PMID- 12039650
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 0928-4680 (Print)
IS  - 0928-4680 (Linking)
VI  - 8
IP  - 3
DP  - 2002 Jun
TI  - Early and persistent activation of myocardial apoptosis, bax and caspases: 
      insights into mechanisms of progression of heart failure.
PG  - 183-192
AB  - The aim of this study was to test the hypothesis that persistent myocardial 
      apoptosis contributes to progression of heart failure in a canine model of 
      pacing-induced cardiomyopathy. Dogs were paced at 250 beats per minute for 1 week 
      (n=9), 3 weeks (n=14) and 4 weeks (n=14) with normal dogs served as controls 
      (n=12). Myocardial apoptosis was assessed by multiple methods including DNA 
      fragmentation and in situ terminal deoxynucleotidyl transferase-mediated dUTP 
      nick end labeling (TUNEL) staining, bax and bcl-2 protein expression, and caspase 
      activity. Pacing produced a progressive increase in left ventricular (LV) end 
      diastolic pressure (LVEDP) and plasma norepinephrine levels with no significant 
      increase in LV mass. The number of apoptotic cells was markedly increased after 1 
      week of pacing and remained increased at 4 weeks of pacing with characteristic 
      DNA laddering. The increase in apoptosis was associated with bax protein 
      expression and caspase activation while there was no detectable changes in bcl-2 
      protein expression. The estimated total number of apoptotic cells correlated with 
      cardiac output and LVEDP (r=-0.69 and 0.59, respectively, P<0.001). Plasma 
      norepinephrine and bax protein expression correlated significantly with the 
      estimated total number of apoptotic myocytes (r=0.62 and 0.42, respectively, 
      P<0.01). In conclusion, an early and persistent activation of myocardial 
      apoptosis and pro-apoptotic factors is likely an important mechanism that 
      contributes to the progression of heart failure in canine pacing-induced 
      cardiomyopathy.
FAU - Moe, Gordon W
AU  - Moe GW
AD  - Department of Medicine, Division of Cardiology, St. Michael's Hospital, Terrence 
      Donnelly Heart Center, University of Toronto, 30 Bond Street, Ontario, M5B1W8, 
      Toronto, Canada
FAU - Naik, George
AU  - Naik G
FAU - Konig, Andrea
AU  - Konig A
FAU - Lu, Xiangru
AU  - Lu X
FAU - Feng, Qingping
AU  - Feng Q
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Pathophysiology
JT  - Pathophysiology : the official journal of the International Society for 
      Pathophysiology
JID - 9433813
EDAT- 2002/06/01 10:00
MHDA- 2002/06/01 10:01
CRDT- 2002/06/01 10:00
PHST- 2002/06/01 10:00 [pubmed]
PHST- 2002/06/01 10:01 [medline]
PHST- 2002/06/01 10:00 [entrez]
AID - S0928468002000081 [pii]
AID - 10.1016/s0928-4680(02)00008-1 [doi]
PST - ppublish
SO  - Pathophysiology. 2002 Jun;8(3):183-192. doi: 10.1016/s0928-4680(02)00008-1.