Epigenomic processes are believed to play a pivotal role for the effect of environmental exposures in early life to modify disease risk throughout the lifespan. Offspring of women with hypertensive complications of pregnancy (HTNPREG) have an increased risk of developing systemic and pulmonary vascular dysfunction in adulthood. In this preliminary report, we sought to determine whether epigenetic modifications of genes involved in the regulation of vascular function were present in HTNPREG offspring. We contrasted DNA methylation and gene expression patterns of peripheral blood mononuclear cells obtained from young male offspring of HTNPREG (n = 5) to those of normotensive controls (n = 19). In HTNPREG offspring we identified six differentially methylated regions (DMRs) including three genes (SMOC2, ARID1B and CTRHC1) relevant to vascular function. The transcriptional activity of ARID1B and CTRCH1 was inversely related to methylation status. HTNPREG offspring had higher systolic pulmonary artery pressure (sPPA) versus controls. Our findings demonstrate that epigenetic marks are altered in offspring of HTNPREG with a modest elevation of sPPA and introduce novel epigenomic targets for further study. On the basis of these findings we speculate that epigenomic mechanisms may be involved in mediating the effect of HTNPREG to raise the risk of vascular disease later in life.
Bibliographical noteFunding Information:
We would like to acknowledge all the individuals who participated in this project as research subjects and the physicians and technical staff at the Bolivian Institute of High Altitude Biology. Support for data collection and analysis was obtained from grants NIH-HL079647 (L. G. M.), R03TW007957 from the Fogarty International Center (L. G. M. and C. G. J.), NIH-HL095393 (D. A. S.), NIH-HL101715, (D. A. S.), NIH-ES18181 (D. A. S.) and the NIH/NCATS Colorado CTSA UL1 TR001082 (CMH-Pilot, C. G. J.). C. G. J. is supported by the NIH BIRCWH program (5 K12HD057022-07).
© 2015 Wiley Periodicals, Inc.
- Developmental programming
- Gestational hypertension