Evidence of myocyte hyperplasia in hypertrophic cardiomyopathy and other disorders with myocardial hypertrophy?

Ferrans, Víctor J.; Rodriguez, Eugene

doi:10.1007/978-3-642-85369-2_4

Cited by 4 publications

(5 citation statements)

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“…between P3 and P4 in mice), and is the major physiological mechanism underlying the increase in total myocytes mass during the postnatal period [42] . It is also a relevant mechanism in various pathological models in which exaggerated hyperplasia, resulting from the cytokinesis of differentiated cardiomyocytes, contributes to hypertrophy [37] , [43] . Cardiomyocytes hyperplasia and proliferation have been described in a lethal neonatal familial form of dilated mitogenic cardiomyopathy [44] .…”

Section: Discussionmentioning

confidence: 99%

Trpm4 Gene Invalidation Leads to Cardiac Hypertrophy and Electrophysiological Alterations

et al. 2014

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RationaleTRPM4 is a non-selective Ca2+-activated cation channel expressed in the heart, particularly in the atria or conduction tissue. Mutations in the Trpm4 gene were recently associated with several human conduction disorders such as Brugada syndrome. TRPM4 channel has also been implicated at the ventricular level, in inotropism or in arrhythmia genesis due to stresses such as ß-adrenergic stimulation, ischemia-reperfusion, and hypoxia re-oxygenation. However, the physiological role of the TRPM4 channel in the healthy heart remains unclear.ObjectivesWe aimed to investigate the role of the TRPM4 channel on whole cardiac function with a Trpm4 gene knock-out mouse (Trpm4 -/-) model.Methods and ResultsMorpho-functional analysis revealed left ventricular (LV) eccentric hypertrophy in Trpm4 -/- mice, with an increase in both wall thickness and chamber size in the adult mouse (aged 32 weeks) when compared to Trpm4+/+ littermate controls. Immunofluorescence on frozen heart cryosections and qPCR analysis showed no fibrosis or cellular hypertrophy. Instead, cardiomyocytes in Trpm4-/- mice were smaller than Trpm4+/+with a higher density. Immunofluorescent labeling for phospho-histone H3, a mitosis marker, showed that the number of mitotic myocytes was increased 3-fold in the Trpm4-/-neonatal stage, suggesting hyperplasia. Adult Trpm4 -/- mice presented multilevel conduction blocks, as attested by PR and QRS lengthening in surface ECGs and confirmed by intracardiac exploration. Trpm4-/-mice also exhibited Luciani-Wenckebach atrioventricular blocks, which were reduced following atropine infusion, suggesting paroxysmal parasympathetic overdrive. In addition, Trpm4 -/- mice exhibited shorter action potentials in atrial cells. This shortening was unrelated to modifications of the voltage-gated Ca2+ or K+ currents involved in the repolarizing phase.ConclusionsTRPM4 has pleiotropic roles in the heart, including the regulation of conduction and cellular electrical activity which impact heart development.

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Section: Discussionmentioning

confidence: 99%

Trpm4 Gene Invalidation Leads to Cardiac Hypertrophy and Electrophysiological Alterations

et al. 2014

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“…The failure of the adult mammalian myocardium to reactivate the cell cycle has been postulated to be a primary limiting factor in restoring function to the damaged heart. Thus, although limited induction of DNA synthesis in the heart as a response to stress or other factors has been described (29,70), there is little evidence for cytoplasmic division or cytokinesis in mammals. In contrast, cardiomyocytes from lower vertebrates are capable of dividing postnatally (158,167).…”

Section: Introductionmentioning

confidence: 99%

Cardiac Myocyte Cell Cycle Control in Development, Disease, and Regeneration

Ahuja

Sdek²,

MacLellan

2007

Physiological Reviews

507

475

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Cardiac myocytes rapidly proliferate during fetal life but exit the cell cycle soon after birth in mammals. Although the extent to which adult cardiac myocytes are capable of cell cycle reentry is controversial and species-specific differences may exist, it appears that for the vast majority of adult cardiac myocytes the predominant form of growth postnatally is an increase in cell size (hypertrophy) not number. Unfortunately, this limits the ability of the heart to restore function after any significant injury. Interest in novel regenerative therapies has led to the accumulation of much information on the mechanisms that regulate the rapid proliferation of cardiac myocytes in utero, their cell cycle exit in the perinatal period, and the permanent arrest (terminal differentiation) in adult myocytes. The recent identification of cardiac progenitor cells capable of giving rise to cardiac myocyte-like cells has challenged the dogma that the heart is a terminally differentiated organ and opened new prospects for cardiac regeneration. In this review, we summarize the current understanding of cardiomyocyte cell cycle control in normal development and disease. In addition, we also discuss the potential usefulness of cardiomyocyte self-renewal as well as feasibility of therapeutic manipulation of the cardiac myocyte cell cycle for cardiac regeneration.

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“…5,6 Limited induction of DNA synthesis in the heart has been described in response to various stimuli. 7,8 Yet, there has been little evidence for cytoplasmic division or cytokinesis in mammals. In contrast to cardiomyocytes from lower vertebrates, which are well endowed to divide postnatally, 9,10 proliferation ceases in the perinatal mammalian heart in conjunction with the downregulation of cyclin-dependent kinase (cdk) activities.…”

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confidence: 99%