Down-regulation of fibroblast growth factor 2 and its co-receptors heparan sulfate proteoglycans by resveratrol underlies the improvement of cardiac dysfunction in experimental diabetes

Abstract

Cardiac remodeling in diabetes involves cardiac hypertrophy and fibrosis, and fibroblast growth factor 2 (FGF2) is an important mediator of this process. Resveratrol, a polyphenolic antioxidant, reportedly promotes the improvement of cardiac dysfunction in diabetic rats. However, little information exists linking the amelioration of the cardiac function promoted by resveratrol and the expression of FGF2 and its co-receptors, heparan sulfate proteoglycans (HSPGs: Glypican-1 and Syndecan-4), in cardiac muscle of Type 2 diabetic rats. Diabetes was induced experimentally by the injection of streptozotocin and nicotinamide, and the rats were treated with resveratrol for 6 weeks. According to our results, there is an up-regulation of the expression of genes and/or proteins of Glypican-1, Syndecan-4, FGF2, peroxisome proliferator-activated receptor gamma and AMP-activated protein kinase in diabetic rats. On the other hand, resveratrol treatment promoted the attenuation of left ventricular diastolic dysfunction and the down-regulation of the expression of all proteins under study. The trigger for the changes in gene expression and protein synthesis promoted by resveratrol was the presence of diabetes. The negative modulation conducted by resveratrol on FGF2 and HSPGs expression, which are involved in cardiac remodeling, underlies the amelioration of cardiac function.

Pituitary adenylate cyclase-activating polypeptide ameliorates vascular dysfunction induced by hyperglycaemia

“…32 In a recent study, the role of FGF basic was suggested in type 2 diabetic rats where upregulation of expression of FGF basic proteins were shown. 33 In that study, resveratrol promoted the attenuation of left ventricular diastolic dysfunction by decreasing FGF basic. MMP-9 is a dysglycaemia marker 34 that fits with an early stage of cardiovascular disease as MMPs are synthetized in atherosclerotic plaques, and MMP activity is correlated with unstable angina and plaque rupture.…”

Early changes in myocyte contractility and cardiac function in streptozotocin-induced type 1 diabetes in rats

“…T1DM was modeled with a single injection of STZ (50 mg/kg, Sigma-Aldrich, St. Louis, MO, USA) dissolved in citrate buffer (0.01 M, pH 4.5) as previously described [23]. Glucose blood levels and body weights were measured after a 4-hour fasting period.…”

Combinatorial proteomics and transcriptomics identify AMPK in the control of the axonal regeneration programme of DRG sensory neurons after spinal injury

“…In fact, we found enrichment for AMPK regulatory mechanisms including ATP and adenyl ribonucleotide signalling, for AMPK-dependent classical metabolic pathways such as carbohydrate, amino acid metabolism 39,47,49,50 , and for adipocytokine signalling 51,52 .…”

“…Interestingly, several of these signalling pathways previously implicated in axonal regeneration have been found to be regulated by AMPK. They include neurotrophin, insulin, mTOR, JAK-STAT, MAPK, ErbB and VEGF signalling [26][27][28][43][44][45][46] , while others are related to AMPK-dependent metabolic regulation such as carbohydrate, amino acid metabolism 26,[47][48][49][50] or adipocytokine signalling 51,52 .…”