Fingerprint Profile of Alcohol-Associated Heart Failure in Human Hearts
| Autor: | Thomas E. MacGillivray, Seth D. Crosby, Georges E. Haddad, Margo El, Maria Carles, Marc J. Semigran, Roger J. Hajjar, Angelia A. Doye, G. William Dec, Judith K. Gwathmey, Lori Saunders, Federica del Monte, Rita Glass |
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| Rok vydání: | 2008 |
| Předmět: |
Cardiomyopathy
Dilated Male medicine.medical_specialty Microarray Heart disease Heart Ventricles Medicine (miscellaneous) Disease Toxicology Pathogenesis Internal medicine Idiopathic dilated cardiomyopathy Humans Medicine Oligonucleotide Array Sequence Analysis Heart Failure business.industry Gene Expression Profiling Dilated cardiomyopathy Middle Aged medicine.disease Alcohol-Induced Disorders Psychiatry and Mental health Heart failure Circulatory system Cardiology business |
| Zdroj: | Alcoholism: Clinical and Experimental Research. 32:814-821 |
| ISSN: | 1530-0277 0145-6008 |
| DOI: | 10.1111/j.1530-0277.2008.00628.x |
| Popis: | Background: Excessive alcohol consumption is recognized as a cause of left ventricular dysfunction and leads often to alcohol-induced heart failure. It is thought that 36% of all cases of dilated cardiomyopathy are due to excessive alcohol intake. In addition, since chronic alcohol-consumption is a social behavior that is not always clearly self-reported clinically, it has been difficult to diagnose alcohol-induced heart failure versus heart failure due to idiopathic dilated cardiomyopathy (IDCM). Interestingly, both diseases are associated with left ventricular dysfunction and congestive heart failure. Methods: We have created a human heart failure cDNA array for IDCM from nonfailing and failing human hearts. The array contains 1,143 heart specific oligonucleotide probes. This array was used to screen RNA samples from transplant recipients and organ donors with alcohol-related heart failure. Results: Our study shows that alcohol-induced heart failure has a “specific fingerprint” profile of de-regulated genes. This profile can differentiate patients with pure alcohol-induced heart failure from patients with heart failure from IDCM with alcohol as a complicating or contributing factor. Furthermore, the pattern of gene de-regulation suggests a pivotal role for changes in matrix, cytoskeletal, and structural proteins in the development of clinical heart failure resulting from excessive alcohol consumption. Conclusions: We report for the first time a genomic “fingerprint” profile of de-regulated genes associated with human alcohol-induced heart failure. We conclude that the pathogenesis of alcohol-induced heart failure in humans is likely related to changes in architectural (e.g. cytoskeletal), matrix, and/or structural proteins. The reversibility of the disease upon cessation of alcohol consumption makes this a likely pathogenetic mechanism. Nevertheless, there is a point at which extracellular as well as cellular changes result in irreversible heart failure. |
| Databáze: | OpenAIRE |
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