Abstract 324: Analysis of Transcriptome Profiles Identifies Novel Genes in Pathological Cardiac Hypertrophy
Both the underlying cause and resulting consequence of many cardiovascular diseases is the permanent loss of contractile cardiac myocytes (CMs). Because the vertebrate heart has no innate ability to regenerate, the response to disease stimuli is limited to hypertrophy, an initial response to preserve cardiac function. However, sustained hypertrophy can turn the growth response of myocytes to one of cell death leading to pathological ventricular remodeling and decreased cardiac function. In this study, we are interested in identifying novel therapeutic gene targets that play a role in cardiac hypertrophic progression. To identify differentially expressed genes in hypertrophy, we utilized trans-aortic constriction (TAC) to induce hypertrophy in mice and performed whole transcriptome profiling on isolated CMs and compared to wild-type adult and embryonic CMs. Globally, the correlation coefficients between adult or TAC CM samples ranged from 0.955 to 0.991, suggesting limited early response of CMs in hearts subjected to TAC. However, pathway and ontology analysis revealed that embryonic CMs are far different from both adult and TAC in global gene expression profile. Through bioinformatic analysis, we identified a panel of 12 genes that are differentially expressed between TAC and adult CMs. Pathway and ontology analysis implicated the genes to participate in either oxidative stress pathways or cardiac remodeling processes. Selective validation of the gene panel revealed MMP23 to have increased expression in an in vitro model of HF and in patients with end-stage heart failure (HF) suggesting a previously undescribed link to human HF disease progression. Together, this work identifies individual genes that contribute to pathological hypertrophy and can serve as novel targets for HF interventional therapies.
- © 2013 by American Heart Association, Inc.