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 language | English |
|---|---|
| Pages (from-to) | 38-45 |
| Number of pages | 8 |
| Journal | Journal of Diabetes and its Complications |
| Volume | 22 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2008 |
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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 journal › Article
}
TY - JOUR
T1 - The protective effect of rosuvastatin in human umbilical endothelial cells exposed to constant or intermittent high glucose
AU - Piconi, Ludovica
AU - Corgnali, Maddalena
AU - Da Ros, Roberto
AU - Assaloni, Roberta
AU - Piliego, Teodoro
AU - Ceriello, Antonio
PY - 2008/1
Y1 - 2008/1
N2 - 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.
AB - 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.
KW - HUVECs
KW - Intermittent glucose
KW - Oxidative stress
KW - Rosuvastatin
UR - http://www.scopus.com/inward/record.url?scp=37749030539&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=37749030539&partnerID=8YFLogxK
U2 - 10.1016/j.jdiacomp.2007.03.004
DO - 10.1016/j.jdiacomp.2007.03.004
M3 - Article
VL - 22
SP - 38
EP - 45
JO - Journal of Diabetes and its Complications
JF - Journal of Diabetes and its Complications
SN - 1056-8727
IS - 1
ER -