Pooled microarray expression analysis of failing left ventricles reveals extensive cellular-level dysregulation independent of age and sex

Abstract

Existing cardiovascular studies tend to suffer from small sample sizes and unaddressed confounders. Re-profiling of 9 microarray datasets revealed significant global gene expression differences between 358 failing and 191 non-failing left ventricles independent of age and sex (p = 5.1e-10). Covariate-adjusted mixed-effect regression revealed 17 % (945/5553) genes with >1.5-fold changes. The extracellular matrix and integral membrane ontologies were significantly enriched and depleted in failing ventricles, respectively. Furthermore, MTSS1 implicated in cardiovascular dysfunction showed the greatest change in ischemic compared to dilated cardiomyopathy (Bonferroni p < 0.05 for all genes and ontologies). Transcriptomic meta-profiling here provided deeper insight into heart failure at the cellular level.