PPAR Agonists and Cardiovascular Disease in Diabetes
Peroxisome proliferators activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce card...
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| Format: | Article |
| Language: | English |
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Wiley
2008-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2008/245410 |
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| author | Anna C. Calkin Merlin C. Thomas |
| author_facet | Anna C. Calkin Merlin C. Thomas |
| author_sort | Anna C. Calkin |
| collection | DOAJ |
| description | Peroxisome proliferators activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce cardiovascular risk. However, data from murine models suggests that PPAR agonists also have independent anti-atherosclerotic actions, including the suppression of vascular inflammation, oxidative stress, and activation of the renin angiotensin system. Many of these potentially anti-atherosclerotic effects are thought to be mediated by transrepression of nuclear factor-kB, STAT, and activator protein-1 dependent pathways. In recent clinical trials, PPAR𝛼 agonists have been shown to be effective in the primary prevention of cardiovascular events, while their cardiovascular benefit in patients with established cardiovascular disease remains equivocal. However, the use of
PPAR𝛾 agonists, and more recently dual PPAR𝛼/𝛾 coagonists, has been associated with an excess in cardiovascular events,
possibly reflecting unrecognised fluid retention with potent agonists of the
PPAR𝛾 receptor. Newer pan agonists, which retain their anti-atherosclerotic activity without weight gain, may provide one solution to this problem. However, the complex biologic effects of the PPARs may mean that only vascular targeted agents or pure transrepressors will realise the goal of preventing atherosclerotic vascular disease. |
| format | Article |
| id | doaj-art-b3ed394cdd08483e98cf2dffa267e299 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2008-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-b3ed394cdd08483e98cf2dffa267e2992025-02-03T06:44:34ZengWileyPPAR Research1687-47571687-47652008-01-01200810.1155/2008/245410245410PPAR Agonists and Cardiovascular Disease in DiabetesAnna C. Calkin0Merlin C. Thomas1JDRF Center for Diabetes Complications, Baker Heart Research Institute, Melbourne, VIC 3004, AustraliaJDRF Center for Diabetes Complications, Baker Heart Research Institute, Melbourne, VIC 3004, AustraliaPeroxisome proliferators activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce cardiovascular risk. However, data from murine models suggests that PPAR agonists also have independent anti-atherosclerotic actions, including the suppression of vascular inflammation, oxidative stress, and activation of the renin angiotensin system. Many of these potentially anti-atherosclerotic effects are thought to be mediated by transrepression of nuclear factor-kB, STAT, and activator protein-1 dependent pathways. In recent clinical trials, PPAR𝛼 agonists have been shown to be effective in the primary prevention of cardiovascular events, while their cardiovascular benefit in patients with established cardiovascular disease remains equivocal. However, the use of PPAR𝛾 agonists, and more recently dual PPAR𝛼/𝛾 coagonists, has been associated with an excess in cardiovascular events, possibly reflecting unrecognised fluid retention with potent agonists of the PPAR𝛾 receptor. Newer pan agonists, which retain their anti-atherosclerotic activity without weight gain, may provide one solution to this problem. However, the complex biologic effects of the PPARs may mean that only vascular targeted agents or pure transrepressors will realise the goal of preventing atherosclerotic vascular disease.http://dx.doi.org/10.1155/2008/245410 |
| spellingShingle | Anna C. Calkin Merlin C. Thomas PPAR Agonists and Cardiovascular Disease in Diabetes PPAR Research |
| title | PPAR Agonists and Cardiovascular Disease in Diabetes |
| title_full | PPAR Agonists and Cardiovascular Disease in Diabetes |
| title_fullStr | PPAR Agonists and Cardiovascular Disease in Diabetes |
| title_full_unstemmed | PPAR Agonists and Cardiovascular Disease in Diabetes |
| title_short | PPAR Agonists and Cardiovascular Disease in Diabetes |
| title_sort | ppar agonists and cardiovascular disease in diabetes |
| url | http://dx.doi.org/10.1155/2008/245410 |
| work_keys_str_mv | AT annaccalkin pparagonistsandcardiovasculardiseaseindiabetes AT merlincthomas pparagonistsandcardiovasculardiseaseindiabetes |