Remote blood sampling differential protein expression associated with persistent hypertension following a hypertensive disorder of pregnancy

ObjectiveHypertensive disorders of pregnancy are associated with future cardiovascular risk, however, the underlying mechanisms are unclear. We sought to test the feasibility of postpartum remote blood sampling following a hypertensive disorder of pregnancy and subsequently identify differentially expressed proteins in individuals who developed hypertension. Study designWe used data from a randomized clinical trial evaluating the feasibility of lifestyle intervention and home blood pressure monitoring of individuals with pre-pregnancy body mass index [&ge;]25 kg/m2 and new-onset hypertensive disorders of pregnancy. Blood pressure was measured at remote visits at 6 weeks and 1 year postpartum and blood microsamples were collected at the second remote visit. Mass spectrometry was used to quantify 381 proteins, from which differential expression and pathway enrichment analyses were performed to detect alterations with persistent hypertension. ResultsOf the 100 randomized individuals, 87 completed sample collection with 85 yielding usable proteomics data. 4 proteins were differentially expressed with false discovery rate < 0.05 in individuals not taking antihypertensive medications who developed Stage 2 hypertension: Complement C4-B (C4B) and inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) levels were elevated while Afamin (AFM) and myosin light chain 6 (MYL6) levels were decreased. Pathway enrichment analysis suggests a shared function of inhibition of endopeptidases (such as Neprilysin, which degrades natriuretic peptides) in upregulated proteins and ubiquitin-proteasome mediated proteolysis activity in downregulated proteins. ConclusionsHome microsampling is a promising methodology for postpartum sample collection. Serum proteomics using this approach suggest that protein homeostasis may be dysregulated in persistent hypertension following hypertensive disorders of pregnancy, providing novel candidates for future interventions. Condensation page1) Tweetable statement: a short condensation of the paper, consisting of no more than 210 characters, stating its essential point(s). Proteomic analysis reveals that de novo hypertension after hypertensive disorders of pregnancy correlates with dysregulated protein homeostasis. 3) AJOG at a Glance: This section only applies to Original Research and Systematic Review submissions. This section is limited to no more than 130 words, 1-3 short sentences or phrases in bullet form, briefly describing your study, its significance, and its contribution to the literature. Authors should minimize the use of abbreviations (only very commonly used abbreviations will be allowed) and define an abbreviation prior to use in this section. Responses should be listed in bullet form after the A., B., and C. headings as below (not in paragraph form). All responses are subject to minor editorial alterations and/or shortened without the authors approval, and published both in print and on the Journal website. A. Why was this study conducted?O_LIPrioritization of newborn care during the early postpartum months makes in-person research study visits challenging, necessitating improved methodologies. C_LIO_LIPersistent postpartum hypertension may mediate the established relationship between hypertensive disorders of pregnancy and future cardiovascular disease risk, yet its pathogenesis remains poorly understood. C_LI B. What are the key findings?O_LIHome microsampling is a promising methodology for postpartum sample collection. C_LIO_LISerum proteomics using this approach suggest that protein homeostasis may be dysregulated in persistent hypertension following hypertensive disorders of pregnancy. C_LI What does this study add to what is already known?O_LIOur findings suggest that certain known features of hypertensive disorders of pregnancy, such as coagulation cascade activation, alterations of serum Afamin and proteasome levels, and protease dysregulation, might persist and contribute to de novo postpartum hypertension. C_LIO_LISome of these pathways may be amenable to future intervention development to prevent persistent hypertension after a hypertensive disorder of pregnancy. C_LI