Original contributionEvidence of apoptosis in alcoholic cardiomyopathy☆
Introduction
High-dose alcohol consumption has been related to the development of dilated cardiomyopathy in a lifetime cumulated dose-dependent manner [1], [2], [3]. Because of the widespread consumption of alcohol, alcoholic heart muscle disease is one of the most frequent causes of acquired nonischemic dilated cardiomyopathy in developed countries [4], affecting as many as 13% of excessive alcohol consumers [1]. Most cases remain asymptomatic for a long time, being detectable only by cardiac function studies, which evidence diastolic left ventricular dysfunction initially and systolic left ventricular dysfunction subsequently [5]. As the disease progresses, however, patients frequently present with overt congestive heart failure and dysrhythmias and have a high risk of facing sudden death [3], [4]. The disease progresses if heavy alcohol consumption is maintained but fortunately ameliorates on abstinence or controlled drinking [6].
The mechanisms of alcohol-induced myocardial damage are multifactorial, with disruption of membrane composition, disturbances in excitation-contraction coupling mechanisms as well as in energy and protein turnover, and changes in mechanisms of genetic control being the most frequently involved, often appearing synchronously [7], [8]. As a consequence, myocyte damage appears and cell loss with interstitial fibrosis occurs. This myocyte loss has long been attributed to necrosis. To date, no study has reported on myocyte apoptosis in alcoholic dilated cardiomyopathy. As described in other cardiomyopathies, however, myocyte apoptosis may play a role in the development of structural heart damage [9], [10], [11]. We therefore decided to test the hypothesis that apoptosis is involved in the pathogenesis of alcohol-induced heart disease. To discern whether ethanol consumption or the presence of structural heart muscle damage is related to apoptosis, we compared alcoholic and hypertensive subjects.
Section snippets
Patient and control subject selection
Over a 3-year period, we consecutively studied hearts from subjects who suffered brain death of either traumatic or cerebrovascular origin and had initially been considered suitable as organ donors by the transplant team of the Hospital Clinic of Barcelona. Of 104 hearts from donors younger than 70 years, 58 were not suitable for transplantation. Of these latter organs, 7 specimens from patients with heart disease (5 with arterial disease and 2 with valvular disease), 3 from individuals with
Clinical data
Table 1 shows the epidemiologic and clinical data of the patients and control subjects. The groups were similar in age, whereas sex distribution showed a predominance of men among the alcoholic patients and hypertensive patients as compared with the control subjects. Cerebrovascular disease was the main cause of death in the alcoholic patients and hypertensive patients, whereas cranial trauma was the major cause in the control subjects. The time from hospital admission to organ extraction was
Discussion
In the present study, we found an increase in myocardial apoptosis measured by detection of DNA fragmentation with the TUNEL assay and activation of apoptosis-regulating mechanisms (BAX and BCL-2) in organ donors with cardiomyopathy of either alcoholic or hypertensive origin. In alcoholic patients, apoptosis evaluated with the TUNEL assay did not depend on a donor's ethanol consumption but did on the presence of heart damage. However, we also observed data suggesting a specific role of alcohol
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2018, Free Radical Biology and MedicineCitation Excerpt :Previous study showed that ethanol-induced nitrative stress and cardiomyocytes apoptosis, which are mediated by angiotensin II interaction with AT1 and subsequently the PKC-β1-dependent NOX pathway [45]. Moreover, Fernández-Solà J et al. [6] found apoptosis increases in the human hearts of individuals with long-term alcoholism. Consistent with previous studies, we found that the induction of apoptosis in the hearts of ethanol-fed mice and cardiomyocytes exposed to ethanol, these injuries were inhibited by CYP2J2 overexpression and exogenous 11,12-EET administration.
Drugs of Abuse and Cardiotoxicity
2018, Comprehensive Toxicology: Third Edition
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This study was supported by research grants from Fondo de Investigaciones Sanitarias (98/0330, 02/533, and 02/535) and from Generalitat de Catalunya (CUR 2001/SGR-279).