(979) Differential protein expression associated with persistent hypertension following a hypertensive disorder of pregnancy

Hypertensive disorders of pregnancy (HDP) are associated with future cardiovascular risk, however, the underlying mechanisms are unclear. We sought to identify differentially expressed proteins in individuals who developed chronic hypertension (HTN) in the first year postpartum following a HDP compared to those who remained normotensive.

Study Design:

We used data from a randomized clinical trial evaluating lifestyle intervention and home blood pressure (BP) monitoring of individuals with pre-pregnancy body mass index (BMI) ≥25 kg/m² and a new-onset HDP. The primary outcome was feasibility and no differences were seen in BP between arms, thus randomization groups were combined. BP was measured at remote research visits at 6 weeks and 1 year postpartum and blood microsamples were collected at the second visit. Mass-spectrometry was used to quantify 381 proteins, from which differential expression and pathway enrichment analyses were performed to detect alterations with persistent HTN (BP ≥140/90 mmHg). All analyses controlled for BMI, tobacco use, and the social construct of race.

Results:

Of the 100 randomized individuals, 88 (88%) completed sample collection with 85 yielding usable proteomics data. 4 proteins were differentially expressed in individuals with persistent HTN. Stage 2 HTN was associated with increased levels of Complement C4-B (C4B) and inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and decreased levels of Afamin (AFM) and the smooth muscle protein myosin light chain 6 (MYL6) compared with Stage 1 HTN or normalization of BP. Pathway enrichment analysis suggests a shared function of endopeptidase inhibitor activity (such as Neprilysin, which degrades natriuretic peptides) in upregulated proteins and ubiquitin-proteasome mediated proteolysis activity in downregulated proteins.

Conclusion:

Home microsampling is a promising methodology for postpartum sample collection. Serum proteomics using this approach suggest that protein homeostasis may be dysregulated in persistent HTN following HDP and provides novel candidates for future interventions to reduce progression to HTN following HDP.