Upregulation of Bcl-2 proteins during the transition to pressure overload-induced heart failure

Moorjani, Narain; Catarino, Pedro; Trabzuni, Danyah; Saleh, Soad; Moorji, Azadali; Dzimiri, Nduna; Al‐Mohanna, Futwan; Westaby, Stephen; Ahmad, Manzoor

doi:10.1016/j.ijcard.2006.04.037

Cited by 27 publications

(24 citation statements)

References 29 publications

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“…However, it reduced cardiomyocyte size, resulted in lower number of TUNEL-detected apoptotic cardiomyocytes and reduced the significantly elevated Bax to Bcl-2 ratio. An increased expression of pro-apoptotic Bax to anti-apoptotic Bcl-2, an index of apoptosis, has been reported in several animal models of heart failure (Dent et al 2007;Leri et al 1998;Moorjani et al 2007). In the present study, the expression of Bax was not significantly affected by moxonidine treatment in both age groups.…”

Section: Discussionmentioning

confidence: 98%

Functional and molecular effects of imidazoline receptor activation in heart failure

et al. 2011

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Section: Discussionmentioning

confidence: 98%

Functional and molecular effects of imidazoline receptor activation in heart failure

et al. 2011

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“…pressure overload; oxidative stress; apoptosis; mitochondrial function CHRONIC PRESSURE OVERLOAD results in cardiac remodeling, including hypertrophy, which can lead to heart failure (14,30,36,37). However, the underlying mechanisms in this cardiac remodeling process are poorly understood.…”

mentioning

confidence: 99%

“…Increase in this ratio leads to collapse of the mitochondrial membrane potential (1) and translocation of cytochrome c into the cytoplasm, triggering the caspase cascade and subsequent apoptotic cell death (32,39,40). Recently, Moorjani et al (30) reported an activation of caspase cascade and upregulation of Bcl-2 proteins during the transition to pressure overload-induced heart failure in a sheep model.…”

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confidence: 99%

Activation of apoptotic processes during transition from hypertrophy to heart failure in guinea pigs

Sharma

Dhingra²,

Khaper³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Changes in oxidative stress and apoptotic process were studied during the progression of a compensated hypertrophy to a decompensated heart failure in guinea pigs. Banding of the ascending aorta resulted in heart hypertrophy. At 10 wk, ventricle-to-body weight ratio and thickness of the interventricular septum as well as the left ventricular wall were increased significantly. Although fractional shortening and ejection fraction were decreased, there were no signs of heart failure. Furthermore, there was no increase in wet-to-dry weight ratios for the lungs and liver at this stage. However, at 20 wk, heart failure was characterized by a significant depression in heart function as indicated by a decrease in fractional shortening, and ejection fraction and a lesser increase in wall thickness from diastole to systole. Animals also showed clinical signs of heart failure, and the wet-to-dry weight ratios of the lungs and liver were significantly higher. Cardiomyocyte oxidative stress was significantly higher in the 20-wk aortic-banded group. The ratio of Bax to Bcl-xl showed an increase at 10 wk, and there was a further increase at 20 wk. Mitochondrial membrane potential in the aortic-banded animals was significantly decreased at 10 and 20 wk. Cytochrome c levels were higher in the cytosol compared with the mitochondria, leading to a considerable increase in the expression of p17 subunit of caspase-3. At 20 wk, both early and late stages of apoptosis were observed in isolated cardiomyocytes. It is suggested that an increase in oxidative stress initiates mitochondrial death pathway during the hypertrophic stage, leading to apoptosis and heart failure at a later stage.

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“…Such an increase of bcl2 has been observed earlier in sheep subjected to aortic banding, but this increase was accompanied by an increased bax/bcl2 ratio [24]. Nevertheless, Moorjani et al gradually increased the constriction in order to provoke LV dysfunction as soon as six weeks after operation [24]. A similar study depicts an increased and decreased expression of pro- and anti-apoptotic genes respectively after TAC as well [23].…”

Section: Discussionmentioning

confidence: 54%

“…This could explain the absence of measurable apoptosis in our setting. Such an increase of bcl2 has been observed earlier in sheep subjected to aortic banding, but this increase was accompanied by an increased bax/bcl2 ratio [24]. Nevertheless, Moorjani et al gradually increased the constriction in order to provoke LV dysfunction as soon as six weeks after operation [24].…”

Section: Discussionmentioning

confidence: 77%

Vascular Endothelium Derived Endothelin-1 Is Required for Normal Heart Function after Chronic Pressure Overload in Mice

et al. 2014

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BackgroundEndothelin-1 participates in the pathophysiology of heart failure. The reasons for the lack of beneficial effect of endothelin antagonists in heart failure patients remain however speculative. The anti-apoptotic properties of ET-1 on cardiomyocytes could be a reasonable explanation. We therefore hypothesized that blocking the pro-apoptotic TNF-α pathway using pentoxifylline could prevent the deleterious effect of the lack of ET-1 in a model for heart failure.MethodsWe performed transaortic constriction (TAC) in vascular endothelial cells specific ET-1 deficient (VEETKO) and wild type (WT) mice (n = 5–9) and treated them with pentoxifylline for twelve weeks.ResultsTAC induced a cardiac hypertrophy in VEETKO and WT mice but a reduction of fractional shortening could be detected by echocardiography in VEETKO mice only. Cardiomyocyte diameter was significantly increased by TAC in VEETKO mice only. Pentoxifylline treatment prevented cardiac hypertrophy and reduction of fractional shortening in VEETKO mice but decreased fractional shortening in WT mice. Collagen deposition and number of apoptotic cells remained stable between the groups as did TNF-α, caspase-3 and caspase-8 messenger RNA expression levels. TAC surgery enhanced ANP, BNP and bcl2 expression. Pentoxifylline treatment reduced expression levels of BNP, bcl2 and bax.ConclusionsLack of endothelial ET-1 worsened the impact of TAC-induced pressure overload on cardiac function, indicating the crucial role of ET-1 for normal cardiac function under stress. Moreover, we put in light a TNF-α-independent beneficial effect of pentoxifylline in the VEETKO mice suggesting a therapeutic potential for pentoxifylline in a subpopulation of heart failure patients at higher risk.

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Upregulation of Bcl-2 proteins during the transition to pressure overload-induced heart failure

Cited by 27 publications

References 29 publications

Functional and molecular effects of imidazoline receptor activation in heart failure

Functional and molecular effects of imidazoline receptor activation in heart failure

Activation of apoptotic processes during transition from hypertrophy to heart failure in guinea pigs

Vascular Endothelium Derived Endothelin-1 Is Required for Normal Heart Function after Chronic Pressure Overload in Mice

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