Cardiovascular Changes Related to Metabolic Syndrome: Evidence in Obese Zucker Rats.

Ilenia Martinelli,Seyed Khosrow Tayebati,Carlo Cifani,Proshanta Roy,Francesco Amenta,Daniele Tomassoni,Michele Moruzzi

doi:10.3390/ijms21062035

Ilenia Martinelli, Seyed Khosrow Tayebati + Show 5 more

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https://doi.org/10.3390/ijms21062035

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Abstract

Metabolic syndrome (MetS) is a predictor of cardiovascular diseases, commonly associated with oxidative stress and inflammation. However, the pathogenic mechanisms are not yet fully elucidated. The aim of the study is to evaluate the oxidative status and inflammation in the heart of obese Zucker rats (OZRs) and lean Zucker rats (LZRs) at different ages. Morphological and morphometric analyses were performed in the heart. To study the oxidative status, the malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), protein oxidation, and antioxidant enzymes were measured in plasma and heart. To elucidate the inflammatory markers involved, immunohistochemistry and Western blot were performed for cellular adhesion molecules and proinflammatory cytokines. OZRs were characterized by hypertension, hyperlipidemia, hyperglycemia, and insulin resistance. The obesity increased MDA and decreased the activities of superoxide dismutase (SOD) in plasma as well as in the heart, associated with cardiomyocytes hypertrophy. OxyBlot in plasma and in heart showed an increase of oxidativestate proteins in OZRs. Vascular cell adhesion molecule-1, interleukin-6, and tumor necrosis factor-α expressions in OZRs were higher than those of LZRs. However, these processes did not induce apoptosis or necrosis of cardiomyocytes. Thus, MetS induces the lipid peroxidation and decreased antioxidant defense that leads to heart tissue changes and coronary inflammation.

Highlights

Obesity is a chronic pathological condition with an accumulation of adipose tissue [1]
Human obesity is not perfectly mimed by obese Zucker rats (OZRs), these animals have been useful in understanding the causes and mechanisms that arise due to obesity and that contribute to the associated morbidity and mortality [34]
The present study demonstrates that OZRs share many features with human metabolic syndrome (MetS) [35]: obesity, insulin resistance (IR), hyperlipidemia, and elevated blood pressure [31]

Summary

Introduction

Obesity is a chronic pathological condition with an accumulation of adipose tissue [1]. It has been documented as a primary factor in the pathogenesis for several diseases [2,3]. Epicardial fat accumulates and it changes its biological characteristics. It adopts many of the features of white adipose tissue, whose inclination to lipolysis leads to the release of fatty acids and reactive inflammation. Obese animals and people exhibited high levels of TNF-α, IL-1β, and IL-6, all produced by macrophages derived from adipose tissue [14], in which endothelial cells increased adhesion proteins, such as intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin [15]. Adhesion molecules play a central role in adherence of cells to endothelial surfaces, in the integrity of the vascular wall and can be modulated by dietary pattern and body composition [16]

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