Title
Exercise capacity in chronic heart failure patients is related to active gene transcription in skeletal muscle and not apoptosis Exercise capacity in chronic heart failure patients is related to active gene transcription in skeletal muscle and not apoptosis
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Faculty of Medicine and Health Sciences
Publication type
article
Publication
London ,
Subject
Human medicine
Source (journal)
European journal of cardiovascular prevention and rehabilitation. - London
Volume/pages
16(2009) :3 , p. 325-332
ISSN
1741-8267
ISI
000267297500009
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Background Muscle wasting partly explains exercise intolerance in chronic heart failure (CHF) patients. Skeletal muscle loss may result from apoptosis, and exercise training has been suggested to halt this process. The terminal deoxynucleotidyl transferase end-labeling (TUNEL) technique is frequently used to show apoptosis, but lacks specificity. Methods and results Before and after 4 months exercise training, skeletal muscle biopsies of 16 CHF patients (59.4±2.2 years, 11 men, 50% ischemic etiology, ejection fraction 28.8±2.7%, 66.3±3.6% of predicted oxygen uptake) and eight sedentary controls were analyzed for apoptosis (TUNEL, including the stringent variant without proteinase K digestion, immunohistochemical analyses using antibodies against cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase, PARP, and active gene transcription (anti-splicing factor SC-35). The number of TUNEL-positive nuclei in CHF patients was comparable with controls (3.2±0.7 vs. 3.1±1.7/mm2, P=0.2) and was not related to exercise parameters. With the stringent TUNEL and both immunostaining techniques, apoptosis was not detected. Co-occurrence of TUNEL and of SC-35 splicing factor suggests that at least part of TUNEL-positive nuclei is undergoing active gene transcription and therefore is not apoptotic. The SC-35-positive area correlated with % of predicted oxygen uptake (r=0.6, P=0.02), Wattmax (r=0.7, P=0.005) and VE/VCO2 slope (r=-0.6, P=0.03). At baseline, SC-35 immunoreactive area was significantly larger than in controls (P=0.001), but after exercise training, the difference was minimized (P=0.07). Conclusion Skeletal muscle apoptosis in CHF patients could not be confirmed. Active gene transcription might stain false positive for apoptotic nuclei with TUNEL. The level of active gene transcription/splicing was related to exercise performance.
E-info
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000267297500009&DestLinkType=RelatedRecords&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000267297500009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000267297500009&DestLinkType=CitingArticles&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
Handle