title: Differential regulation of human aortic smooth muscle cell proliferation by monocyte-derived macrophages from diabetic patients.
abstract: Macrophage accumulation in the arterial wall and smooth muscle cell (SMC) proliferation are features of type 2 diabetes mellitus (DM) and its vascular complications. However, the effects of diabetic monocyte-derived macrophages on vascular SMC proliferation are not clearly understood. In the present study, we investigated the pro-proliferative effect of macrophages isolated from DM patients on vascular SMCs. Macrophage-conditioned media (MCM) were prepared from macrophages isolated from DM patients. DM-MCM treatment induced HASMC proliferation, decreased p21(Cip1) and p27(Kip1) expressions, and increased microRNA (miR)-17-5p and miR-221 expressions. Inhibition of either miR-17-5p or miR-221 inhibited DM-MCM-induced cell proliferation. Inhibition of miR-17-5p abolished DM-MCM-induced p21(Cip1) down-regulation; and inhibition of miR-221 attenuated the DM-MCM-induced p27(Kip1) down-regulation. Furthermore, blocking assays demonstrated that PDGF-CC in DM-MCM is the major mediators of cell proliferation in SMCs. In conclusion, our present data support the hypothesis that SMC proliferation stimulated by macrophages may play critical roles in vascular complications in DM patients and suggest a new mechanism by which arterial disease is accelerated in diabetes.
authors.affiliation: Division of Nephrology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Te-Chuan
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Department of Cardiology, St. Martin De Porres Hospital, Chiayi, Taiwan.
authors.forename: Mao-Ling
authors.initials: ML
authors.lastname: Sung
authors.affiliation: Institute of Nursing and Department of Nursing, Chang Gung University of Science and Technology, Chronic Diseases and Health Promotion Research Center, CGUST, Taoyuan, Taiwan; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
authors.forename: Hsing-Chun
authors.initials: HC
authors.lastname: Kuo
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Shao-Ju
authors.initials: SJ
authors.lastname: Chien
authors.affiliation: Department of Cardiology, St. Martin De Porres Hospital, Chiayi, Taiwan.
authors.forename: Chia-Kuang
authors.initials: CK
authors.lastname: Yen
authors.affiliation: Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan.
authors.forename: Cheng-Nan
authors.initials: CN
authors.lastname: Chen
mesh_terms: D000328:Adult; D001011:Aorta / Q000166:cytology*; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008222:Lymphokines / Q000032:analysis; D008264:Macrophages / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D020574:Proto-Oncogene Proteins c-sis / Q000032:analysis
chemical_list: D000077214:Becaplermin; D017077:Culture Media, Conditioned; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008222:Lymphokines; D035683:MicroRNAs; D053495:Osteopontin; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C524941:MIRN17 microRNA, human; C525709:MIR221, human; C411423:platelet-derived growth factor C