The role of lipotoxicity in smoke cardiomyopathy.

Priscila P Santos,Vanessa C M P Ferreira,Pamela Modesto,Meliza G Roscani,Ana Angelica Fernandes,Marcos F Minicucci,Leonardo A M Zornoff,Bruna P M Rafacho,Luiz S Matsubara,Fernando Oliveira,Silmeia G Zanati,Annarita Di Lorenzo,Paula S Azevedo,Bertha F Polegato,Sergio A R Paiva

doi:10.1371/journal.pone.0113739

Priscila P Santos, Vanessa C M P Ferreira + Show 13 more

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https://doi.org/10.1371/journal.pone.0113739

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Abstract

Background/AimsExperimental and clinical studies have shown the direct toxic effects of cigarette smoke (CS) on the myocardium, independent of vascular effects. However, the underlying mechanisms are not well known.MethodsWistar rats were allocated to control (C) and cigarette smoke (CS) groups. CS rats were exposed to cigarette smoke for 2 months.ResultsAfter that morphometric, functional and biochemical parameters were measured. The echocardiographic study showed enlargement of the left atria, increase in the left ventricular systolic volume and reduced systolic function. Within the cardiac metabolism, exposure to CS decreased beta hydroxy acyl coenzyme A dehydrogenases and citrate synthases and increased lactate dehydrogenases. Peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) were expressed similarly in both groups. CS increased serum lipids and myocardial triacylglycerols (TGs). These data suggest that impairment in fatty acid oxidation and the accumulation of cardiac lipids characterize lipotoxicity. CS group exhibited increased oxidative stress and decreased antioxidant defense. Finally, the myocyte cross-sectional area and active Caspase 3 were increased in the CS group.ConclusionThe cardiac remodeling that was observed in the CS exposure model may be explained by abnormalities in energy metabolism, including lipotoxicity and oxidative stress.

Highlights

Cigarette smoke (CS) contains more than 4000 toxic substances and is responsible for the death of almost 6 million people each year [1]
The aim of our study was to evaluate the potential mechanisms involved in the remodeling process induced by exposure to cigarette tobacco, including energy metabolism, oxidative stress, myocyte hypertrophy and apoptosis
Our data suggest that alterations in energy metabolism might be a key modulator of the remodeling process induced with smoking, which is associated with apoptosis, oxidative stress and cellular growth

Summary

Introduction

Cigarette smoke (CS) contains more than 4000 toxic substances and is responsible for the death of almost 6 million people each year [1]. Experimental and clinical studies have shown that CS induces cardiac remodeling via cardiovascular and toxic effects [2, 3, 4, 5, 6]. Rats exposed to tobacco smoke presented a different remodeling pattern associated with a drop in the systolic function [5, 7, 8, 9, 10, 11, 12]. In clinical studies, smoking has been found to be an independent risk factor for cardiac hypertrophy and dysfunction, independent of hypertension and atherosclerosis [3, 4, 13]. The vascular damage induced by CS has been intensively studied. The underlying mechanisms that link the toxic effects of CS to cardiac remodeling are not well known [6]

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