Abstract

BackgroundChanges in the proteoglycans glypican and syndecan-4 have been reported in several pathological conditions, but little is known about their expression in the heart during diabetes. The aim of this study was to investigate in vivo heart function changes and alterations in mRNA expression and protein levels of glypican-1 and syndecan-4 in cardiac and skeletal muscles during streptozotocin (STZ)-induced diabetes.MethodsDiabetes was induced in male Wistar rats by STZ administration. The rats were assigned to one of the following groups: control (sham injection), after 24 hours, 10 days, or 30 days of STZ administration. Echocardiography was performed in the control and STZ 10-day groups. Western and Northern blots were used to quantify protein and mRNA levels in all groups. Immunohistochemistry was performed in the control and 30-day groups to correlate the observed mRNA changes to the protein expression.ResultsIn vivo cardiac functional analysis performed using echocardiography in the 10-day group showed diastolic dysfunction with alterations in the peak velocity of early (E) diastolic filling and isovolumic relaxation time (IVRT) indices. These functional alterations observed in the STZ 10-day group correlated with the concomitant increase in syndecan-4 and glypican-1 protein expression. Cardiac glypican-1 mRNA and skeletal syndecan-4 mRNA and protein levels increased in the STZ 30-day group. On the other hand, the amount of glypican in skeletal muscle was lower than that in the control group. The same results were obtained from immunohistochemistry analysis.ConclusionOur data suggest that membrane proteoglycans participate in the sequence of events triggered by diabetes and inflicted on cardiac and skeletal muscles.

Highlights

  • Changes in the proteoglycans glypican and syndecan-4 have been reported in several pathological conditions, but little is known about their expression in the heart during diabetes

  • We examined the mRNA expression and the amount of 2 key cell surface heparan sulfate chain-carrying core proteins, syndecan-4 and glypican-1, after 24 hours, 10 days, and 30 days of STZ-induced experimental diabetes in 2 muscles, cardiac and skeletal

  • Body weight was significantly lower in 10-day and 30-day groups compared with control animals according to analysis of variance (ANOVA) followed by the Tukey Multiple Comparison Test: 217.4 ± 3.9 g and 222.4 ± 9.53 g vs 265.8 ± 10.9 g, P < 0.05

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Summary

Introduction

Changes in the proteoglycans glypican and syndecan-4 have been reported in several pathological conditions, but little is known about their expression in the heart during diabetes. The aim of this study was to investigate in vivo heart function changes and alterations in mRNA expression and protein levels of glypican-1 and syndecan-4 in cardiac and skeletal muscles during streptozotocin (STZ)-induced diabetes. Diabetes mellitus is a complex disorder resulting in largeand small-vessel disease and impaired organ function. It is characterized by hyperglycemia and by a variety of end-organ damage [1]. One of the major causes of morbidity and mortality in diabetic patients is the cardiovascular disease related to the myocardial contractile system [2], with diastolic dysfunction being an early event of diabetic cardiomyopathy, preceded by a change in cardiac metabolism [3,4]. Several mechanisms were proposed to explain the installation of the disease, but the main changes are promoted by hyperglycemia, and represent an adaptive or maladaptive response that culminates in the installation of this clinical entity [5]

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