Cardiac Peroxisome Proliferator-activated Receptors Expressions in Hypertension Coexisting with Diabetes.
Summary of "Cardiac Peroxisome Proliferator-activated Receptors Expressions in Hypertension Coexisting with Diabetes."
Hypertension and diabetes mellitus (DM) are common chronic disorders that often coexist. DM and peroxisome proliferator-activated receptors (PPAR)-gamma agonists may directly impair heart functions. However, the effects of DM and PPAR-g agonists on hypertensive myocardium are not known. Hence, the objective of this study was to investigate whether DM and a PPAR-gamma agonist (rosiglitazone, RGZ) can modulate the effects of hypertension on myocardial expressions of PPAR isoforms. Cardiac PPAR isoforms, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 were evaluated by real-time PCR and Western blotting in spontaneously hypertensive rat (SHR), diabetic SHR, diabetic SHR treated with RGZ (5 mg/kg), and Wistar-Kyota control rats. Cardiac nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase activity was quantified by superoxide dismutase (SOD)-sensitive cytochrome c reduction assay. As compared to control hearts, SHR hearts had decreased mRNA and protein levels by 39% and 44% in PPAR-alpha and by 37% and 42% in PPAR-delta, but had increased by 1.9- and 1.4-fold in PPAR-gamma, respectively. The SHR-induced changes in mRNA and protein of cardiac PPAR isoforms were enhanced in diabetic SHR, which were attenuated in diabetic SHR treated with RGZ. Cardiac TNF-alpha, IL-6 protein, and NAD(P)H oxidase activities were increased in SHR and were further aggravated in diabetic SHR. RGZ treatment decreased TNF-alpha, IL-6 protein, and NAD(P)H oxidase activities in diabetic SHR hearts. These findings suggest that DM and PPAR-gamma agonist modulated the hypertensive effects on cardiac PPAR isoform expressions.
Affiliation
Journal Details
This article was published in the following journal.
Name: Clinical science (London, England : 1979)
ISSN: 1470-8736
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21501116
- DOI: http://dx.doi.org/10.1042/CS20100529
Medical and Biotech [MESH] Definitions
Peroxisome Proliferator-activated Receptors
TRANSCRIPTION FACTORS that are activated by ligands and heterodimerize with RETINOID X RECEPTORS and bind to peroxisome proliferator response elements in the promoter regions of target genes.
Mediator Complex Subunit 1
A mediator complex subunit that is believed to play a key role in the coactivation of nuclear receptor-activated transcription by the mediator complex. It interacts with a variety of nuclear receptors including RETINOIC ACID RECEPTORS; THYROID HORMONE RECEPTORS; VITAMIN D RECEPTORS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; ESTROGEN RECEPTORS; and GLUCOCORTICOID RECEPTORS.
Thiazolidinediones
THIAZOLES with two keto oxygens. Members are insulin-sensitizing agents which overcome INSULIN RESISTANCE by activation of the peroxisome proliferator activated receptor gamma (PPAR-gamma).
Nafenopin
A peroxisome proliferator that is used experimentally to promote liver tumors. It has been used as an antihyperlipoproteinemic agent.
Receptors, Proteinase-activated
A class of receptors that are activated by the action of PROTEINASES. The most notable examples are the THROMBIN RECEPTORS. The receptors contain cryptic ligands that are exposed upon the selective proteolysis of specific N-terminal cleavage sites.
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