Cardiomyocyte apoptosis is associated with increased wall stress in chronic failing left ventricle

Jiang, Lele; Huang, Yifei; Hunyor, Stephen N.; Remedios, Cristobal G. dos

doi:10.1016/s0195-668x(02)00655-3

Cited by 43 publications

(40 citation statements)

References 36 publications

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“…There are also many studies demonstrating TUNEL positivity in a small (approximately 0.3%) population of cells in murine CHF models (Jiang et al, 2003). In human samples, the percentage of TUNEL positivity can be higher (up to 2%) (Di Napoli et al, 2003;Hughes, 2003).…”

Section: Discussionmentioning

confidence: 99%

Poly(ADP-Ribose) Polymerase Promotes Cardiac Remodeling, Contractile Failure, and Translocation of Apoptosis-Inducing Factor in a Murine Experimental Model of Aortic Banding and Heart Failure

Xiao

Chen

Zsengellér

et al. 2004

J Pharmacol Exp Ther

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Oxidant stress-induced activation of poly(ADP-ribose) polymerase (PARP) plays a role in the pathogenesis of various cardiovascular diseases. We have now investigated the role of PARP in the process of cardiac remodeling and heart failure in a mouse model of heart failure induced by transverse aortic constriction (banding). The catalytic activity of PARP was inhibited by the potent isoindolinone-based PARP inhibitor INO-1001 or by PARP-1 genetic deficiency. PARP inhibition prevented the pressure overload-induced decrease in cardiac contractile function, despite the pressure gradient between both carotid arteries being comparable in the two experimental groups. The development of hypertrophy, the formation of collagen in the hearts, and the mitochondrial-to-nuclear translocation of the cell death factor apoptosis-inducing factor (AIF) were attenuated by PARP inhibition. The ability of the inhibitor to block the catalytic activity of PARP was confirmed by immunohistochemical detection of poly(ADP-ribose), the product of the enzyme in the heart. Plasma levels of INO-1001, as measured at the end of the experiments, were in the concentration range sufficient to block the oxidant-mediated activation of PARP in murine cardiac myocytes in vitro. Myocardial hypertrophy and AIF translocation was also reduced in PARP-1-deficient mice undergoing aortic banding, compared with their wild-type counterparts. Overall, the current results demonstrate the importance of poly(ADP-ribos)ylation in the pathogenesis of banding-induced heart failure.Poly(ADP-ribose) polymerase (PARP)-1, a monomeric enzyme present in eukaryotes, is the major isoform of an expanding family of poly(ADP-ribosyl)ating enzymes (for review, see Virá g and Szabó, 2002). The main isoform of the family, PARP-1, primarily functions as a DNA damage sensor in the nucleus. Upon binding to damaged DNA mainly through the second zinc finger domain, PARP-1 forms homodimers and catalyzes the cleavage of NAD ϩ into nicotinamide and ADP-ribose and uses the latter to synthesize branched nucleic acid-like polymers poly(ADP-ribose) covalently attached to nuclear acceptor proteins. The biological role of PARP-1 is complex and includes the regulation of DNA repair and maintenance of genomic integrity.PARP-1 has been implicated in a variety of pathophysiological processes. PARP is an energy-consuming enzyme, which transfers ADP ribose units to nuclear proteins. As a result of this process, the intracellular nicotinamide dinucleotide (oxidized) (NAD ϩ ) and ATP levels remarkably decrease, resulting in cell dysfunction and cell death via the necrotic route (for review, see Virá g and Szabó, 2002).PARP becomes activated in response to DNA single-strand breaks, which can develop as a response to free radical and oxidant cell injury. Oxidative and nitrosative stress triggers the activation of the nuclear enzyme PARP, which contributes to the pathogenesis of various cardiovascular diseases, including myocardial infarction and ischemia-reperfusion and heart failure (for review, s...

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Section: Discussionmentioning

confidence: 99%

Poly(ADP-Ribose) Polymerase Promotes Cardiac Remodeling, Contractile Failure, and Translocation of Apoptosis-Inducing Factor in a Murine Experimental Model of Aortic Banding and Heart Failure

Xiao

Chen

Zsengellér

et al. 2004

J Pharmacol Exp Ther

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“…It is known that the wall stress at the basal segment is higher than at the mid and apical segments because of the nonspherical ventricular geometry and the largest local radius of the LV curvature in the basal part of the septum. 22,23 The propensity to develop increased apoptosis, collagen formation, and subsequent fibrosis might be higher in segments with elevated wall stress, 23 which may partly explain the phenomenon of significantly lower strain values of patients with CA at the basal compared with the apical segments. However, the factor of unequal wall stress is similarly encountered in patients with FD and FA and even more exaggerated in HP, where this additionally leads to significant postsystolic deformation at the basal septum ( Figure 1).…”

Section: Potential Mechanisms Of the Longitudinal Strain Gradientmentioning

confidence: 99%

Effect of Combined Systolic and Diastolic Functional Parameter Assessment for Differentiation of Cardiac Amyloidosis From Other Causes of Concentric Left Ventricular Hypertrophy

Liú¹,

Niemann

et al. 2013

Circ: Cardiovascular Imaging

164

110

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Background-Differentiation of cardiac amyloidosis (CA) from other causes of concentric left ventricular hypertrophy remains a clinical challenge, especially in patients with preserved ejection fraction at the early disease stages. Methods and Results-Consecutive hypertrophic patients with CA, isolated arterial hypertension, Fabry disease, and Friedreich ataxia (n=25 per group) were investigated; 25 healthy volunteers served as a control group. Standard echocardiography was performed, and segmental longitudinal peak systolic strain (LSsys) in the septum was assessed by 2-dimensional speckle tracking imaging. Indices of left ventricular hypertrophy and ejection fraction were similar among all patient groups. Deceleration time of early filling was significantly lower in patients with CA (147±46 milliseconds) compared with those with isolated arterial hypertension, Fabry disease, or control subjects (all P<0.0125). Septal basal LSsys (−6±2%) was significantly lower in patients with CA compared with those with isolated arterial hypertension (−14±6%), Fabry disease (−12±5%), Friedreich ataxia (−16±2%), or control subjects (−17±3%; all P<0.001), whereas septal apical LSsys was similar among all patient groups and control subjects (all P>0.05). A data-driven cutoff value for the ratio of septal apical to basal LSsys ratio >2.1 differentiated CA from other causes of left ventricular hypertrophy (sensitivity, 88%; specificity, 85%; positive predictive value, 67%; negative predictive value, 96%). The prevalence of septal apical to basal LSsys ratio >2.1 plus deceleration time of early filling <200 milliseconds was 88% in CA but 0% in all other groups. Conclusions-A systolic septal longitudinal base-to-apex strain gradient (septal apical to basal LSsys ratio >2.1), combined with a shortened diastolic deceleration time of early filling (deceleration time of early filling <200 milliseconds), aids in differentiating CA from other causes of concentric left ventricular hypertrophy. (Circ Cardiovasc Imaging. 2013;6:1066-1072.)

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“…Jiang et al (4) showed a significant relationship between the rate of cardiomyocyte apoptosis, or its regulatory factors, and maladaptive left ventricular remodeling in failing sheep hearts (4). It is not clear if the apoptosis that occurs during myocardial remodeling and HF is a cause or a consequence of cardiac dysfunction.…”

Section: Cell Death Inflammation and Collagen Remodeling Apoptosismentioning

confidence: 99%

Remodeling in the ischemic heart: the stepwise progression for heart

Mill¹,

Stefanon

Santos

et al. 2011

Braz J Med Biol Res

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Coronary artery disease is the leading cause of death in the developed world and in developing countries. Acute mortality from acute myocardial infarction (MI) has decreased in the last decades. However, the incidence of heart failure (HF) in patients with healed infarcted areas is increasing. Therefore, HF prevention is a major challenge to the health system in order to reduce healthcare costs and to provide a better quality of life. Animal models of ischemia and infarction have been essential in providing precise information regarding cardiac remodeling. Several of these changes are maladaptive, and they progressively lead to ventricular dilatation and predispose to the development of arrhythmias, HF and death. These events depend on cell death due to necrosis and apoptosis and on activation of the inflammatory response soon after MI. Systemic and local neurohumoral activation has also been associated with maladaptive cardiac remodeling, predisposing to HF. In this review, we provide a timely description of the cardiovascular alterations that occur after MI at the cellular, neurohumoral and electrical level and discuss the repercussions of these alterations on electrical, mechanical and structural dysfunction of the heart. We also identify several areas where insufficient knowledge limits the adoption of better strategies to prevent HF development in chronically infarcted individuals.

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Cardiomyocyte apoptosis is associated with increased wall stress in chronic failing left ventricle

Abstract: Apoptosis of cardiomyocytes in chronic HF is associated with increased wall stress, which may be responsible for the activation of a Fas/FasL and caspase-8 interaction in the region of intercalated discs.

Cited by 43 publications

References 36 publications

Poly(ADP-Ribose) Polymerase Promotes Cardiac Remodeling, Contractile Failure, and Translocation of Apoptosis-Inducing Factor in a Murine Experimental Model of Aortic Banding and Heart Failure

Poly(ADP-Ribose) Polymerase Promotes Cardiac Remodeling, Contractile Failure, and Translocation of Apoptosis-Inducing Factor in a Murine Experimental Model of Aortic Banding and Heart Failure

Effect of Combined Systolic and Diastolic Functional Parameter Assessment for Differentiation of Cardiac Amyloidosis From Other Causes of Concentric Left Ventricular Hypertrophy

Remodeling in the ischemic heart: the stepwise progression for heart

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