Prevention of Arterial Stiffening by Using Low-Dose Atorvastatin in Diabetes Is Associated with Decreased Malondialdehyde

Chih-Hsien Wang,Wen-Je Ko,Ru-Wen Chang,Tai-Horng Young,Shoei-Shen Wang,Ya-Hui Ko,Yih-Sharng Chen,Kuo-Chu Chang,Chun-Yi Chang,Pi-Ru Tsai,Lynette K Rogers

doi:10.1371/journal.pone.0090471

Chih-Hsien Wang, Wen-Je Ko + Show 9 more

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https://doi.org/10.1371/journal.pone.0090471

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Abstract

IntroductionWithout affecting the lipid profile, a low-dose treatment with atorvastatin contributes to the reduction of oxidative stress, inflammation, and adverse cardiovascular events in diabetes. In this study, we investigated whether low-dose atorvastatin exerts any beneficial effect on vascular dynamics in streptozotocin (STZ)-induced diabetes in male Wistar rats.MethodsDiabetes was induced using a single tail-vein injection of STZ at 55 mg kg−1. The diabetic rats were treated daily with atorvastatin (10 mg kg−1 by oral gavage) for 6 weeks. They were also compared with untreated age-matched diabetic controls. Arterial wave reflection was derived using the impulse response function of the filtered aortic input impedance spectra. A thiobarbituric acid reactive substances measurement was used to estimate the malondialdehyde content.ResultsThe high plasma level of total cholesterol in the diabetic rats did not change in response to this low-dose treatment with atorvastatin. Atorvastatin resulted in a significant increase of 15.4% in wave transit time and a decrease of 33.5% in wave reflection factor, suggesting that atorvastatin may attenuate the diabetes-induced deterioration in systolic loads imposed on the heart. This was in parallel with its lowering of malondialdehyde content in plasma and aortic walls in diabetes. Atorvastatin therapy also prevented the diabetes-related cardiac hypertrophy, as evidenced by the diminished ratio of left ventricular weight to body weight.ConclusionThese findings indicate that low-dose atorvastatin might protect diabetic vasculature against diabetes-associated deterioration in aorta stiffness and cardiac hypertrophy, possibly through its decrease of lipid oxidation-derived malondialdehyde.

Highlights

Without affecting the lipid profile, a low-dose treatment with atorvastatin contributes to the reduction of oxidative stress, inflammation, and adverse cardiovascular events in diabetes
Persistent hyperglycemia results in the formation of advanced glycation end products (AGEs), which leads to increased oxidative stress [5]
After exposure to Ator, the DM demonstrated a significant increase in body weight (BW), but did not differ in LV weight (LVW) compared with the untreated diabetic controls

Summary

Introduction

Without affecting the lipid profile, a low-dose treatment with atorvastatin contributes to the reduction of oxidative stress, inflammation, and adverse cardiovascular events in diabetes. An increase in oxidative chemical modifications of tissue proteins has been implicated in the pathogenesis of diabetes mellitus [1,2]. Persistent hyperglycemia results in the formation of advanced glycation end products (AGEs), which leads to increased oxidative stress [5]. Malondialdehyde (MDA) is a highly toxic by-product formed in part by lipid peroxidation derived free radicals [6,7]. The pathogenic cross-linking of collagen through MDA may affect tissue remodeling and result in loss of elasticity, contributing to the development of certain physical changes of the vasculature Slatter et al [8,9] have shown that MDA can react with long-lived proteins, such as glycated collagen to form MDA-collagen cross-links that stabilize the collagen but render it susceptible to further glycation.

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