ponedjeljak, 15 Januar 2018 13:41

The Epigenetics and Cardiovascular Disease

By Nermina Lamadema, Postdoctoral Research Associate at King's College London

Cardiovascular diseases (CVD) refer to the whole group of disorders that affect the heart and the blood vessels supplying heart, brain, body periphery (arms and legs) and is one of the leading causes of death worldwide. According to the WHO it is a number one cause of death globally with estimated 17.7 million people dying of the disease in 2015 majority in low and middle-income countries. As the population ages this class of disease has the potential to become even more prevalent which makes the need for better understanding of the underlaying cause and biological mechanisms of the disease even more urgent. The most commonly identified risk factors of the disease include obesity and diabetes which place the greatest burden on the health of the heart and vascular system. Apart from the genetic predispositions, and certain infectious diseases other well-established risk factors that significantly contribute to the development of the disease are related to the lifestyle choices such as for example smoking, being physically inactive, stress or drinking excessive amounts of alcohol. These behavioural choices exert their effect through intermediate risk factors such as raised blood pressure, raised blood glucose and lipids. All of these factors can be monitored to work out the risks of developing a heart attack, heart failure stroke or other vascular complications.

The heart disease develops in the wall of the blood vessels (coronary arteries) where the build-up of fatty deposits develops gradually leading to the narrowing of the vessel and reduction in the supply of oxygen and nutrients to the heart thereby impairing its function. This is called atherosclerosis and it eventually can lead to either a heart failure due to the hearts inability to properly pumps the blood around the body or if the artery blockage becomes complete myocardial infraction or heart attack when the heart becomes totally starved of oxygen.  Cardiovascular diseases cover the whole plethora of conditions ranging in severity from relatively slowly progressive ones which over the years reduce the persons quality of life to severe stage heart failure with a life expectancy similar to aggressive cancers through to strokes and heart attacks and lower extremity amputations in diabetic patient all of which places a huge economic burden on the society at large to provide sustained treatment and interventions. This is why health policies tend to focus on preventative efforts that encourage people to adopt and sustain healthy behaviour and habits. Examples of such population wide drives include measure to control the consumption of foods that are high in fat, sugar and salt as well as the availability of tobacco through comprehensive taxation policies, provision of facilities to encourage greater physical activity and provision of healthy school meals to children. Nevertheless, the search for ever more effective treatments to ease the burden of the disease is ongoing and the researchers are looking into the disease mechanisms to better understand this disease spectrum and hence provide more targeted therapies.

The case for epigenetics

In order to explore the links of the main causative agents of CVD development which can be environmental, behavioural, genetic and clinical in nature researchers rely on epidemiological studies to better understand the disease phenotype. These studies reveal as one of the most important mechanisms epigenetic factors of which DNA methylation seems to be of the greatest biological importance. Studies find that key processes implicated in CVD such as atherosclerosis, hypertension and inflammation seem to have DNA methylation changes as an underlying mechanism.  For example, comparison of the heart tissue between the healthy and heart disease patients reveals significant differences in the DNA methylation patterns between the two particularly in relation to the genes that govern angiogenesis. Other genetic regions that appear to be altered through aberrant DNA methylation include in hear failure patient’s genes that govern the function of myocyte – cardiac muscle cells as well as insulin responsive genes important in prenatal nutrition and overall global non-coding elements. Further role for the epigenetics comes from the studies of dietary and other lifestyle factors which are highly associated with the DNA methylation changes. For example, studies on dietary effects show that by manipulating nutrition particularly of methyl rich foods containing B12, folate and methionine, it is possible to affect the DNA methylation patterns of the epigenome. In mice for example the restriction of such foods gave rise to the obese insulin resistant pups compared to the healthy controls. Other factors that influence epigenome with an adverse effect on the health of the cardiovascular system include smoking, exposure to the environmental toxins and aging. Given the endemic widespread problem of smoking and high salt food intake in Bosnia and Herzegovina we would like to investigate most current research pertaining to these specific risk factors and their effect on CVD from the epigenetic perspective on the next issue of Ashq magazine.

Članak „Epigenetika i kardiovaskularne bolesti“ na bosanskom jeziku možete pročitati u 19. broju magazina AŠK, decembar 2017.

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