title: Effects of high glucose on vascular endothelial growth factor synthesis and secretion in aortic vascular smooth muscle cells from obese and lean Zucker rats.
abstract: Type 1 diabetes is characterized by insulin deficiency, type 2 by both insulin deficiency and insulin resistance: in both conditions, hyperglycaemia is accompanied by an increased cardiovascular risk, due to increased atherosclerotic plaque formation/instabilization and impaired collateral vessel formation. An important factor in these phenomena is the Vascular Endothelial Growth Factor (VEGF), a molecule produced also by Vascular Smooth Muscle Cells (VSMC). We aimed at evaluating the role of high glucose on VEGF-A(164) synthesis and secretion in VSMC from lean insulin-sensitive and obese insulin-resistant Zucker rats (LZR and OZR). In cultured aortic VSMC from LZR and OZR incubated for 24 h with d-glucose (5.5, 15 and 25 mM) or with the osmotic controls l-glucose and mannitol, we measured VEGF-A(164) synthesis (western, blotting) and secretion (western blotting and ELISA). We observed that: (i) d-glucose dose-dependently increases VEGF-A(164) synthesis and secretion in VSMC from LZR and OZR (n = 6, ANOVA p = 0.002-0.0001); (ii) all the effects of 15 and 25 mM d-glucose are attenuated in VSMC from OZR vs. LZR (p = 0.0001); (iii) l-glucose and mannitol reproduce the VEGF-A(164) modulation induced by d-glucose in VSMC from both LZR and OZR. Thus, glucose increases via an osmotic mechanism VEGF synthesis and secretion in VSMC, an effect attenuated in the presence of insulin resistance.
authors.affiliation: Internal Medicine and Metabolic Disease Unit, Department of Clinical and Biological Sciences, San Luigi Gonzaga Faculty of Medicine of the Turin University, San Luigi Gonzaga Hospital, Orbassano (Turin), 10043, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Doronzo
authors.affiliation: Internal Medicine and Metabolic Disease Unit, Department of Clinical and Biological Sciences, San Luigi Gonzaga Faculty of Medicine of the Turin University, San Luigi Gonzaga Hospital, Orbassano (Turin), 10043, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Viretto
authors.affiliation: Internal Medicine and Metabolic Disease Unit, Department of Clinical and Biological Sciences, San Luigi Gonzaga Faculty of Medicine of the Turin University, San Luigi Gonzaga Hospital, Orbassano (Turin), 10043, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Russo
authors.affiliation: Internal Medicine and Metabolic Disease Unit, Department of Clinical and Biological Sciences, San Luigi Gonzaga Faculty of Medicine of the Turin University, San Luigi Gonzaga Hospital, Orbassano (Turin), 10043, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Mattiello
authors.affiliation: Internal Medicine and Metabolic Disease Unit, Department of Clinical and Biological Sciences, San Luigi Gonzaga Faculty of Medicine of the Turin University, San Luigi Gonzaga Hospital, Orbassano (Turin), 10043, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Anfossi
authors.affiliation: Internal Medicine and Metabolic Disease Unit, Department of Clinical and Biological Sciences, San Luigi Gonzaga Faculty of Medicine of the Turin University, San Luigi Gonzaga Hospital, Orbassano (Turin), 10043, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: Trovati
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000494:pharmacology*; D006943:Hyperglycemia / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009997:Osmotic Pressure; D051381:Rats; D011924:Rats, Zucker; D013549:Sweetening Agents / Q000494:pharmacology; D013851:Thinness / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013549:Sweetening Agents; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D005947:Glucose