Symposium papers highlight role of oxidative stress in cardiovascular disease

Recent years have seen major advances in understanding of the health effects of oxidative stress—including its potential to cause injury to the cardiovascular system. A series of expert updates on the role of oxidative stress in heart failure, atherosclerosis, and other cardiovascular diseases appears in a special symposium in the August issue of The American Journal of the Medical Sciences (AJMS), official journal of the Southern Society for Clinical Investigation (SSCI). The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

The papers summarize lectures delivered at the SSCI's 2011 annual scientific session, presented by internationally recognized experts and SSCI members. From "relative obscurity" two decades ago, oxidative stress is now known to play a major role in a wide range of cardiovascular and related diseases, according to an introductory editorial by Dr. Karl T. Weber of the University of Tennessee Health Science Center.

'Oxidative Stress Causes Injury to the Cardiovasculature'

The six symposium papers outline some of the ways that oxidative stress can contribute to cardiovascular disease. Although reactive oxygen species (ROS) participate in several types of normal intracellular signaling, they can also contribute to cytotoxic (cell-killing) effects, Dr. Weber explains. Oxidative stress occurs when the balance between pro-oxidants and antioxidants is disrupted. Harmful effects include changes to lipids, proteins, and DNA—initiating processes that lead to cell death. "Oxidative stress causes injury to the cardiovasculature," Dr. Weber concludes.

A paper by Dr. Louis J. Dell'Italia of University of Alabama at Birmingham and colleagues discusses the role of oxidative stress in disease of the mitral valve of the heart. Detailed cellular analyses show that oxidative stress contributes to heart muscle damage related to mitral regurgitation. These discoveries may lead to new strategies to preventing irreversible cellular damage and optimizing the timing of valve repair surgery.

Dr. Douglas B. Sawyer of Vanderbilt University reviews the importance of oxidative stress in congestive heart failure. Animal studies suggest that treatment with antioxidants—for example vitamin C or E or resveratrol—may be useful in preventing progressive heart damage. Alternatively, new approaches might be found to control the generation of pro-oxidant ROS by damaged heart muscle cells.

Oxidative stress also contributes to the high risk of cardiovascular disease associated with low magnesium levels (hypomagnesemia), according to Dr. William Weglicki and colleagues of George Washington University. They provide insights into the "pro-oxidant/pro-inflammatory" processes resulting from prolonged hypomagnesemia—complications that are preventable through careful monitoring and correction of magnesium levels.

Dr. Weber and co-authors outline the role of oxidative stress in a mitochondriocentric pathway leading to death (necrosis) of cardiac muscle cells. Molecular-level studies suggest possible new approaches to monitoring and correcting the wide range of factors contributing to cell death in heart failure and other conditions.

Dr. Sona Mitra and colleagues of University of Arkansas review evidence linking the oxidized form of low-density lipoprotein ("bad") cholesterol to the development and progression of atherosclerosis ("hardening of the arteries"). Dr. Mitra and co-authors also highlight some issues that may explain why past attempts at antioxidant treatment have failed to prevent atherosclerosis and heart disease.

Oxidative stress is a key first step in the process of muscle wasting (cachexia), common to heart failure, diabetes, cancer, and other diseases, according to a paper by Dr. Patrice Delafontaine of Tulane University and colleagues. They discuss experiments in mice showing how oxidative stress induced by the peptide angiotensin II contributes to cachexia—which may help in identifying specific new treatments for muscle wasting.

The symposium papers highlight the many and varied ways in which pro-oxidant mediated injury contributes to cardiovascular and related diseases. Dr. Weber believes that continued research into processes by which oxidative stress causes cardiovascular injury may open the way to new pharmaceutical and "nutraceutical" approaches to combating these harmful effects.