Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK

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Mitochondria-Targeted Antioxidants as a Therapeutic Strategy for Protecting Endothelium in Cardiovascular Diseases

Author(s): Nadezda Apostolova, Milagros Rocha, Susana Rovira-Llopis, Celia Banuls, Rosa Falcon, Raquel Castello, Antonio Hernandez-Mijares, Victor M. Victor.

Abstract:

Endothelial dysfunction involving dysfunctional mitochondria precedes the development of cardiovascular diseases. This impairment results from an increase in reactive oxygen species, which leads to oxidative stress and a reduced bioavailability of nitric oxide. It has been demonstrated that oxidative stress and alterations in glucose and lipid homeostasis (e.g. hyperinsulinemia, hyperglycemia, insulin resistance and dyslipidemia) are linked to mitochondrial impairment and that all of them contribute to endothelial dysfunction. Anti-hyperlipidemic drugs such as statins, anti-hypertensive drugs and angiotensin receptor antagonists have been shown to exert protection through anti-oxidative stress mechanisms. Other substances with antioxidant properties, such as vitamins, are also capable of abolishing the oxidative stress associated with cardiometabolic diseases. However, the results obtained with general antioxidants in clinical trials are contradictory, perhaps due to the unspecific nature of the targets selected. This study correlates endothelial dysfunction and mitochondrial dysfunction and examines current research for the selective targeting of specific molecules (such as ·NO donors and antioxidants) to mitochondria with the aim of protecting the endothelium against oxidative stress in cardiovascular diseases.

Keywords: Cardiovascular diseases, endothelial dysfunction, mitochondria, mitochondria-targeted antioxidants, oxidative stress.

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Article Details

VOLUME: 21
ISSUE: 25
Year: 2014
Page: [2989 - 3006]
Pages: 18
DOI: 10.2174/0929867321666140601200416
Price: $58