Open AccessA Systems Biology Approach to Investigating Sex Differences in Cardiac Hypertrophy
Author(s) -
Harrington Josephine,
Fillmore Natasha,
Gao Shouguo,
Yang Yanqin,
Zhang Xue,
Liu Poching,
Stoehr Andrea,
Chen Ye,
Springer Danielle,
Zhu Jun,
Wang Xujing,
Murphy Elizabeth
Publication year - 2017
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.117.005838
Subject(s) - medicine , cardiac hypertrophy , cardiology , muscle hypertrophy , physiology
Background Heart failure preceded by hypertrophy is a leading cause of death, and sex differences in hypertrophy are well known, although the basis for these sex differences is poorly understood. Methods and Results This study used a systems biology approach to investigate mechanisms underlying sex differences in cardiac hypertrophy. Male and female mice were treated for 2 and 3 weeks with angiotensin II to induce hypertrophy. Sex differences in cardiac hypertrophy were apparent after 3 weeks of treatment. RNA sequencing was performed on hearts, and sex differences in mRNA expression at baseline and following hypertrophy were observed, as well as within‐sex differences between baseline and hypertrophy. Sex differences in mRNA were substantial at baseline and reduced somewhat with hypertrophy, as the mRNA differences induced by hypertrophy tended to overwhelm the sex differences. We performed an integrative analysis to identify mRNA networks that were differentially regulated in the 2 sexes by hypertrophy and obtained a network centered on PPAR α (peroxisome proliferator‐activated receptor α). Mouse experiments further showed that acute inhibition of PPAR α blocked sex differences in the development of hypertrophy. Conclusions The data in this study suggest that PPAR α is involved in the sex‐dimorphic regulation of cardiac hypertrophy.