Increased myocardial apoptosis in patients with unfavorable left ventricular remodeling and early symptomatic post-infarction heart failure

Abbate, Antonio; Biondi‐Zoccai, Giuseppe; Bussani, Rossana; Dobrina, Aldo; Camilot, Debora; Feroce, Florinda; Rossiello, Raffaele; Baldi, Feliciano; Silvestri, Furio; Biasucci, Luigi M.; Baldi, Alfonso

doi:10.1016/s0735-1097(02)02959-5

Cited by 178 publications

(134 citation statements)

References 37 publications

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“…The extent of apoptosis differs from patient to patient and is associated with the level of left ventricular remodeling following myocardial infarction. Abbate et al showed that the degree of left ventricular remodeling was directly associated with the extent of apoptosis in subjects who died shorty (10 days) after STEMI [1]. Moreover, the ex vivo measured apoptotic activity in human sera is higher in patients shorty after an MI and can predict survival in patients with heart failure [12].…”

Section: Discussionmentioning

confidence: 99%

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Prognostic value of TNF-Related Apoptosis Inducing Ligand (TRAIL) in acute coronary syndrome patients

Osmančík

Toušek

Teringová

et al. 2013

European Heart Journal

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Section: Discussionmentioning

confidence: 99%

“…Apoptosis plays an important role in the early development of heart failure and left ventricular remodeling in patients following myocardial infarction [1]. The extent of lost myocardium following acute myocardial infarction varies from patient to patient and depends on the degree of activity of apoptotic processes.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of TNF-Related Apoptosis Inducing Ligand (TRAIL) in acute coronary syndrome patients

Osmančík

Toušek

Teringová

et al. 2013

European Heart Journal

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“…Despite the relative resistance of cardiac myocytes to caspasedependent death, it is well established that apoptosis accounts for cardiac cell death during ischemia/reoxygenation (15,16), hypertension (17), and in maladaptive hypertrophy (18), although necrosis and autophagic cell death also play a relevant role (19). Interestingly, the space left by dead myocytes is filled by granulation tissue composed of several cell types, including macrophages, endothelial cells and fibroblasts (20), and newly synthesized extracellular matrix (ECM) (21,22), which is produced mainly by cardiac fibroblasts (23).…”

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confidence: 99%

Bcl-2 Is a Key Factor for Cardiac Fibroblast Resistance to Programmed Cell Death

Mayorga

Bahí

Ballester

et al. 2004

Journal of Biological Chemistry

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Cardiac fibroblasts play an essential role in the physiology of the heart. These produce extracellular matrix proteins and synthesize angiogenic and cardioprotective factors. Although fibroblasts of cardiac origin are known to be resistant to apoptosis and to remain metabolically active in situations compromising cell survival, the underlying mechanisms are unknown. Here, we report that cardiac fibroblasts were more resistant than dermal or pulmonary fibroblasts to mitochondriadependent cell death. Cytochrome c release was blocked in cardiac fibroblasts but not in dermal fibroblasts treated with staurosporine, etoposide, serum deprivation, or simulated ischemia, precluding caspase-3 activation and DNA fragmentation. Resistance to apoptosis of cardiac fibroblasts correlated with the expression of the anti-apoptotic protein Bcl-2, whereas skin and lung fibroblasts did not express detectable levels of this protein. Bcl-x L, Bax, and Bak were expressed at similar levels in cardiac, dermal, and lung fibroblasts. In addition, the death of cardiac fibroblasts during hypoxia was not associated with the cleavage of Bid but rather with Bcl-2 disappearance, suggesting the requirement of the mitochondrial apoptotic machinery to execute death receptor-induced programmed cell death. Knockdown of bcl-2 expression by siRNA in cardiac fibroblasts increased their apoptotic response to staurosporine, serum, and glucose deprivation and to simulated ischemia. Moreover, dermal fibroblasts overexpressing Bcl-2 achieved a similar level of resistance to these stimuli as cardiac fibroblasts. Thus, our data demonstrate that Bcl-2 is an important effector of heart fibroblast resistance to apoptosis and highlight a probable mechanism for promoting survival advantage in fibroblasts of cardiac origin.

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“…Clinical observations also support this relationship. [35][36][37] In the nebivolol treated group, AI was found significantly lower than MI-control group both on day 2 and day 28 of MI. In this group, in addition to total AI, regional AI rates were also significantly lower than the MI-control group.…”

Section: Discussionmentioning

confidence: 84%

The Effects of Nebivolol on Apoptosis in a Rat Infarct Model

Mercanoğlu

Safran

Güngör

et al. 2007

Circ J

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fter myocardial infarction (MI), a series of structural changes (expansion and thinning of the infracted area) occur. 1,2 Although these changes help to maintain the cardiac function at the early phase of MI, when they are not controlled, it might lead to left ventricular (LV) dysfunction. 3 Cellular and molecular mechanisms contributing to the LV dysfunction are not fully understood, apoptosis, both in the infarct and healthy myocardium has been shown as an important role. 4,5 Nebivolol, a selective -blocker, 6 was shown to improve the ventricular function and hemodynamic parameters in patients with LV dysfunction. In addition to -blocker activity, nebivolol regulates the releasing nitric oxide (NO) by the activation of endothelial NO synthase (e-NOS) in endothelial cells. NO is related not only to the maintenance of healthy endothelial function, but also to apoptosis.In the present study our aim is to evaluate the NO mediated effects of nebivolol after MI in rats and the role of antiapoptotic mechanisms in this effect. Methods Animal Groups, Dose Selection and Study DurationAnimals were housed in a temperature-controlled animal facility with a 12-h light/dark cycle, with tap water and rodent chow ad libitum and handled in accordance with the Guide for the Care and the Use of Laboratory Animals published by the US National Institutes of Health. All experimental procedures were approved by the Institutional Animal Ethic Committee of Istanbul University Experimental Medical Research Institute.Twelve-week-old male Sprague Dawley rats, with a mean weight of 250-300 g, were divided in 3 groups of 12 each: sham operated control (sham-control), MI induced (MI-control) and nebivolol treated (MI-nebivolol).Nebivolol was administrated within 10 min of reperfusion at dose of 0.1 mg/kg iv and continued orally at dose of 2.0 mg/kg, by gastric gavage once daily for 28 days. The iv dose of nebivolol was selected as the minimum -blocker dose (absence of significant effect on blood pressure and heart rate (HR)), after a preliminary dose-response study, (using 0.1-0.5-1 mg/kg of nebivolol iv) according to Sacco et al (Fig 1). 7 The oral dose was selected according to Sanchez et al. 8 Hemodynamic effects of these 2 dose regimes were compared with metoprolol, a 1-selective adrenoreceptor antagonist (Tables 1,2).To evaluate the effects of nebivolol on the apoptosis both in acute and sub-acute period of MI, time intervals were selected as 2 days (for acute) and 28 days (for sub-acute) of Background In the present study, nitric oxide (NO) was investigated to see if it mediated effects of nebivolol on apoptosis in the rat myocardial infarction (MI) model. Methods and ResultsRats were divided into 3 groups: sham operated (sham-control), MI-induced (MI-control) and nebivolol treated (MI-nebivolol). The initial dose of nebivolol was administrated intravenously (iv) within 10 min of post-MI reperfusion and continued orally for 28 days. NO mediated effects of nebivolol were assessed either in the early (2 nd day) or sub-acute (28 th day) ...

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Increased myocardial apoptosis in patients with unfavorable left ventricular remodeling and early symptomatic post-infarction heart failure

Abstract: Our data show that in patients dying >or=10 days after AMI, myocardial apoptosis is strongly associated with and may be a major determinant of unfavorable LV remodeling and early symptomatic post-infarction HF.

Cited by 178 publications

References 37 publications

Prognostic value of TNF-Related Apoptosis Inducing Ligand (TRAIL) in acute coronary syndrome patients

Prognostic value of TNF-Related Apoptosis Inducing Ligand (TRAIL) in acute coronary syndrome patients

Bcl-2 Is a Key Factor for Cardiac Fibroblast Resistance to Programmed Cell Death

The Effects of Nebivolol on Apoptosis in a Rat Infarct Model

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