Apoptosis and Post-infarction Left Ventricular Remodeling

Baldi, Alfonso; Abbate, Antonio; Bussani, Rossana; Patti, Giuseppe; Melfi, Rosetta; Angelini, Anna; Dobrina, Aldo; Rossiello, Raffaele; Silvestri, Furio; Baldi, Feliciano; Sciascio, Germano Di

doi:10.1006/jmcc.2001.1498

Cited by 158 publications

(122 citation statements)

References 29 publications

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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: 79%

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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Section: Discussionmentioning

confidence: 79%

The Effects of Nebivolol on Apoptosis in a Rat Infarct Model

Mercanoğlu

Safran

Güngör

et al. 2007

Circ J

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“…Sampling of the hearts was done in the peri-infarct regions as previously described. 6 Briefly, a gross pathological examination was used to define the infarct area, infarct extension, infarct related artery status, gross indices of cardiac remodelling (transverse and longitudinal diameters, left ventricular free wall thickness, transverse diameter to wall thickness ratio). The clinical characteristics of each patient were obtained from the case records.…”

Section: Pathologymentioning

confidence: 99%

“…[6][7][8] In particular, cells expressing markers of DNA synthesis (PCNA) and/or RNA splicing (SC-35) were excluded from cell counts to avoid false positive results, and assessment of sensitivity and specificity of the assays employed for TUNEL and caspase-3 was done using human lymph nodes, as described elsewhere. [6][7][8] As additional potential markers of ischaemia, we measured nuclear hypoxia induced factor a (HIF-1a) staining: first, we employed mouse antihuman HIF-1a IgG (IgG2v, Novus Biological, Littleton, Colorado, USA) at 1:100 dilution, according to the supplier's directions, using a dicothomic positive/negative result; second, we assessed bax cytoplasmic expression (in 12 cases), using a mouse monoclonal antihuman bax sc-7480 from Santa Cruz Biotechnology, Santa Cruz, California, USA, as previously described in detail. 6 Expression was graded as mild or intense, and a human lymph node was used as a control.…”

Section: Pathologymentioning

confidence: 99%

“…[6][7][8] As additional potential markers of ischaemia, we measured nuclear hypoxia induced factor a (HIF-1a) staining: first, we employed mouse antihuman HIF-1a IgG (IgG2v, Novus Biological, Littleton, Colorado, USA) at 1:100 dilution, according to the supplier's directions, using a dicothomic positive/negative result; second, we assessed bax cytoplasmic expression (in 12 cases), using a mouse monoclonal antihuman bax sc-7480 from Santa Cruz Biotechnology, Santa Cruz, California, USA, as previously described in detail. 6 Expression was graded as mild or intense, and a human lymph node was used as a control. 6 HIF-1a nuclear staining appears very shortly after the induction of hypoxia and disappears within 10 minutes of restoration of normal oxygen values.…”

Section: Pathologymentioning

confidence: 99%

“…6 Expression was graded as mild or intense, and a human lymph node was used as a control. 6 HIF-1a nuclear staining appears very shortly after the induction of hypoxia and disappears within 10 minutes of restoration of normal oxygen values. It therefore represents a tissue marker for hypoxia, 9 and bax is a central mediator in the mitochondrial, ischaemia induced, caspase-9 dependent apoptotic cascade.…”

Section: Pathologymentioning

confidence: 99%

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681 Cyclooxygenase-2 (COX-2) expression at site of recent myocardial infarction: friend or foe

Abbate

Biondi‐Zoccai

Santini

et al. 2003

European Journal of Heart Failure Supplements

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Background: Cyclo-oxygenase-2 (COX-2) is induced in cardiomyocytes only in response to stress, such as ischaemia. Objective: To assess COX-2 expression at the site of recent myocardial infarction. Methods: COX-2 expression was evaluated by specific immunostaining in cardiomyocytes from 23 subjects who died 10-60 days after acute myocardial infarction. The relation between COX-2 myocardial expression and apoptotic rate was investigated. Cardiomyocyte apoptotic rate was defined as the number of cells co-expressing in situ end labelling of DNA fragmentation (TUNEL) and immunostaining for activated caspase-3. Results: COX-2 expression was found in cardiomyocytes at the site of infarction in nine of 23 cases (39%). It was associated with fivefold higher apoptotic rates (median 17.9% (interquartile range 11.0-25.4%) v 3.7% (0.6-12.8%); p = 0.016), and apoptotic rate increased progressively from mild to intense COX-2 staining (p for trend 0.009). COX-2 expression co-localised with TUNEL nuclear staining in myocytes, and there was a high concordance between COX-2 and hypoxia induced factor 1-a staining (78%, p = 0.021) and between COX-2 and bax (83%, p = 0.014). Subjects showing myocardial COX-2 expression were more likely to have enlarged hearts (p = 0.050), and intense COX-2 staining was strictly associated with symptomatic heart failure (p = 0.035). Conclusions: COX-2 is expressed in cardiomyocytes in nearly 40% of cases at the site of recent acute myocardial infarction, even late after the index event. Its expression was associated with extremely high apoptotic rates. These findings suggest a potential cause-effect link between COX-2 expression and enhanced myocardial apoptosis in ischaemic cardiomyopathy.

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