Cardiac peroxisome-proliferator-activated receptor expression in hypertension co-existing with diabetes

Abstract

Hypertension and DM (diabetes mellitus) are common chronic disorders that often co-exist. DM and PPAR (peroxisome-proliferator-activated receptor)-γ agonists may directly impair heart function. However, the effects of DM and PPAR-γ agonists on hypertensive myocardium are not known. Hence the aim of the present study was to investigate whether DM and a PPAR-γ agonist [RGZ (rosiglitazone)] modulated the effects of hypertension on myocardial expression of PPAR isoforms. Cardiac PPAR isoforms, TNF (tumour necrosis factor)-α and IL (interleukin)-6 were evaluated by real-time PCR and Western blotting in SHRs (spontaneously hypertensive rats), diabetic SHRs, diabetic SHRs treated with RGZ (5 mg/kg of body weight) and control WKY (Wistar-Kyoto) rats. Cardiac NADPH oxidase activity was quantified using a SOD (superoxide dismutase)-sensitive cytochrome c reduction assay. When compared with hearts from control WKY rats, hearts from SHRs had decreased PPAR-α and PPAR-δ mRNA and protein levels (39 and 44% respectively for PPAR-α, and 37 and 42% respectively for PPAR-δ), but had increased PPAR-γ mRNA and protein levels (1.9- and 1.4-fold respectively). The hypertension-induced changes in mRNA and protein of cardiac PPAR isoforms were enhanced in diabetic SHRs, which were attenuated in diabetic SHRs treated with RGZ. Cardiac TNF-α and IL-6 protein levels and NADPH oxidase activities were increased in SHRs and were increased further in diabetic SHRs. RGZ treatment decreased TNF-α and IL-6 protein levels and NADPH oxidase activities in hearts from diabetic SHRs. In conclusion, these findings suggest that DM and the PPAR-γ agonist modulated the hypertensive effects on cardiac PPAR isoform expression.

Sodium hydrosulphide restores tumour necrosis factor‐α‐induced mitochondrial dysfunction and metabolic dysregulation in HL‐1 cells

“…PGC‐1α is coactivated with members of the PPAR nuclear receptor transcription factor superfamily to activate gene expression involved in mitochondrial fatty acid oxidation . We found a significant decline in both PPAR‐α and PPAR‐δ proteins in parallel to the results of our previous investigations, probably because of the compensatory response to insulin resistance caused by TNF‐α during inflammation . Similar to our previous studies, our study demonstrated that TNF‐α increases PPAR‐γ expression in cardiomyocytes, which might result in cardiac lipotoxicity through its lipogenic effect.…”

Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus

“…It is possible that adult SHR already have increased basal levels of NADPH oxidase activity and AGEs [86, 87] which could not be modulated by diabetes or apocynin. In fact, 3-month old diabetic SHR presented higher cardiac NADPH oxidase activity than control SHR [88]. Thus, apocynin reduced myocardial oxidative stress in SHR-DM-APO through mechanisms not involving NADPH oxidase activity.…”

PPARs modulate cardiac metabolism and mitochondrial function in diabetes

“…Moreover, we found increases in protein and messenger (m) RNA expressions of PPAR-γ, but decreases in protein and mRNA expressions of PPAR-α and PPAR-δ in hypertensive hearts. Diabetic spontaneously hypertensive rats were associated with greater reductions in cardiac PPAR-α and PPAR-δ, but higher increases in PPAR-γ mRNA and protein levels than were spontaneously hypertensive rats [11]. Diabetic cardiomyopathy is associated with an increase in cardiac PPAR-γ and a decrease in PPAR-α, resulting in altered glucose transportation, increased cardiac lipid accumulation, and progressive diabetic cardiomyopathy [7, 10–12].…”