title: Evaluation of myocyte proliferation in alcoholic cardiomyopathy: telomerase enzyme activity (TERT) compared with Ki-67 expression.
abstract: OBJECTIVE
  Although the human heart was classically considered a terminal organ, recent studies have reported a myocyte proliferation response versus some aggressions. Excessive ethanol consumption induces development of cardiomyopathy (CMP) through myocyte apoptosis. We evaluated myocyte proliferation response in the heart of chronic alcoholic donors with telomerase activity (telomerase reverse transcriptase (TERT)) compared with Ki-67 nuclear expression.
  
  
  METHODS
  Heart samples were prospectively obtained from organ donors on life support. We included donors with (1) high lifetime alcohol consumption (n = 15), (2) longstanding hypertension (n = 14), (3) other causes of CMP (valve, coronary or idiopathic) (n = 8) and (4) previously healthy donors (n = 6). Groups 2 and 3 were subdivided according to the presence of CMP. Evaluation comprised parameters of ethanol consumption, left ventricular function by chest X-ray and 2D echocardiography, and histology and immunohistochemical studies. Myocyte proliferation was evaluated using an assay for Ki-67 expression and measuring telomerase gene activity by real-time PCR.
  
  
  RESULTS
  Forty-three donors were included in the study, 35 having CMP. Nuclear Ki-67 activity was low in healthy controls and significantly increased in the other groups, mainly in those with CMP. Alcoholics with CMP had a non-significantly lower proliferation response than the other CMP groups. No proliferation activity was detected with TERT in any case.
  
  
  CONCLUSIONS
  Heart Ki-67 proliferation activity increases in organ donors with CMP, independently of its origin. Alcoholics presented non-significant lower myocyte proliferation capacity compared with the other groups of CMP. TERT activity was not a useful marker of proliferation in this model. Ki-67 is a better procedure to evaluate proliferation than TERT expression in alcohol-induced heart damage.
authors: Alcohol Research Unit, Department of Internal Medicine, Institut d'Investigació August Pi i Sunyer, Hospital Clínic, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain.
authors: Meritxell
authors: M
authors: Lluís
authors: Joaquim
authors: J
authors: Fernández-Solà
authors: Sergi
authors: S
authors: Castellví-Bel
authors: Emilio
authors: E
authors: Sacanella
authors: Ramón
authors: R
authors: Estruch
authors: Alvaro
authors: A
authors: Urbano-Márquez
mesh_terms: D000328:Adult; D000368:Aged; D057229:Alcoholics; D017209:Apoptosis; D002310:Cardiomyopathy, Alcoholic / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006331:Heart Diseases / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000473:pathology; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014019:Tissue Donors
chemical_list: D002492:Central Nervous System Depressants; D019394:Ki-67 Antigen; D000431:Ethanol; D019098:Telomerase