Transcriptome changes in cardiomyocytes isolated from a rat model of progressive heart failure

Heart failure is among the leading causes of death globally. Ventricular failure progresses through a hypertrophic compensatory phase followed by failure of the ventricle function through rapid decompensation. In order to unravel right heart specific mechanisms of disease, rat animal models were established that (i) reflect the slowly progressive mode of compensation / decompensation and (ii) allow comparative analyses of left versus right heart failure in the same experimental set up. Non-restrictive clips around the pulmonary artery (pulmonary artery banding, PAB) or the aorta (aortic banding, AOB) were surgically implanted into weanling rats. Upon animal growth the clips become increasingly constrictive, leading to a compensatory, hypertrophic state at around 6 weeks and heart failure at 21 (PAB) or 24 weeks (AOB). Disease progression was monitored functionally and by sonography. Differential gene expression analysis was performed for all three treatment groups (sham, AOB, PAB), at both time points (compensation, decompensation) and for both ventricles. Overall design: From both phases of AOB and PAB, as well as from matching sham-operated animals, cardiomyocytes (CM) were isolated from the left ventricle and from the right ventricle and total RNA was extracted . Then, total RNAseq was performed after depletion of ribosomal RNAs. A total of 41 animals were included in this study.