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Review
. 2018 Dec;72(6):1244-1254.
doi: 10.1161/HYPERTENSIONAHA.118.11171.

Epigenetic Mechanisms and Hypertension

Mingyu Liang  1
Affiliations
Review

Epigenetic Mechanisms and Hypertension

Mingyu Liang. Hypertension. 2018 Dec.
No abstract available

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Figures

Figure 1.
Figure 1.. Epigenetic mechanisms’ role in disease mechanisms.
A disease can arise from the expression of mutated proteins, stable changes in gene expression levels, or other abnormalities, including transient changes in gene expression, post-transcriptional or post-translational changes in proteins and changes in other chemical or physical factors. Stable changes in gene expression can occur because of variations in DNA regulatory sequences or effects of environment and lifestyle factors. Epigenetic mechanisms underlie stable changes in DNA function that variations in the sequence of the DNA do not determine directly. Such changes can respond to environment and lifestyle factors dynamically and can result from DNA-environment interactions.
Figure 2.
Figure 2.. Several DNA regions spanning chromosome 13 are in physical proximity of the renin proximal promoter.
The contact map shown derives from a 4C-seq analysis of rat cardiac microvascular endothelial cells. Top: Blue lines indicate contacts between Ren proximal promoter and distant interacting regions on chromosome 13. Bottom: Contacts with the Ren proximal promoter within 1 Mb of the viewpoint. Location of the Ren proximal promoter viewpoint is indicated with a dashed red line. Red fragments labeled “Exact Interaction” have significant contact with the Ren proximal promoter in multiple samples analyzed. Reproduced from Stodola et al.
Figure 3.
Figure 3.. A tree-like paradigm for understanding the mechanisms underlying complex traits and diseases.
The large number of molecular changes, including epigenetic changes, involved in a complex trait, such as BP, are like leaves on a tree that will merge gradually into small and then large branches. Cellular signaling and metabolic pathways are the small branches, and physiological pathways are the large branches. In the case of BP, the pathways ultimately will influence cardiac output or peripheral vascular resistance, the final determinants of BP. The arrows in the graph illustrate the concept of convergence that is fundamental to this tree-like paradigm. Divergence, cross-talks and feedback loops are not depicted, but could contribute importantly to the regulatory network.
Figure 4.
Figure 4.. The emerging discipline of systems molecular medicine.
To construct the regulatory network underlying a complex physiological trait or disease, comprehensive molecular profiles, including epigenetic profiles, with sufficient spatial and temporal resolution need to be obtained from patients and clinically relevant models. The molecular compendia will have to be analyzed with a systems view, with respect to both the relations among molecules and in the context of organ systems function. Informative perturbations will need to be applied, followed by reiterations of molecular and systems analyses, to reveal and validate the underlying regulatory network. The discipline of systems molecular medicine is emerging from the intersection of several concepts and disciplines including systems biology, physiology, genomics, translational research, and precision medicine.
See this image and copyright information in PMC

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