Peroxisome proliferator-activated receptor-gamma as a potential therapeutic target in the treatment of preeclampsia.

Hdl Handle:
http://hdl.handle.net/10147/205806
Title:
Peroxisome proliferator-activated receptor-gamma as a potential therapeutic target in the treatment of preeclampsia.
Authors:
McCarthy, Fergus P; Drewlo, Sascha; Kingdom, John; Johns, Edward J; Walsh, Sarah K; Kenny, Louise C
Affiliation:
Anu Research Centre, University College Cork, Cork University Maternity Hospital,, Wilton, Cork, Ireland. fergusmccarthy@gmail.com
Citation:
Hypertension. 2011 Aug;58(2):280-6. Epub 2011 Jun 20.
Journal:
Hypertension
Issue Date:
31-Jan-2012
URI:
http://hdl.handle.net/10147/205806
DOI:
10.1161/HYPERTENSIONAHA.111.172627
PubMed ID:
21690483
Abstract:
Preeclampsia is a multisystemic disorder of pregnancy characterized by hypertension, proteinuria, and maternal endothelial dysfunction. It is a major cause of maternal and perinatal morbidity and mortality and is thought to be attributable, in part, to inadequate trophoblast invasion. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor expressed in trophoblasts, and the vasculature of which activation has been shown to improve endothelium-dependent vasodilatation in hypertensive conditions. We investigated the effects of the administration of a PPAR-gamma agonist using the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. The selective PPAR-gamma agonist, rosiglitazone, was administered to pregnant rats that had undergone RUPP surgery. To investigate whether any observed beneficial effects of PPAR-gamma activation were mediated by the antioxidant enzyme, heme oxygenase 1, rosiglitazone was administered in combination with the heme oxygenase 1 inhibitor tin-protoporphyrin IX. RUPP rats were characterized by hypertension, endothelial dysfunction, and elevated microalbumin:creatinine ratios. Rosiglitazone administration ameliorated hypertension, improved vascular function, and reduced the elevated microalbumin:creatinine ratio in RUPP rats. With the exception of microalbumin:creatinine ratio, these beneficial effects were abrogated in the presence of the heme oxygenase 1 inhibitor. Administration of a PPAR-gamma agonist prevented the development of several of the pathophysiological characteristics associated with the RUPP model of preeclampsia, via a heme oxygenase 1-dependent pathway. The findings from this study provide further insight into the underlying etiology of preeclampsia and a potential therapeutic target for the treatment of preeclampsia.
Language:
eng
MeSH:
Animals; Blood Pressure/*drug effects; Female; Metalloporphyrins/*pharmacology; PPAR gamma/agonists/*metabolism; Pre-Eclampsia/*metabolism/physiopathology; Pregnancy; Protoporphyrins/*pharmacology; Rats; Rats, Sprague-Dawley; Thiazolidinediones/*pharmacology
ISSN:
1524-4563 (Electronic); 0194-911X (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorMcCarthy, Fergus Pen_GB
dc.contributor.authorDrewlo, Saschaen_GB
dc.contributor.authorKingdom, Johnen_GB
dc.contributor.authorJohns, Edward Jen_GB
dc.contributor.authorWalsh, Sarah Ken_GB
dc.contributor.authorKenny, Louise Cen_GB
dc.date.accessioned2012-01-31T16:42:55Z-
dc.date.available2012-01-31T16:42:55Z-
dc.date.issued2012-01-31T16:42:55Z-
dc.identifier.citationHypertension. 2011 Aug;58(2):280-6. Epub 2011 Jun 20.en_GB
dc.identifier.issn1524-4563 (Electronic)en_GB
dc.identifier.issn0194-911X (Linking)en_GB
dc.identifier.pmid21690483en_GB
dc.identifier.doi10.1161/HYPERTENSIONAHA.111.172627en_GB
dc.identifier.urihttp://hdl.handle.net/10147/205806-
dc.description.abstractPreeclampsia is a multisystemic disorder of pregnancy characterized by hypertension, proteinuria, and maternal endothelial dysfunction. It is a major cause of maternal and perinatal morbidity and mortality and is thought to be attributable, in part, to inadequate trophoblast invasion. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor expressed in trophoblasts, and the vasculature of which activation has been shown to improve endothelium-dependent vasodilatation in hypertensive conditions. We investigated the effects of the administration of a PPAR-gamma agonist using the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. The selective PPAR-gamma agonist, rosiglitazone, was administered to pregnant rats that had undergone RUPP surgery. To investigate whether any observed beneficial effects of PPAR-gamma activation were mediated by the antioxidant enzyme, heme oxygenase 1, rosiglitazone was administered in combination with the heme oxygenase 1 inhibitor tin-protoporphyrin IX. RUPP rats were characterized by hypertension, endothelial dysfunction, and elevated microalbumin:creatinine ratios. Rosiglitazone administration ameliorated hypertension, improved vascular function, and reduced the elevated microalbumin:creatinine ratio in RUPP rats. With the exception of microalbumin:creatinine ratio, these beneficial effects were abrogated in the presence of the heme oxygenase 1 inhibitor. Administration of a PPAR-gamma agonist prevented the development of several of the pathophysiological characteristics associated with the RUPP model of preeclampsia, via a heme oxygenase 1-dependent pathway. The findings from this study provide further insight into the underlying etiology of preeclampsia and a potential therapeutic target for the treatment of preeclampsia.en_GB
dc.language.isoengen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshBlood Pressure/*drug effectsen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshMetalloporphyrins/*pharmacologyen_GB
dc.subject.meshPPAR gamma/agonists/*metabolismen_GB
dc.subject.meshPre-Eclampsia/*metabolism/physiopathologyen_GB
dc.subject.meshPregnancyen_GB
dc.subject.meshProtoporphyrins/*pharmacologyen_GB
dc.subject.meshRatsen_GB
dc.subject.meshRats, Sprague-Dawleyen_GB
dc.subject.meshThiazolidinediones/*pharmacologyen_GB
dc.titlePeroxisome proliferator-activated receptor-gamma as a potential therapeutic target in the treatment of preeclampsia.en_GB
dc.contributor.departmentAnu Research Centre, University College Cork, Cork University Maternity Hospital,, Wilton, Cork, Ireland. fergusmccarthy@gmail.comen_GB
dc.identifier.journalHypertensionen_GB
dc.description.provinceMunster-
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