Disentangling the epigenetic landscape in cardiovascular patients: a path toward personalized medicine.

Abstract

Despite significant advances in our understanding of cardiovascular disease (CVD) we are still far from having developed breakthrough strategies to combat coronary atherosclerosis and heart failure, which account for most of CV deaths worldwide. Available cardiovascular therapies have failed to show to be equally effective in all patients, suggesting that interindividual diversity is an important factor when it comes to conceive and deliver effective personalized treatments. Genome mapping has proved useful in identifying patients who could benefit more from specific drugs depending on genetic variances; however, our genetic make-up determines only a limited part of an individual's risk profile. Recent studies have demonstrated that epigenetic changes - defined as dynamic changes of DNA and histones which do not affect DNA sequence - are key players in the pathophysiology of cardiovascular disease and may participate to delineate cardiovascular risk trajectories over the lifetime. Epigenetic modifications include changes in DNA methylation, histone modifications and non-coding RNAs and these epigenetic signals have shown to cooperate in modulating chromatin accessibility to transcription factors and gene expression. Environmental factors such as air pollution, smoking, psychosocial context and unhealthy diet regimens have shown to significantly modify the epigenome thus leading to altered transcriptional programs and CVD phenotypes. Therefore, the integration of genetic and epigenetic information might be invaluable to build individual maps of cardiovascular risk and hence, could be employed for the design of customized diagnostic and therapeutic strategies. In the present review, we discuss the growing importance of epigenetic information and its putative implications in cardiovascular precision medicine.