Fetal programming as the cause of all the evils in adult humans: atherosclerosis and coronary heart disease included

Abstract

The theory of David Barker on "the fetal origin of adult diseases" is revolutionising the pathophysiology and aetiopathogenesis of adult human diseases such as atherosclerosis. Atherosclerosis and related coronary heart diseases (CHDs) appear to be the result of fetal programming, with the cardiovascular system, and particularly the endothelium component, being the principal target of this process. This suggests that cardiovascular diseases can take place during fetal development. This life period is crucial for developmentally programming body systems (such as the cardiovascular system), their ageing and disease. A sophisticated interplay of exogenous-gestational environmental factors with the fetal genome induces epigenetic changes (microRNA, DNA methylation patterns and histone structure alterations) and expression of altered phenotypes of developing systems. A poor maternal diet rich in cholesterol, diabetes, obesity, smoking and exposure to various environmental pollutants represent the major factors related to an increased risk and progression of atherosclerosis in postnatal life. The fetal cardiovascular system is susceptible to these factors, and developmental programming events cause endothelial dysfunction, small coronary arteries, stiffer vascular tree, fewer cardiomyocytes, coagulopathies and atherogenic blood lipid profiles in the fetus. Consequently, preventive interventions are recommended for both parents who want to have children, for counteracting the onset of atherosclerosis and CHDs in new generations.