Apoptosis of myocytes and proliferation markers as prognostic factors in end-stage dilated cardiomyopathy

Zorc, Marjeta; Vraspir-Porenta, Olga; Zorc-Pleskovič, Ruda; Radovanović, N; Petrovič, Daniel

doi:10.1016/s1054-8807(02)00134-5

Cited by 28 publications

(35 citation statements)

References 15 publications

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“…The expression of pCNA, proliferation associated nuclear antigen Ki-67, has been demonstrated in heart sections undergoing severe stress (23). Phosphorylation at Ser-10 of histone H3 is tightly correlated with chromosome condensation during both mitosis and meiosis (24).…”

Section: Figmentioning

confidence: 99%

“…As reported by Beltrami et al (25) stem cells may regenerate myocytes that have been lost by severe stress, then go into "overdrive" in response to significant myocyte loss. Myocyte proliferation may be a component of the growth reserve of the heart upon demand, and there is evidence that regeneration in myocytes may challenge the dogma that the heart is a post-mitotic organ (6,23). Furthermore, the ability of the heart to replace damaged myocardium and induce cell division during failure suggests that there is a continuous turnover of cells during the lifespan of the organism.…”

Section: Figmentioning

confidence: 99%

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Myocardial Cell Death and Regeneration during Progression of Cardiac Hypertrophy to Heart Failure

Sarkar¹,

Chawla‐Sarkar²,

Young³

et al. 2004

Journal of Biological Chemistry

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Cardiac hypertrophy and ensuing heart failure are among the most common causes of mortality worldwide, yet the triggering mechanisms for progression of hypertrophy to failure are not fully understood. Tissue homeostasis depends on proper relationships between cell proliferation, differentiation, and death and any imbalance between them results in compromised cardiac function. Recently, we developed a transgenic (Tg) mouse model that overexpress myotrophin (a 12-kDa protein that stimulates myocyte growth) in heart resulting in hypertrophy that progresses to heart failure. This provided us an appropriate model to study the disease process at any point from initiation of hypertrophy end-stage heart failure. We studied detailed apoptotic signaling and regenerative pathways and found that the Tg mouse heart undergoes myocyte loss and regeneration, but only at a late stage (during transition to heart failure). Several apoptotic genes were up-regulated in 9-month-old Tg hearts compared with age-matched wild type or 4-week-old Tg hearts. Cardiac cell death during heart failure involved activation of Fas, tumor necrosis factor-␣, and caspases 9, 8, and 3 and poly(ADP-ribose) polymerase cleavage. Tg mice with hypertrophy associated with compromised functionshowedsignificantup-regulationofcyclins,cyclindependent kinases (Cdks), and cell regeneration markers in myocytes. Furthermore, in human failing and nonfailing hearts, similar observations were documented including induction of active caspase 3 and Ki-67 proteins in dilated cardiomyopathic myocytes. Taken together, our data suggest that the stress of extensive myocardial damage from longstanding hypertrophy may cause myocytes to reenter the cell cycle. We demonstrate, for the first time in an animal model, that cell death and regeneration occur simultaneously in myocytes during end-stage heart failure, a phenomenon not observed at the onset of the disease process.

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Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Myocardial Cell Death and Regeneration during Progression of Cardiac Hypertrophy to Heart Failure

Sarkar¹,

Chawla‐Sarkar²,

Young³

et al. 2004

Journal of Biological Chemistry

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“…These studies demonstrated that during an AMI widespread apoptosis occurs and is evident only a few hours after the onset of AMI, prior to the appearance of necrosis [35]. In addition, apoptosis was not detected in the normal myocardium [35,38,39]. Previous studies also suggest the possibility that an increased apoptotic rate in AMI influences peripheral circulation.…”

Section: Discussionmentioning

confidence: 84%

The role of p53, bax, bcl2, and 8-OHdG in human acute myocardial infarction

et al. 2010

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Apoptosis is implicated in unfavorable remodeling of the left ventricle during acute myocardial infarction (AMI). Both DNA damage and p53 play important roles in regulating apoptosis. Expression patterns of apoptotic regulating genes such as p53, bax, and bcl-2 highlight the importance of inhibiting ventricle remodeling and subsequent injuries. In the present study, serum levels of p53 and 8-hydroxy-2-deoxyguanosine (8-OHdG) as well as p53, bax, and bcl-2 expression were examined after the onset of AMI in Iranian patients. Serum levels of p53 and 8-OHdG were measured by enzyme-linked immunosorbent assay (ELISA) and the presence of p53 protein and mRNA expression of p53, bax, and bcl-2 were analyzed by Western blotting and real time RT-PCR methods respectively. In patients presenting with AMI, serum levels of p53 and 8-OHdG were increased in comparison to healthy controls. Likewise, transcripts of p53 and bax were also elevated in patients while bcl-2 was decreased. Collectively, our data suggest the novel use of p53 and 8-OHdG as markers of apoptosis and DNA damage following AMI. Our results also revealed that apoptosis occurs in concert with an up-regulation of p53 and bax and a down-regulation of bcl-2 which may suggest a possible therapeutic intervention in patients recovering from AMI.© Versita Sp. z o.o.

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“…It is clear that further experiments (using biopsies obtained at different stages of heart failure) are required to clarify the relationship between apoptosis and PARP-1 activation. For example, such endocardial biopsies were taken and evaluated for apoptotic markers in the case of dilatative cardiomyopathy (40)(41)(42)(43)(44). Interestingly, controversial results were obtained, suggesting that the therapy of the patients or methodical difficulties (obtaining endocardial biopsies from the same locations) affect the results of the apoptotic tests.…”

Section: R E S E a R C H A R T I C L E M O L M Ementioning

confidence: 99%