced IL-6 expression in THP-1 cells via downregulating miR-98 which directly targets IL-6. In addition, IL-6 positively feedback regulated MCP-1 expression in hASMCs via p38 signal that is independent on hypoxia, and inhibition of p38 signal blocked the effect of IL-6 on MCP-1 expression regulation. Moreover, IL-6 exposure time-dependently induces phASMCs apoptosis via Stat1 activation. Collectively, our data provide compelling evidence on the association between hypoxia and inflammation triggered by hypoxia and then mediated by MCP-1/miR-98/IL-6/p38 regulatory loop, which leads to hASMCs apoptosis via Stat1 activation to contribute to AAA formation and progression.
authors.affiliation: Department of Vascular Surgery, The 2nd Xiangya Hospital, Central South University 139 Renmin Middle Road, Changsha 410011, Hunan, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Vascular Surgery, The 2nd Xiangya Hospital, Central South University 139 Renmin Middle Road, Changsha 410011, Hunan, People's Republic of China.
authors.forename: Chang
authors.initials: C
authors.lastname: Shu
authors.affiliation: Hunan Tumor Hospital Changsha, Hunan, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Vascular Surgery, The 2nd Xiangya Hospital, Central South University 139 Renmin Middle Road, Changsha 410011, Hunan, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
mesh_terms: D001011:Aorta / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D015687:Cell Hypoxia; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D020239:Receptor Cross-Talk / Q000502:physiology; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D014162:Transfection
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; C508600:IL6 protein, human; D015850:Interleukin-6; C546084:MIRN98 microRNA, human; D035683:MicroRNAs; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human
keywords: Abdominal aortic aneurysm; IL-6; MCP-1; hypoxia; macrophage