The protective effect of rosuvastatin in human umbilical endothelial cells exposed to constant or intermittent high glucose

Ludovica Piconi, Maddalena Corgnali, Roberto Da Ros, Roberta Assaloni, Teodoro Piliego, Antonio Ceriello

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

In diabetes the exposure of the vascular endothelium to high glucose levels results in increased oxidative insult and in vascular dysfunction. We have investigated the effects of rosuvastatin on oxidative stress and apoptosis induced in human umbilical vein endothelial cells (HUVECs) by constant and intermittent high glucose levels. HUVECs were incubated for 14 days in either low (5 mM) or high (20 mM) glucose concentrations, or intermittent high and low glucose on a daily basis. Constant high glucose levels increased p47-phox, p67-phox, and p22-phox expression [components of the Nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase complex]; endothelial nitric oxide synthase, nitric oxide, and O2- production; nitrotyrosine, 8-hydroxy-2′-deoxyguanosine, and caspase-3 expression; and reduced Bcl-2 expression. These effects were significantly greater under intermittent compared to constant high/low glucose conditions. The effect of rosuvastatin (1 μM) in the presence or absence of mevalonate (200 μM) was evaluated in the cells under both constant and intermittent glucose conditions. Rosuvastatin almost normalized all these parameters. These effects of rosuvastatin were prevented when mevalonate was also added, demonstrating the link to inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase. These data suggest that rosuvastatin has the potential to prevent damage to and apoptosis of HUVECs induced by high glucose exposure, by reducing oxidative stress. The action of rosuvastatin on antioxidant pathways is related to the inhibition of the overexpression of components of NAD(P)H oxidase induced by the two conditions of high glucose.

Original languageEnglish
Pages (from-to)38-45
Number of pages8
JournalJournal of Diabetes and its Complications
Volume22
Issue number1
DOIs
Publication statusPublished - Jan 2008

Fingerprint

Umbilicus
Endothelial Cells
Glucose
Human Umbilical Vein Endothelial Cells
Mevalonic Acid
Oxidoreductases
NADP
Oxidative Stress
Apoptosis
Rosuvastatin Calcium
Nitric Oxide Synthase Type III
Vascular Endothelium
Caspase 3
Blood Vessels
Nitric Oxide
Antioxidants

Keywords

  • HUVECs
  • Intermittent glucose
  • Oxidative stress
  • Rosuvastatin

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

The protective effect of rosuvastatin in human umbilical endothelial cells exposed to constant or intermittent high glucose. / Piconi, Ludovica; Corgnali, Maddalena; Da Ros, Roberto; Assaloni, Roberta; Piliego, Teodoro; Ceriello, Antonio.

In: Journal of Diabetes and its Complications, Vol. 22, No. 1, 01.2008, p. 38-45.

Research output: Contribution to journalArticle

Piconi, Ludovica ; Corgnali, Maddalena ; Da Ros, Roberto ; Assaloni, Roberta ; Piliego, Teodoro ; Ceriello, Antonio. / The protective effect of rosuvastatin in human umbilical endothelial cells exposed to constant or intermittent high glucose. In: Journal of Diabetes and its Complications. 2008 ; Vol. 22, No. 1. pp. 38-45.
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