title: Evidence of apoptosis in alcoholic cardiomyopathy.
abstract: Apoptosis is a mechanism of cell death implicated in the pathogenesis of alcohol-induced organ damage. Experimental studies have suggested alcohol-mediated apoptosis in the cardiac muscle, and there is evidence of skeletal muscle apoptosis in long-term high-dose alcohol consumers. The relation between skeletal and cardiac muscle damage in alcoholism led us to consider the pathogenic role of apoptosis in alcoholic dilated cardiomyopathy. We evaluated apoptosis in the hearts of individuals with long-term alcoholism (n = 19), of those with long-standing hypertension (n = 20), and of those with no known disease as control subjects (n = 7). Alcohol consumption measurement, heart function evaluation, and myocardial immunohistochemical and morphometric analysis were performed. Apoptosis was evaluated with deoxyribonucleotidyl transferase-mediated dUTP-biotin nick end-labeling assay, and BAX and BCL-2 expressions were used to detect induction of and protection from proapoptotic mechanisms, respectively. Hearts from patients with a history of alcoholism showed apoptotic indexes similar to those of organs from hypertensive donors. Subjects with structural heart damage of alcoholic or hypertensive origin showed higher apoptotic indexes in deoxyribonucleotidyl transferase-mediated dUTP-biotin nick end-labeling, BAX, and BCL-2 assays as compared with control subjects (P < .001 for all). Moreover, New York Heart Association class I alcoholic patients displayed higher BAX and BCL-2 expressions as compared with control subjects. We conclude that apoptosis is present to a similar degree in the heart muscle of high-dose alcohol consumers and long-standing hypertensive subjects and is related to structural damage. Proapoptotic mechanisms are activated in alcoholic patients without heart damage.
authors.affiliation: Department of Internal Medicine, Hospital Clinic, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), University of Barcelona, 08036 Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Fernández-Solà
authors.forename: Francesc
authors.initials: F
authors.lastname: Fatjó
authors.forename: Emilio
authors.initials: E
authors.lastname: Sacanella
authors.forename: Ramón
authors.initials: R
authors.lastname: Estruch
authors.forename: Xavier
authors.initials: X
authors.lastname: Bosch
authors.forename: Alvaro
authors.initials: A
authors.lastname: Urbano-Márquez
authors.forename: José-María
authors.initials: JM
authors.lastname: Nicolás
mesh_terms: D000437:Alcoholism / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis; D002310:Cardiomyopathy, Alcoholic / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein