title: Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle via Rho/Protein Kinase C and Actin Polymerization.
abstract: Both type 1 and type 2 diabetes are associated with increased risk of cardiovascular disease. This is in part attributed to the effects of hyperglycemia on vascular endothelial and smooth muscle cells, but the underlying mechanisms are not fully understood. In diabetic animal models, hyperglycemia results in hypercontractility of vascular smooth muscle possibly due to increased activation of Rho-kinase. The aim of the present study was to investigate the regulation of contractile smooth muscle markers by glucose and to determine the signaling pathways that are activated by hyperglycemia in smooth muscle cells. Microarray, quantitative PCR, and Western blot analyses revealed that both mRNA and protein expression of contractile smooth muscle markers were increased in isolated smooth muscle cells cultured under high compared with low glucose conditions. This effect was also observed in hyperglycemic Akita mice and in diabetic patients. Elevated glucose activated the protein kinase C and Rho/Rho-kinase signaling pathways and stimulated actin polymerization. Glucose-induced expression of contractile smooth muscle markers in cultured cells could be partially or completely repressed by inhibitors of advanced glycation end products, L-type calcium channels, protein kinase C, Rho-kinase, actin polymerization, and myocardin-related transcription factors. Furthermore, genetic ablation of the miR-143/145 cluster prevented the effects of glucose on smooth muscle marker expression. In conclusion, these data demonstrate a possible link between hyperglycemia and vascular disease states associated with smooth muscle contractility.
authors.affiliation: From the Departments of Experimental Medical Sciences and.
authors.forename: Tran Thi
authors.initials: TT
authors.lastname: Hien
authors.affiliation: From the Departments of Experimental Medical Sciences and.
authors.forename: Karolina M
authors.initials: KM
authors.lastname: Turczyńska
authors.affiliation: From the Departments of Experimental Medical Sciences and.
authors.forename: Diana
authors.initials: D
authors.lastname: Dahan
authors.affiliation: From the Departments of Experimental Medical Sciences and.
authors.forename: Mari
authors.initials: M
authors.lastname: Ekman
authors.affiliation: From the Departments of Experimental Medical Sciences and.
authors.forename: Mario
authors.initials: M
authors.lastname: Grossi
authors.affiliation: Clinical Sciences, Lund University, BMC D12, SE-221 84 Lund, Sweden and.
authors.forename: Johan
authors.initials: J
authors.lastname: Sjögren
authors.affiliation: Clinical Sciences, Lund University, BMC D12, SE-221 84 Lund, Sweden and.
authors.forename: Johan
authors.initials: J
authors.lastname: Nilsson
authors.affiliation: the Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany, and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
authors.affiliation: the Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany, and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Boettger
authors.affiliation: the Department of Clinical Sciences in Malmö, Lund University, 205 02 Malmö, Sweden.
authors.forename: Eliana
authors.initials: E
authors.lastname: Garcia-Vaz
authors.affiliation: From the Departments of Experimental Medical Sciences and.
authors.forename: Karin
authors.initials: K
authors.lastname: Stenkula
authors.affiliation: From the Departments of Experimental Medical Sciences and.
authors.forename: Karl
authors.initials: K
authors.lastname: Swärd
authors.affiliation: the Department of Clinical Sciences in Malmö, Lund University, 205 02 Malmö, Sweden.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Gomez
authors.affiliation: From the Departments of Experimental Medical Sciences and sebastian.albinsson@med.lu.se.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Albinsson
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D003285:Contractile Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003925:Diabetic Angiopathies / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000819:agonists / Q000378:metabolism; D054460:rho-Associated Kinases / Q000737:chemistry / Q000378:metabolism
chemical_list: D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; C543499:MIRN145a microRNA, mouse; D035683:MicroRNAs; C532884:MIRN143 microRNA, mouse; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D020741:rho GTP-Binding Proteins
keywords: Rho (Rho GTPase); actin polymerization; cell differentiation; diabetes; glucose; microRNA (miRNA); vascular smooth muscle cells