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STATE-OF-THE-ART PAPER

Alcohol and the Cardiovascular System

Research Challenges and Opportunities

Diane L. Lucas, PhD^_*, Ricardo A. Brown, PhD^_*, Momtaz Wassef, PhD and Thomas D. Giles, MD^,_*

^_* Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland
Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana

Manuscript received September 25, 2004; revised manuscript received February 9, 2005, accepted February 22, 2005.

^_* Reprint requests and correspondence: Dr. Thomas D. Giles, Louisiana State University Health Sciences Center, School of Medicine, Cardiovascular Research Section, 1542 Tulane Avenue, Room 331E, New Orleans, Louisiana 70112. (Email: tgiles{at}lsuhsc.edu).

Excessive alcohol consumption has long been associated with cardiovascular disorders, including cardiomyopathy, hypertension, coronary artery disease, and stroke. However, recent evidence suggests that moderate alcohol intake can actually provide a measure of cardioprotection, particularly against coronary heart disease and ischemia-reperfusion injury. To explore the various dimensions of these opposing actions of alcohol, the National Institute on Alcohol Abuse and Alcoholism and the National Heart, Lung, and Blood Institute sponsored a state-of-the-art workshop on "Alcohol and the Cardiovascular System: Research Challenges and Opportunities" in Bethesda, Maryland, in May 2003. Speakers discussed the following topics: the epidemiology of alcohol and cardiovascular disease, clinical manifestations of alcohol, genetics of alcohol and cardiovascular disease, mechanisms underlying the molecular and cellular effects of alcohol, the application of new and emerging technology, and translation from discovery to therapeutic modalities of treatment. The panel concluded that future studies are needed to: 1) determine the role of genes and the environment in assessing mechanisms underlying the benefits of alcohol use and cardiovascular disease risk; 2) define the biological mechanisms underlying alcohol-induced peripheral vascular damage; 3) clarify the role of genetic variation in alcohol-metabolizing enzymes, genetic susceptibility, and pharmacogenomics in determining cardiovascular disease risk and effective treatment; 4) determine common mechanisms underlying alcohol-induced cardiovascular disease, such as oxidative stress and inflammation; 5) assess the role of insulin resistance, blood clotting, protein kinase C isoforms, and signal transduction mechanisms mediating alcohol’s beneficial effects; and 6) explore the potential of stem cells in myocardial regeneration and repair in hearts damaged by alcohol.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ADH = alcohol dehydrogenase   ALDH = acetaldehyde dehydrogenase   Apo = apoliporotein   BT = blood thrombosis   CAD = coronary artery disease   CHD = coronary heart disease   DCM = dilated cardiomyopathy   FDC = familial dilated cardiomyopathy   HDL-C = high-density lipoprotein cholesterol   HF = heart failure   IC = intermittent claudication   IDC = idiopathic dilated cardiomyopathy   IL = interleukin   IS = ischemic stroke   LDL-C = low-density lipoprotein cholesterol   MI = myocardial infarction   MSC = mesenchymal stem cells   NAD = nicotinamide adenine dinucleotide   NO = nitric oxide   PKC = protein kinase C   ROS = reactive oxygen species   SCD = sudden cardiac death   TF = tissue factor

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