Fingerprint profile of alcohol-associated heart failure in human hearts.
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.
Haddad
Georges E
GE
Department of Physiology & Biophysics, Howard University, Washington, DC, USA.
Saunders
Lori
L
Carles
Maria
M
Crosby
Seth D
SD
del Monte
Federica
F
Macgillivray
Thomas E
TE
Semigran
Marc J
MJ
Dec
G William
GW
Hajjar
Roger J
RJ
Doye
Angelia A
AA
Glass
Rita
R
El
Margo
M
Gwathmey
Judith K
JK
D020751:Alcohol-Induced Disorders / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis