Fingerprint profile of alcohol-associated heart failure in human hearts

Georges E. Haddad; Lori Saunders; Maria Carles; Seth D. Crosby; Federica Del Monte; Thomas E. Macgillivray; Marc J. Semigran; G. William Dec; Roger J. Hajjar; Angelia A. Doye; Rita Glass; Margo El; Judith K. Gwathmey

doi:10.1111/j.1530-0277.2008.00628.x

Fingerprint profile of alcohol-associated heart failure in human hearts

Georges E. Haddad, Lori Saunders, Maria Carles, Seth D. Crosby, Federica Del Monte, Thomas E. Macgillivray, Marc J. Semigran, G. William Dec, Roger J. Hajjar, Angelia A. Doye, Rita Glass, Margo El, Judith K. Gwathmey

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	814-821
Number of pages	8
Journal	Alcoholism: Clinical and Experimental Research
Volume	32
Issue number	5
DOIs	https://doi.org/10.1111/j.1530-0277.2008.00628.x
State	Published - May 2008

Keywords

Alcohol
Genes
Heart Failure
Microarray

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Haddad, G. E., Saunders, L., Carles, M., Crosby, S. D., Del Monte, F., Macgillivray, T. E., Semigran, M. J., Dec, G. W., Hajjar, R. J., Doye, A. A., Glass, R., El, M., & Gwathmey, J. K. (2008). Fingerprint profile of alcohol-associated heart failure in human hearts. Alcoholism: Clinical and Experimental Research, 32(5), 814-821. https://doi.org/10.1111/j.1530-0277.2008.00628.x

@article{0d24324e14f64aa99c08f4249c0880fb,

title = "Fingerprint profile of alcohol-associated heart failure in human hearts",

abstract = "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.",

keywords = "Alcohol, Genes, Heart Failure, Microarray",

author = "Haddad, {Georges E.} and Lori Saunders and Maria Carles and Crosby, {Seth D.} and {Del Monte}, Federica and Macgillivray, {Thomas E.} and Semigran, {Marc J.} and Dec, {G. William} and Hajjar, {Roger J.} and Doye, {Angelia A.} and Rita Glass and Margo El and Gwathmey, {Judith K.}",

year = "2008",

month = may,

doi = "10.1111/j.1530-0277.2008.00628.x",

language = "English",

volume = "32",

pages = "814--821",

journal = "Alcoholism: Clinical and Experimental Research",

issn = "0145-6008",

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T1 - Fingerprint profile of alcohol-associated heart failure in human hearts

AU - Haddad, Georges E.

AU - Saunders, Lori

AU - Carles, Maria

AU - Crosby, Seth D.

AU - Del Monte, Federica

AU - Macgillivray, Thomas E.

AU - Semigran, Marc J.

AU - Dec, G. William

AU - Hajjar, Roger J.

AU - Doye, Angelia A.

AU - Glass, Rita

AU - El, Margo

AU - Gwathmey, Judith K.

PY - 2008/5

Y1 - 2008/5

N2 - 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.

AB - 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.

KW - Alcohol

KW - Genes

KW - Heart Failure

KW - Microarray

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U2 - 10.1111/j.1530-0277.2008.00628.x

DO - 10.1111/j.1530-0277.2008.00628.x

M3 - Article

C2 - 18336640

AN - SCOPUS:42549095469

SN - 0145-6008

VL - 32

SP - 814

EP - 821

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

IS - 5

ER -

Fingerprint profile of alcohol-associated heart failure in human hearts

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Keywords

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