title: Metabolic control analysis of the Warburg-effect in proliferating vascular smooth muscle cells.
abstract: The accumulation and proliferation of vascular smooth muscle cells (VSMC) within the vessel wall is an important pathogenic feature in the development of atherosclerosis. Glucose metabolism has been implicated to play an important role in this cellular mechanism. To further elucidate the role of glucose metabolism in atherogenesis, glycolysis and its regulation have been investigated in proliferating VSMC. Platelet derived growth factor (PDGF BB)-induced proliferation of VSMCs significantly stimulated glucose flux through glycolysis. Further evaluating the enzymatic regulation of this pathway, the analysis of flux:metabolite co-responses revealed that anaerobic glycolytic flux is controlled at different sites of gycolysis in proliferating VSMCs, being consistent with the concept of multisite modulation. These findings indicate that regulation of glycolytic flux in proliferating VSMCs differs from traditional concepts of metabolic control of the Embden-Meyerhof pathway.
authors.affiliation: Innere Medizin III, Universität Heidelberg, Heidelberg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Werle
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuzer
authors.forename: Julia
authors.initials: J
authors.lastname: Höfele
authors.forename: Albrecht
authors.initials: A
authors.lastname: Elsässer
authors.forename: Cordula
authors.initials: C
authors.lastname: Ackermann
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Achim M
authors.initials: AM
authors.lastname: Vogt
mesh_terms: D000077214:Becaplermin; D049109:Cell Proliferation; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D020574:Proto-Oncogene Proteins c-sis
chemical_list: D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D005947:Glucose