Abstract 20236: Differential Expression of Genes Associated With Cardiovascular Disease in Cardiac Allograft Vasculopathy

BACKGROUND: Cardiac allograft vasculopathy (CAV) accounts for significant mortality after heart transplant (HT). The identification of molecular pathways involved in CAV may provide targets for preventive therapies and development of risk markers. METHOD: Gene expression profiling and transcriptome analysis using Illumina HiSeq 2000, was performed in 23 HT recipients, 12 with ISHLT grade 3 CAV and 11 without CAV matched on age, gender, and HT duration. Fastqc, Tophat, Samtools, and CuffDiff were utilized for quality control of raw reads, mapping short reads to reference genomes and testing differential expression between healthy subjects and HT recipients. Ingenuity pathway analysis (IPA) was performed to identify molecular pathways demonstrating differential expression. RESULT: Mean age was 54.6yrs, mean duration of transplant 8.1yrs, 69% were men, and etiology of HT was ischemic in 47.8%. IPA analysis revealed abnormalities in the following pathways: disease and biological functions, molecular and cellular functions, catonical pathways and toxicity. When cardiovascular pathways were evaluated, CAV was associated with differential expression in genes involved in cardiac arteriopathy, inflammation, fibrosis, heart failure, and arrhythmia. (Table 1) Conclusion: Genes associated with inflammation, arteriopathy, fibrosis, heart failure, and arrhythmias are differentially expressed in CAV. Longitudinal evaluation is required to determine the relationship of these genes and pathways to risk and development of CAV and their response to specific therapies.