The integrative transcriptomic, proteomic and metabolomic profile of peripartum cardiomyopathy.

Abstract

Peripartum cardiomyopathy (PPCM) is a rare form of dilated cardiomyopathy that develops in late pregnancy or after delivery. It is of growing clinical and scientific interest, due to its increasing incidence, its potential severe clinical consequences that may include life-threatening acute heart failure that requires cardiac-intensive-care-unit/intensive-care-unit care and even cardiac transplantation and increasing appreciation of the previously underappreciated cardiac disease in women.

Due to its rarity, PPCM does not lend itself readily to investigation, and human tissue from biopsies is scarce. Subsequently, most published studies on PPCM use animal models. Biobanking as with the Sydney Heart Bank, the University of Sydney and multi-omics allows for investigation of this condition, with a higher density of samples available in the Bank and while using a comparably small amount of tissue as compared with traditional molecular methods.

This thesis aims to describe investigation of the mRNA transcriptomic, proteomic and metabolomic milieux of PPCM using human left ventricular tissue, as a first larger-scale study using human snap-frozen tissue. Bioinformatic analyses identify mRNAs, proteins and metabolites that suggest potential mechanisms by which this form of cardiomyopathy develops, perhaps as a secondary, environmental “hit” on the background of a first “hit” of genetic disposition, with this being an area for further research. However, the largely shared multi-omics profiles between PPCM and familial DCM suggest that PPCM is a subset of familial DCM. In spite of this, investigations into PPCM’s mechanisms and the differences may hold promise as potential, future diagnostic, prognostic and therapeutic targets.