The Effects of Rosiglitazone and High Glucose on Protein Expression in Endothelial Cells

Abstract

Rosiglitazone is a thiazolidinedione used to treat insulin resistance in diabetes. Although thiazolidinediones may also exert cardiovascular effects, contrasting results were reported. Favorable effects were shown for pioglitazone, whereas adverse reactions were suspected for rosiglitazone. Therefore, a reassessment of the molecular effects of rosiglitazone on vascular cells is required. We tested the effects of rosiglitazone on the proteome of human endothelial cells grown under either normal or high glucose levels. Protein profiles were analyzed in both membrane and cytosolic fractions. About 150 cytosolic proteins, and approximately 100 membrane proteins, were detected. Two-thirds of the proteins significantly altered by high glucose were also modulated by rosiglitazone in an antagonistic way. Half of these proteins are involved in apoptosis. Using an independent assay of apoptosis based on nucleosome quantification, an approximately 20% stimulation by high versus normal glucose was shown (p < 0.05). Conversely, rosiglitazone reduced apoptosis by approximately 30-50% in cells exposed to either glucose conditions (p < 0.001). In addition, rosiglitazone differently modulated cytoskeleton and energy metabolism-related proteins. Our data show novel, potential sites of action of rosiglitazone through protein expression of endothelial cells. These mechanisms may foster new investigations on the overall vascular effects of this compound, and help to discriminate between desired and adverse effects.

Rosiglitazone Attenuates Endothelial Progenitor Cell Apoptosis Induced by TNF-α via ERK/MAPK and NF-κB Signal Pathways

“…Rosiglitazone (RSG), a peroxisome proliferator-activated receptors (PPARs) agonist, has been used in the treatment of type 2 diabetes for a decade and its actions have been convincingly shown to reach far beyond its use as an insulin sensitizer. Pretreatment with rosiglitazone increases survival of endothelial cells and myocardial cells (10,11). In recent years, the effects of rosiglitazone on EPCs have been also studied and it was reported to promote EPC number and migratory activity (12).…”

Protein Sets Define Disease States and Predict In Vivo Effects of Drug Treatment

“…Previous attempts of using mass spectrometry for protein quantification in mammalian disease models were limited to analysis of a small number of usually abundant proteins, which made comprehensive pathway analysis and physiological outcome prediction impossible (5,6). Recent technical pilot studies provided extensive information on the protein inventories of different mouse tissues (7,8), and isotope-labeled mice have been introduced as a resource for accurate protein quantification (9).…”

Proteomic differences in brain vessels of Alzheimer’s disease mice: Normalization by PPARγ agonist pioglitazone

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