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Therapeutic potential of c-Myc inhibition in the treatment of hypertrophic cardiomyopathy.

ABSTRACT: Investigating the pathophysiological importance of the molecular and mechanical development of cardiomyopathy is critical to find new and broader means of protection against this disease that is increasing in prevalence and impact. The current available treatment options for cardiomyopathy mainly focus on treating symptoms and strive to make the patient more comfortable while preventing progression of disease and sudden death. The proto-oncogene c-Myc (Myc) has been shown to be increased in many different types of heart disease, including hypertrophic cardiomyopathy, before any signs of the disease are present. As the mechanisms of action and multiple pathways of dependent actions of Myc are being dissected by many research groups, inhibition of Myc is becoming an attractive paradigm for prevention and treatment of cardiomyopathy and heart failure. Elucidating the role Myc plays in the development, propagation and perpetuation of cardiomyopathy and heart failure will one day translate into potential therapeutics for cardiomyopathy.

SUBMITTER: Wolfram JA

PROVIDER: S-EPMC3156459 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Therapeutic potential of c-Myc inhibition in the treatment of hypertrophic cardiomyopathy.

Wolfram Julie A JA Lesnefsky Edward J EJ Hoit Brian D BD Smith Mark A MA Lee Hyoung-Gon HG

Therapeutic advances in chronic disease 20110301 2

Investigating the pathophysiological importance of the molecular and mechanical development of cardiomyopathy is critical to find new and broader means of protection against this disease that is increasing in prevalence and impact. The current available treatment options for cardiomyopathy mainly focus on treating symptoms and strive to make the patient more comfortable while preventing progression of disease and sudden death. The proto-oncogene c-Myc (Myc) has been shown to be increased in many ...[more]

PMID: 21858245

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Project description:BackgroundCardiomyopathies are a heterogeneous group of heart diseases that can gradually cause severe heart failure. In particular, dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are the two main types of cardiomyopathies, yet the independent and communal biological mechanisms of both remain far from elucidated. Meanwhile, ferroptosis is a non-apoptotic form of cell death that has been proven to be associated with cardiomyopathies, but the concrete nature of the interaction remains unclear. Hence, this study explored the pathogenesis and ferroptosis mechanism of HCM and DCM via a bioinformatics analysis.MethodsSix datasets were downloaded from the Gene Expression Omnibus (GEO) database based on the study inclusion/exclusion criteria. After screening the differentially expressed genes (DEGs) and hub genes of HCM and DCM, subsequent analyses, including functional annotation, co-expression, validation, and transcription factors (TF)-mRNA-microRNA (miRNA) regulatory network construction, were performed. In addition, ferroptosis-related DEGs were also identified and verified in HCM and DCM.ResultsWe found 171 independent DEGs of HCM mainly enriched in the regulation of ERK1 and ERK2 cascade, while 171 independent DEGs of DCM were significantly involved in cell adhesion. Meanwhile, 32 communal DEGs (26 upregulated genes and 6 downregulated genes) and 3 hub genes [periostin (POSTN), insulin-like growth factor-binding protein-5 (IGFBP5), and fibromodulin (FMOD)] were determined to be shared between HCM and DCM and the functional annotation of these genes highlighted the important position of growth hormone in HCM and DCM. Moreover, we identified activating transcription factor 3 (ATF3), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and solute carrier family 1 member 5 (SLC1A5) as ferroptosis-related genes in HCM and STAT3 as a ferroptosis-related gene in DCM.ConclusionThe identified independent and communal DEGs contribute to uncover a potentially distinct and common mechanism of HCM and DCM and ferroptosis-related genes could provide us with a novel direction for exploration. In addition, 3 hub genes could be potential biomarkers or therapeutic targets in patients with cardiomyopathy.

Dataset Information

Therapeutic potential of c-Myc inhibition in the treatment of hypertrophic cardiomyopathy.

Publications

Therapeutic potential of c-Myc inhibition in the treatment of hypertrophic cardiomyopathy.

Similar Datasets

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