Focus on: The cardiovascular system: what did we learn from the French (Paradox)?

Abstract

Although heavy alcohol consumption has deleterious effects on heart health, moderate drinking is thought to have cardioprotective effects, reducing the risk of coronary artery disease and improving prognosis after a myocardial infarction. It still is unclear, however, if this effect can be achieved with all types of alcoholic beverages and results from the alcohol itself, from other compounds found in alcoholic beverages, or both. For example, the polyphenolic compound resveratrol, which is found particularly in red wine, can reduce the risk of atherosclerosis; however, it is not clear if the resveratrol levels present in wine are sufficient to achieve this result. Alcohol itself contributes to cardioprotection through several mechanisms. For example, it can improve the cholesterol profile, increasing the levels of "good" cholesterol and reducing the levels of "bad" cholesterol. Alcohol also may contribute to blood clot dissolution and may induce a phenomenon called pre-conditioning, whereby exposure to moderate alcohol levels (like short bouts of blood supply disruption [i.e., ischemia]), and result in reduced damage to the heart tissue after subsequent prolonged ischemia. Finally, the enzyme aldehyde dehydrogenase (ALDH) 2, which is involved in alcohol metabolism, also may contribute to alcohol-related cardioprotection by metabolizing other harmful aldehydes that could damage the heart muscle.

Figure 1

Molecular structure of resveratrol. Resveratrol is a polyphenol—that is, it contains several ring-like molecular building blocks known as phenols.

Figure 2

Schematic demonstrating some of the steps leading to cellular damage as a result of reactive oxygen species (ROS). (1) ROS interact with lipids in the cell membrane, (2) resulting in the formation of the aldehyde 4-hydroxynonenal (4HNE) (brown zigzag line). (3) Many proteins are inactivated as a result of 4HNE-induced adduct formation, and their removal by the proteasome (black and gray structure) is critical. However, 4HNE directly inactivates the proteasome (Farout et al. 2006). (4) Therefore, protein aggregates accumulate, further increasing oxidative stress in the cell. (5) Several mitochondrial proteins also are inactivated by 4HNE (Chen et al. 1995; Echtay and Brand 2007; Kristal et al. 1996) including those involved in electron transfer chain (ETC), (6) the citric acid cycle α-ketoglutarate dehydrogenase (KGDH), and (8) mitochondrial integrity. (9) This leads to increased mitochondria-induced ROS production, decreased ATP generation during reperfusion (Inagaki 2003), and reduced repair of the cells from the oxidative damage. This, in turn, leads to further cardiac function loss. This schematic demonstrates a critical role for enzymes that remove the toxic aldehydes, such as the aldehyde dehydrogenase (ALDH)-1 enzyme, which is found in the fluid filling the cells (i.e., the cytosol), and the ALDH2 enzyme, which is found in the mitochondria. (7) However, these ALDHs are inactivated themselves by the toxic 4HNE (Doorn et al. 2006; Luckey et al. 1999). A compound that could protect ALDH from inactivation and decrease the amounts of aldehydes in the cell should protect from damage induced by ischemia and reperfusion and other oxidative stress-induced injuries.