Serum proteomic analysis of peripartum cardiomyopathy reveals a unique disease with distinctive dysregulation of inflammatory and cholesterol metabolism pathways

Abstract Background: The pathophysiology of peripartum cardiomyopathy (PPCM) and its defining features when compared to other forms of cardiomyopathy remain unclear, thus limiting the development of targeted therapies. Methods: To address this knowledge gap, we utilized a systems biology approach and performed high-throughput aptamer-based proteomic analysis (SOMAscan 7K) of serum samples from women with PPCM (n = 67) or non-peripartum cardiomyopathy (NPCM, n = 31), and age-matched peripartum and non-peripartum healthy women (n = 10 each). Samples were obtained from the Investigation in Pregnancy-Associated Cardiomyopathy and the Intervention in Myocarditis and Acute Cardiomyopathy studies. Comparative analyses were performed based on the presence of cardiomyopathy and peripartum status. Results: Principal component analysis revealed distinct proteomic signatures of PPCM, NPCM, and each healthy control group (p<0.00001 for all pairwise comparisons). Comparative analyses of PPCM and NPCM identified hundreds of differentially expressed serum proteins before and after normalization to healthy controls. Pathway enrichment analyses of proteins differentially expressed in PPCM highlighted dysregulation of several biological pathways related to inflammation and cholesterol metabolism, including upregulation of the anti-inflammatory liver-X receptor/retinoid X receptor (LXR/RXR) pathway. Conclusions: Serum proteomic profiling of PPCM indicates that PPCM is a unique disease entity characterized by the dysregulation of pro-inflammatory and cholesterol metabolism-related anti-inflammatory pathways. These pathways may represent potential novel therapeutic targets in PPCM.