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Role of Epigenetics in Blood Pressure Regulation and Development of Hypertension
Hypertension is a clinical manifestation of complex multigenic, pathophysiological, and environmental factors. Despite extensive work, there is still much to learn about its initiating causes, pathogenic mechanisms, and the pathways by which it predisposes to its well-known complications, such as heart failure, heart attack, heart disease, recurrent strokes, diabetes and chronic kidney disease. While antihypertensive medications and lifestyle modifications make it possible to reduce the risks of hypertensive complications, to date we do not know how to prevent or “cure” the disease. Recently, investigators are focusing on epigenetics as a means to better understand the causes, progression, and possible prevention of hypertension.
To explore the potential correlation between epigenetic modifications of genomic DNA and the development of hypertension, NHLBI convened a working group of multidisciplinary experts in Bethesda, Maryland on June 27-28, 2011. A major challenge in the field of epigenetics is the disentangling of causal pathways, i.e., epigenetic DNA modifications can induce disease, but disease can also induce epigenetic modifications. We know that some epigenetic modifications can be acquired, while others may be inherited. The working group was asked to review the state of knowledge in hypertension and epigenetics, as well as in several related fields; consider the potential for a causal relationship; and identify gaps in current knowledge and resources.
Gaps in Knowledge and Resources
The working group identified several gaps in current knowledge:
- It is not known whether epigenetic modifications can cause and/or increase the risk of developing hypertension. Experimental studies in appropriate animal models could generate specific hypotheses (e.g., by looking at temporal sequences of hypertensive phenotype and epigenetic changes during normal development and onset of hypertension, or through investigation of associations in “experiments of nature” in humans) or test hypotheses regarding fundamental molecular mechanisms. Comparisons across species will be needed.
- It is not known how epigenetic modifications interact with environmental exposures in people with or at risk for hypertension. Future studies could assess interactions through investigation of large human family cohorts, twin studies and comparative animal models.
- It is not known to what degree phenotypically important epigenetic modifications are heritable. Investigators could explore the heritability and trans-generational transmission of hypertension-associated epigenetic changes using animal models and human cohorts (e.g., twin and multigenerational studies). These studies may also be relevant to obesity and related metabolic conditions.
- It is not known which epigenetic features can serve as predictive, diagnostic, or prognostic biomarkers in hypertension.
The working group also identified resources needed to enable studies relating hypertension to epigenetic modifications:
- Biobanks and databases for collection and dissemination of comparative experimental and clinical samples and information
- Computational methods facilitating integration of complex layers of information
- Technologies for analysis of single cells and specific cell populations in vivo, and to introduce or remove epigenetic modifications
- Establishment and support of multidisciplinary investigative teams
A manuscript in a peer-reviewed journal is planned in 2012.
Working Group Members
- Allen W. Cowley, Jr., PhD, Medical College of Wisconsin
- Joseph Nadeau, PhD, Institute for Systems Biology
- Andrea Baccarelli, MD, MPH, Harvard School of Public Health
- Kathleen Berecek, PhD, University of Alabama at Birmingham
- Myriam Fornage, PhD, University of Texas Health Sciences Center at Houston
- Gary H. Gibbons, MD, Morehouse School of Medicine
- David G. Harrison, MD, Vanderbilt University School of Medicine
- Mingyu Liang, PhD, Medical College of Wisconsin
- Peter W. Nathanielsz, MD, PhD, ScD, FRCOG, University of Texas Health Science Center at San Antonio
- Daniel T. O’Connor, MD, University of California at San Diego
- Jose Ordovas, PhD, Jean Mayer USDA HNRCA at Tufts University
- Weiqun Peng, PhD, George Washington University
- Marcelo Bento Soares, PhD, Northwestern University’s Feinberg School of Medicine
- Moshe Szyf, PhD, McGill University
- Keji Zhao, PhD, National Institutes of Health
- Katherine C. Wood, PhD
- Zorina Galis, PhD
- H. Eser Tolunay, PhD
- Terry Thrasher, PhD
- Pothur Srinivas, PhD, MPH
- Michelle Olive, PhD
- Cashell Jaquish, PhD
- Cristina Rabadan-Diehl, PhD, MPH
Last Updated: August 2012