Proteomic differences associated to cardiovascular disease among apparently healthy women with previous spontaneous preterm birth
E Taufer Cederlof, Y Dan, A K Wikstrom, S Lager, A Larsson, I Sundstrom Poromaa, M Aberg, C ChristerssonAbstract
Background
Women with spontaneous preterm birth have an increased risk of cardiovascular disease (CVD) later in life. Biological pathways underlying the association are partly unknown.
Purpose
To identify possible pathways to CVD in women with history of spontaneous preterm birth by exploring differences in their proteome compared to matched controls.
Methods
Study participants were recruited from the population-based Uppsala Biobank of Pregnant Women. Cases of 100 nulliparous women with spontaneous preterm birth and 100 matched controls were invited to a follow-up visit post-pregnancy. Post-pregnant plasma samples were collected and analysed using the Olink Explore HT assay, which includes 5,416 proteins. Differential protein expression between groups were analysed, and enriched biological processes were evaluated using the full proteomic dataset via pre-ranked gene set enrichment assay (GSEA).
Results
Among the 200 women invited, 64 agreed to participate (35 cases and 29 controls) with a median follow-up time of 11.8 years since pregnancy. The mean age at pregnancy was 30.3 (Standard deviation (SD)=4.9) years and the mean age at follow-up was 41.4 (SD=5.4) years. Principal component analysis (PCA) showed no clear separation between cases and controls. A total of 34 proteins were identified as significantly altered in cases compared to controls, and several of these are known to be associated with CVD. Pre-ranked GSEA was used to investigate which biological processes that distinguish cases from controls; analyses suggested potential alteraltions in cellular processes linked to cardiac contractiliy and exicitability as well as cardiac remodelling.
Conclusion
In this explorative study, proteins reflecting vascular haemostasis and cardiac remodelling were altered in women with previous spontaneous preterm birth. Additional studies of the biological functions of these proteins and whether they can be a tool in clinical evaluation is warranted, potentially identifying women in need of enhanced cardiovascular prevention.FlowchartNetwork plot