Highly reactive molecules with an unpaired electron are known as free radicals. They collide with other molecules and set up a chain reaction by either passing on the unpaired electron to the neighbouring molecule or getting quenched by it. In biological systems, the most damaging free radicals are the oxygen radicals – also termed as the reactive oxygen species [ROS] – namely superoxide, hydroxyl, and perhydroxyl. Oxidation/peroxidation of lipids, DNA bases and structural membranes through these radicals results in different pathological events depending on the site of oxidation.
These radicals are derived mostly from within our body through several well-known mechanisms, and, to counter their effects, the body has a well-established anti-oxidant system. In physiological situations, the two are in equilibrium. However, when there is an imbalance between these oxidants and anti-oxidants, pathology results.
Of all tissues, the myocardium is the most susceptible to oxidative damage as they harbour a high density of mitochondria, the powerhouses of the cells wherein oxidative phosphorylation occurs. One of the mechanisms of oxidative pathology is through epigenetic modifications, the three major types of epigenetic mechanisms being methylation/demethylation, acetylation/de-acetylation and histone modification. Whichever mechanism is involved, the result is altered gene expression. This may occur in the embryo, the fetus, the infant or the adult. At each stage, the consequences are different.
Broadly speaking, epigenetic modifications during early cardiac development lead to structural deformities, whereas these modifications occurring during later development of the heart result in conduction abnormalities and arrhythmias, coronary artery malformations and valvular defects. When oxidative damage occurs later in life, the result can be arrhythmias, hypertrophic cardiomyopathies, congestive cardiac failure and myocardial infarction. Lipid peroxidation coupled with oxidative damage to the basement membrane of blood vessels leads to coronary artery remodelling with resultant atherothrombosis and myocardial infarction.
This chapter details the mechanisms involved and the possible therapeutic implications thereof.
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