Postpartum cardiac reverse remodeling is reflected in urine proteome

Abstract Background The impact of postpartum cardiac reverse remodeling (RR) on urinary proteome, particularly in pregnant women with cardiovascular risk (CVR) factors who show long-term increased risk of cardiovascular disease and mortality is unknown. Purpose To profile the urinary proteome in pregnant women with/without CVR factors to identify proteins associated with postpartum RR. Methods Our study included a prospective cohort of 32 healthy and 27 obese and/or hypertensive and/or diabetic pregnant women who underwent transthoracic echocardiography, pulse-wave-velocity, and urine collection at the 3rd trimester and 6-months postpartum. Shotgun HPLC-MS/MS profiled proteins. Generalized linear mixed-effects models were used to identify associations between urinary proteins and left ventricle mass (LVM), a surrogate of RR. Results The presence of at least one CVR factor was associated with worse LVM RR. We identify 6 (alpha-galactosidase A [GLA], sialate O-acetylesterase [SIAE], trans-golgi network integral membrane protein 2 [TGOLN2], sortilin [SORT1], desmoglein-2 [DSG2] and neuroblast differentiation-associated protein [AHNAK]) and 11 (serotransferrin [TF], inter-α-trypsin inhibitor heavy chain 4 [ITIH4], complement C3 [C3], transketolase [TKT], fibronectin [FN1], ubiquitin-like modifier-activating enzyme 1 [UBA1], cell division control protein 42 homolog [CDC42], glutathione s-transferase P1 [GSTP1], sodium/potassium-transporting ATPase subunit alpha-1 [ATP1A1], ADP-ribosylation factor 1 [ARF1] and pro-cathepsin H [CTSH]) proteins associated with high and low LVM regression, respectively. These proteins were functionally linked with insulin-like growth factor (IGF) transport and uptake regulation by IGF binding-proteins, platelet activation, signaling and aggregation and the immune system’s activity. The concentration of IGF-1 in urine samples was associated with low LVM regression after delivery. Conclusions Urine proteome reflects postpartum cardiac RR. Specifically, eight urine proteins (GSTP1, ARF1, FN1, SORT1, SIAE, GLA, ITIH4 and DGS2) show clinical value in identifying women at higher risk for incomplete postpartum RR. In addition, the association between IGF and postpartum LVM regression was validated.