PPARs and diabetes-associated atherosclerosis.

A C Calkin, Karin Jandeleit-Dahm, e sebekova, Terri Jean Allen, Jacques Mizrahi, Mark Emmauel Cooper, Chris Tikellis

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors affecting the regulation of various genes relevant to the pathogenesis of diabetic complications. A number of drugs have been developed to act as agonists of the three PPARs. To date, PPAR isoforms that have been identified are the alpha, beta/delta, and gamma isosforms. Fenofibrate and gemfibrozil are two drugs that act as PPARalpha agonists and are currently in use in the clinical setting. Rosiglitazone is a PPARgamma agonist also in clinical use. These drugs have proved very useful in regulation of either glucose or lipid metabolism and consequently are used in patients with type 2 diabetes. Here, we will review the anti-atherosclerotic potential of PPAR agonists with particular emphasis on recent studies in an animal model of diabetes-associated atherosclerosis, the streptozotocin diabetic apolipoprotein E deficient mouse. These studies have shown both PPARalpha agonists, gemfibrozil and fenofibrate, confer anti-atherosclerotic effects, partly independent of their metabolic effects. Similar positive findings have also been detected in a dose-dependent manner with the PPARgamma agonist, rosiglitazone. The potential clinical implications of these findings are also discussed in view of the recently reported results of the PROACTIVE and FIELD clinical trials with the PPAR agonists rosiglitazone and fenofibrate respectively.
Original languageEnglish
Pages (from-to)2736-41
Number of pages5
JournalCurrent Pharmaceutical Design
Volume13
Issue number26
Publication statusPublished - 2007
Externally publishedYes

Cite this

Calkin, A C ; Jandeleit-Dahm, Karin ; sebekova, e ; Allen, Terri Jean ; Mizrahi, Jacques ; Cooper, Mark Emmauel ; Tikellis, Chris. / PPARs and diabetes-associated atherosclerosis. In: Current Pharmaceutical Design. 2007 ; Vol. 13, No. 26. pp. 2736-41.
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title = "PPARs and diabetes-associated atherosclerosis.",
abstract = "Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors affecting the regulation of various genes relevant to the pathogenesis of diabetic complications. A number of drugs have been developed to act as agonists of the three PPARs. To date, PPAR isoforms that have been identified are the alpha, beta/delta, and gamma isosforms. Fenofibrate and gemfibrozil are two drugs that act as PPARalpha agonists and are currently in use in the clinical setting. Rosiglitazone is a PPARgamma agonist also in clinical use. These drugs have proved very useful in regulation of either glucose or lipid metabolism and consequently are used in patients with type 2 diabetes. Here, we will review the anti-atherosclerotic potential of PPAR agonists with particular emphasis on recent studies in an animal model of diabetes-associated atherosclerosis, the streptozotocin diabetic apolipoprotein E deficient mouse. These studies have shown both PPARalpha agonists, gemfibrozil and fenofibrate, confer anti-atherosclerotic effects, partly independent of their metabolic effects. Similar positive findings have also been detected in a dose-dependent manner with the PPARgamma agonist, rosiglitazone. The potential clinical implications of these findings are also discussed in view of the recently reported results of the PROACTIVE and FIELD clinical trials with the PPAR agonists rosiglitazone and fenofibrate respectively.",
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Calkin, AC, Jandeleit-Dahm, K, sebekova, E, Allen, TJ, Mizrahi, J, Cooper, ME & Tikellis, C 2007, 'PPARs and diabetes-associated atherosclerosis.' Current Pharmaceutical Design, vol. 13, no. 26, pp. 2736-41.

PPARs and diabetes-associated atherosclerosis. / Calkin, A C; Jandeleit-Dahm, Karin; sebekova, e; Allen, Terri Jean; Mizrahi, Jacques; Cooper, Mark Emmauel; Tikellis, Chris.

In: Current Pharmaceutical Design, Vol. 13, No. 26, 2007, p. 2736-41.

Research output: Contribution to journalReview ArticleResearchpeer-review

TY - JOUR

T1 - PPARs and diabetes-associated atherosclerosis.

AU - Calkin, A C

AU - Jandeleit-Dahm, Karin

AU - sebekova, e

AU - Allen, Terri Jean

AU - Mizrahi, Jacques

AU - Cooper, Mark Emmauel

AU - Tikellis, Chris

PY - 2007

Y1 - 2007

N2 - Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors affecting the regulation of various genes relevant to the pathogenesis of diabetic complications. A number of drugs have been developed to act as agonists of the three PPARs. To date, PPAR isoforms that have been identified are the alpha, beta/delta, and gamma isosforms. Fenofibrate and gemfibrozil are two drugs that act as PPARalpha agonists and are currently in use in the clinical setting. Rosiglitazone is a PPARgamma agonist also in clinical use. These drugs have proved very useful in regulation of either glucose or lipid metabolism and consequently are used in patients with type 2 diabetes. Here, we will review the anti-atherosclerotic potential of PPAR agonists with particular emphasis on recent studies in an animal model of diabetes-associated atherosclerosis, the streptozotocin diabetic apolipoprotein E deficient mouse. These studies have shown both PPARalpha agonists, gemfibrozil and fenofibrate, confer anti-atherosclerotic effects, partly independent of their metabolic effects. Similar positive findings have also been detected in a dose-dependent manner with the PPARgamma agonist, rosiglitazone. The potential clinical implications of these findings are also discussed in view of the recently reported results of the PROACTIVE and FIELD clinical trials with the PPAR agonists rosiglitazone and fenofibrate respectively.

AB - Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors affecting the regulation of various genes relevant to the pathogenesis of diabetic complications. A number of drugs have been developed to act as agonists of the three PPARs. To date, PPAR isoforms that have been identified are the alpha, beta/delta, and gamma isosforms. Fenofibrate and gemfibrozil are two drugs that act as PPARalpha agonists and are currently in use in the clinical setting. Rosiglitazone is a PPARgamma agonist also in clinical use. These drugs have proved very useful in regulation of either glucose or lipid metabolism and consequently are used in patients with type 2 diabetes. Here, we will review the anti-atherosclerotic potential of PPAR agonists with particular emphasis on recent studies in an animal model of diabetes-associated atherosclerosis, the streptozotocin diabetic apolipoprotein E deficient mouse. These studies have shown both PPARalpha agonists, gemfibrozil and fenofibrate, confer anti-atherosclerotic effects, partly independent of their metabolic effects. Similar positive findings have also been detected in a dose-dependent manner with the PPARgamma agonist, rosiglitazone. The potential clinical implications of these findings are also discussed in view of the recently reported results of the PROACTIVE and FIELD clinical trials with the PPAR agonists rosiglitazone and fenofibrate respectively.

M3 - Review Article

VL - 13

SP - 2736

EP - 2741

JO - Current Pharmaceutical Design

JF - Current Pharmaceutical Design

SN - 1381-6128

IS - 26

ER -

Calkin AC, Jandeleit-Dahm K, sebekova E, Allen TJ, Mizrahi J, Cooper ME et al. PPARs and diabetes-associated atherosclerosis. Current Pharmaceutical Design. 2007;13(26):2736-41.