Blood transcriptomic signature associated with hypertension in females across two human cohorts
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
Hypertension prevalence rises sharply in females after menopause, exceeding that of age-matched males in later life, conferring greater relative cardiovascular disease risk in females than in males. However, the underlying mechanisms remain poorly understood.
Method
We studied multi-tissue RNA-sequencing data from 193 CVD-free participants aged >55 years in the GTEx database and extended the findings to 1,605 age-matched Framingham Heart Study participants.
Results
We identified a dominant female hypertension co-expression signature in blood, expressed at lower levels in females with uncontrolled high blood pressure than in males (sex-by-hypertension interaction) in both cohorts. Genes contributing to this signature were enriched for post-transcriptional modification and insulin signalling and regulated by ETS family transcription factors (TFs). Ten ETS TFs showed the same female-specific hypertension association and together explained the signature’s expression. Moreover, in females, but not males, lower blood signature scores were associated with a pro-inflammatory transcriptome in the artery and kidneys.
Conclusions
Collectively, we identified the ETS-transcriptomic axis as a potential mechanism explaining sex differences in human hypertension.
Graphic Summary
