Epigenetic Biomarkers in Cardiovascular Diseases

Abstract

Cardiovascular diseases are the number one cause of death worldwide and greatly impact quality of life and medical costs. Enormous effort has been made in research to obtain new tools for efficient and quick diagnosis and predicting the prognosis of these diseases. Discoveries of epigenetic mechanisms have related several pathologies, including cardiovascular diseases, to epigenetic dysregulation. This has implications on disease progression and is the basis for new preventive strategies. Advances in methodology and big data analysis have identified novel mechanisms and targets involved in numerous diseases, allowing more individualized epigenetic maps for personalized diagnosis and treatment. This paves the way for what is called pharmacoepigenetics, which predicts the drug response and develops a tailored therapy based on differences in the epigenetic basis of each patient. Similarly, epigenetic biomarkers have emerged as a promising instrument for the consistent diagnosis and prognosis of cardiovascular diseases. Their good accessibility and feasible methods of detection make them suitable for use in clinical practice. However, multicenter studies with a large sample population are required to determine with certainty which epigenetic biomarkers are reliable for clinical routine. Therefore, this review focuses on current discoveries regarding epigenetic biomarkers and its controversy aiming to improve the diagnosis, prognosis, and therapy in cardiovascular patients.

Keywords: atherosclerosis; biomarker; cardiovascular diseases; epigenetics; heart failure; hypertension; microRNA; myocardial infarction.

Figure 1

Epigenetic regulatory mechanisms. Posttranslational modifications of histone tails by acetylation, deacetylation, ubiquitination, methylation, and phosphorylation. DNA methylation by DNA methyltransferases (DNMTs). Posttranscriptional regulation of gene expression by microRNAs. Epigenetic modifications involve silencing or downregulation/upregulation of gene expression. Dysregulation of the epigenetic machinery could lead to gene expression dysregulation and cardiovascular diseases. Ubiquitin (Ub), methionine (Me), acetyl group (Ac), phosphate (P), deubiquitinating enzyme (DUB), histone methyltransferase (HMTs), histone demethylase (HDMTs), histone acetyltransferase (HAT), histone deacetylase (HDAC), a cytosine followed by a guanine (CpG), microRNAs (miRNAs), and messenger RNA (mRNA).

Figure 2

Epigenetic modifications and microRNAs biomarkers dysregulated in atherosclerosis and hypertension. Ascending arrows indicate higher levels or upregulation, and descending arrows denote lower levels or downregulation, both compared to control conditions. Those miRNAs presenting opposite results are shown in orange.

Figure 3

Epigenetic modifications and microRNAs biomarkers dysregulated in myocardial infarction and heart failure. Ascending arrows indicate higher levels or upregulation, and descending arrows denote lower levels or downregulation, both compared to control conditions. Those miRNAs presenting opposite results are shown in orange.