Chronic alcohol abuse can lead to alcoholic cardiomyopathy, a form of dilated cardiomyopathy (DCM). In fact, alcohol use can be linked to 3 in 10 cases of DCM, which is clinically characterized by ventricular dilatation, wall thinning, and dysfunction of the myocardium leading to congestive heart failure and eventually death. Although there are diverse etiologies of DCM such as high blood pressure, myocardial infarction, and chronic alcohol use, the resulting phenotype is relatively uniform and largely independent of the initiating disease/injury. The goal of this study is to identify protein variations, and potential molecular mechanisms, associated with alcohol linked DCM. To do this RNA-extracted tissue samples will be obtained from a current gene expression study using human heart right ventricular biopsies obtained from patients diagnosed with DCM, specifically focusing on those with a history of alcohol use. These biopsies are retrieved at several time-points, from the same patient, over the course of treatment with the beta-blocker metoprolol. By simultaneously analyzing both the RNA and proteins that originate from the same initial patient sample, a more comprehensive disease profile will be obtained, and global changes in gene and protein expression between a single clinical patient over the course of drug treatment can be monitored.
Specific Aims : 1. Develop a quantitative strategy to identify and determine the absolute abundance of differentially expressed heart proteins in non-failing and failing explanted human heart samples. 2. Identify differentially expressed proteins in alcohol linked DCM heart patients prior to metoprolol treatment and at three and twelve months during the beta-blockade pharmacological regimen using quantitative proteomic methods. Relevance: These analyses will allow for the identification of differentially expressed proteins over the course of beta-blockade and will aid in discerning possible molecular mechanisms contributing to the improved phenotype observed in these patients. This knowledge may provide a clearer understanding of the mechanisms involved in alcoholic dilated cardiomyopathy and possibly lead to improved treatment options for DCM patients in the future ? ? ?
| Farias, Santiago E; Kline, Kelli G; Klepacki, Jacek et al. (2010) Quantitative improvements in peptide recovery at elevated chromatographic temperatures from microcapillary liquid chromatography-mass spectrometry analyses of brain using selected reaction monitoring. Anal Chem 82:3435-40 |
| Kline, Kelli G; Wu, Christine C (2009) MudPIT analysis: application to human heart tissue. Methods Mol Biol 528:281-93 |
| Kline, Kelli G; Finney, Greg L; Wu, Christine C (2009) Quantitative strategies to fuel the merger of discovery and hypothesis-driven shotgun proteomics. Brief Funct Genomic Proteomic 8:114-25 |
| Kline, Kelli G; Frewen, Barbara; Bristow, Michael R et al. (2008) High quality catalog of proteotypic peptides from human heart. J Proteome Res 7:5055-61 |
