Phenotype modulation in cultures of vascular smooth muscle cells from diabetic rats: association with increased nitric oxide synthase expression and superoxide anion generation

Andrea Giaccari, Assunta Pandolfi, Alfredo Grilli, Carlo Cilli, Antonia Patruno, Sara Di Silvestre, Maria Anna De Lutiis, Giuliana Pellegrini, Fabio Capani, Agostino Consoli, Mario Felaco

Research output: Contribution to journalArticlepeer-review

50 Citations (SciVal)

Abstract

Proliferative modification of vascular smooth muscle cell (vSMC) and impaired bioavailability of nitric oxide (NO) have both been proposed among the mechanisms linking diabetes and atherosclerosis. However, diabetes induced modifications in phenotype and nitric oxide synthase(s) (NOS) expression and activity in vSMC have not been fully characterized. In this study, cell morphology, proliferative response to serum, alpha-SMactin levels, eNOS expression and activity, cGMP intracellular content, and superoxide anion release were measured in cultures of vSMC obtained from aorta medial layer of ten diabetic (90% pancreatectomy, DR) and ten control (sham surgery, CR) rats. Vascular SMC from DR showed a less evident "hill and valley" culture morphology, increased growth response to serum, greater saturation density, and lower levels of alpha-SMactin. In the same cells, as compared to CR cells, eNOS mRNA levels and NOS activity were increased, while intracellular cGMP level was lower and superoxide anion production was significantly greater. These data indicate that chronic hyperglycemia might induce, in the vascular wall, an increased number of vSMC proliferative clones which persist in culture and are associated with increased eNOS expression and activity. However, upregulation of eNOS and increased NO synthesis occur in the presence of a marked concomitant increase of O(2-) production. Since NO bioavailability, as reflected by cGMP levels, was not increased in DR cells, it is tempting to hypothesize that the proliferative phenotype observed in DR cells is associated with a redox imbalance responsible quenching and/or trapping of NO, with the consequent loss of its biological activity.
Original languageEnglish
Pages (from-to)378-385
Number of pages8
JournalJournal of Cellular Physiology
Volume2003
Publication statusPublished - 2003

Keywords

  • Insulin Resistance
  • diabetes
  • nitric oxide

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