Heart failure from the point of view of quantitative anatomy∗

Linzbach, A. J.

doi:10.1016/0002-9149(60)90084-9

Cited by 679 publications

(195 citation statements)

References 25 publications

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“…We formally tested the hypothesis that cardiomyocyte cell cycle activity contributes to postnatal cardiomyocyte proliferation by comparing the number of cardiomyocytes predicted to be generated by cell cycle events with the number present in the LV. Calculating the number of cardiomyocytes generated based on cell cycle activity requires input of the incidence of a cell cycle marker (1), the duration of its presence (2), and the probability that the marker indicates division (3). We used the percentage of cardiomyocytes in M-phase, which shows conservation of regulatory mechanisms and duration (∼1.5 h) between species, tissues, and ages (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

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Cardiomyocyte proliferation contributes to heart growth in young humans

Mollova¹,

Bersell

Walsh³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

647

578

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The human heart is believed to grow by enlargement but not proliferation of cardiomyocytes (heart muscle cells) during postnatal development. However, recent studies have shown that cardiomyocyte proliferation is a mechanism of cardiac growth and regeneration in animals. Combined with evidence for cardiomyocyte turnover in adult humans, this suggests that cardiomyocyte proliferation may play an unrecognized role during the period of developmental heart growth between birth and adolescence. We tested this hypothesis by examining the cellular growth mechanisms of the left ventricle on a set of healthy hearts from humans aged 0-59 y (n = 36). The percentages of cardiomyocytes in mitosis and cytokinesis were highest in infants, decreasing to low levels by 20 y. Although cardiomyocyte mitosis was detectable throughout life, cardiomyocyte cytokinesis was not evident after 20 y. Between the first year and 20 y of life, the number of cardiomyocytes in the left ventricle increased 3.4-fold, which was consistent with our predictions based on measured cardiomyocyte cell cycle activity. Our findings show that cardiomyocyte proliferation contributes to developmental heart growth in young humans. This suggests that children and adolescents may be able to regenerate myocardium, that abnormal cardiomyocyte proliferation may be involved in myocardial diseases that affect this population, and that these diseases might be treatable through stimulation of cardiomyocyte proliferation.heart failure | pediatrics H eart failure, a leading public health problem worldwide (1), is linked to the loss of cardiomyocytes (2-4). The only currently available, definitive therapy-heart transplantation-is limited by donor availability. New approaches, such as cell transplantation, have shown encouraging results in clinical trials (5, 6). However, a third, complementary strategy has emerged, based on stimulating endogenous regenerative mechanisms. One approach for developing such regeneration strategies is to examine the cellular mechanisms of myocardial growth, since mechanisms of regeneration should be similar to the mechanisms of development.Although stem and progenitor cells are important for morphogenesis of the myocardium, developmental growth in a number of nonhuman species is largely driven by cardiomyocyte proliferation (7-9). In biological models that, unlike adult humans, regenerate myocardium, cardiomyocyte proliferation is important for regeneration as well as postnatal heart growth (10, 11). For example, in mice, developmental cardiomyocyte proliferation continues for up to day 7 after birth, which coincides with the loss of regenerative capacity (11,12). The close temporal relationship between cardiomyocyte proliferation and heart regeneration in animals raises the question of whether and to what age and extent cardiomyocyte proliferation plays a role in humans. The answer may help us understand the endogenous regenerative potential of the human heart and possibly indicate strategies for stimulating cardiomyocyte proliferation to reg...

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Section: Discussionmentioning

confidence: 99%

“…heart failure | pediatrics H eart failure, a leading public health problem worldwide (1), is linked to the loss of cardiomyocytes (2)(3)(4). The only currently available, definitive therapy-heart transplantation-is limited by donor availability.…”

mentioning

confidence: 99%

Cardiomyocyte proliferation contributes to heart growth in young humans

Mollova¹,

Bersell

Walsh³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

647

578

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“…And third, in our study, the pressure overloadinduced hypertrophy was produced in adult, fully developed dogs, subjected to both short-and long-term pressure overload, whereas Archie et al (12), banded the pulmonary artery of 2-d-old lambs and subsequently studied the effects of the pressure overload 5-12 wk later. Whereas in the adult animal, the increase in right ventricular mass is thought to be primarily a result of an increase in cell size but not cell number (26,27), in the newborn, both hypertrophy and hyperplasia may account for the increase in ventricular mass.…”

Section: Methodsmentioning

confidence: 99%

Effects of exerimental right ventricular hypertrophy on myocardial blood flow in conscious dogs.

Murray¹,

Baig²,

Fishbein³

et al. 1979

J. Clin. Invest.

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A B S T R A C T The effects of right ventricular hypertrophy on the overall and regional distribution of myocardial blood flow in the absence of an elevated coronary arterial driving pressure were evaluated in 18 conscious dogs subjected to a chronic pressure overload of the right ventricle induced by pulmonary artery constriction. The sustained pressure overload for duration of4-6 wk or 4-5 mo resulted in significant increases in right ventricular mass (45 and 110%, respectively) and right ventricular fiber diameter (22 and 60%, respectively). Moreover, the presence *tmoderate and severe hypertrophy was associated with marked increases in transmural blood flow per gram to the right ventricle proportional to the observed increases in mass, i.e., of 36 and 109%, respectively, from a normal value of 0.67+0.04 ml/min per g, whereas left ventricular blood flow remained unaltered from a normal value of 1.00±0.06 ml/min per g. Despite the large increases in blood flow per gram to moderately and severely hypertrophied right ventricle, no significant changes in the ratio of capillary:muscle fiber number were observed. These data suggest that the development of right ventricular hypertrophy is characterized by a sustained compensatory response of the coronary circulation to the augmented work load and mass, and that it is not associated with a proliferative response of the vasculature supplying the enlarged ventricle.

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“…Cette endoréplication de l'ADN conduit-elle à des divisions non mitotiques? Oui, a répondu il y a longtemps Linzbach, sur la foi d'images un peu contestables d'éti-rements des myocytes [7]; mais comment démontrer, sur des pièces d'autopsie, que les divisions, si elles existent, se font sans mitose? Identifier des mitoses en activité sur ce type de matériel n'est déjà pas facile.…”

Section: La Capacité Des Myocytes Cardiaques à Proliférer Est Limitéeunclassified

Le myocyte cardiaque adulte peut-il encore proliférer ?

Swynghedauw

2004

Med Sci (Paris)

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La croissance et la prolifération postnatale sont des caractéristiques essentielles des myocytes cardiaques qui permettent au coeur d'adapter progressivement sa masse à la demande hémodynamique. Mais, une fois l'âge adulte atteint, l'arrêt des divisions semble être un mal nécessaire au maintien de la stabilité des fonctions électriques et mécaniques du myocarde. Les myocytes cardiaques ont-ils toutefois gardé la capacité de proliférer ? La question est, pour plusieurs raisons, loin d'être académique. Ainsi, en cas d'infarctus du myocarde, c'est-à-dire de mort par ischémie d'un certain nombre de cellules myocardiques, la capacité conservée des myocytes à proliférer permettrait d'envisager la régénération spontanée ou provoquée de la zone infarcie, en totalité ou en partie. En revanche, en cas d'incapacité des myocytes à proliférer, la fibrose réparatrice serait la seule possibilité de limiter les dégâts, et la transplantation d'un nouveau coeur, ou l'injection de cellules progénitrices, le seul moyen de rétablir la situation [1] (‹). La capacité des myocytes cardiaques à proliférer est limitéeEn milieu de gestation, la prolifération des cardiomyocytes est de 33%, contre 2% seulement à la naissance. Karyocinèse et cytocinèse sont dissociées après la naissance et, selon les espèces, il apparaît des cellules polynucléées, binucléées le plus souvent [2], ou polyploïdes [3]. L'arrêt du cycle cellulaire est sous le contrôle de deux familles fonctionnelles distinctes de protéines kinases inhibitrices dépendant des cyclines, Ink4 et Cip/Kip, lesquelles bloquent l'activation de l'ADN polymérase [2]; peu d'informations sont disponibles sur le fonctionnement de ces deux familles d'inhibiteurs au sein du myocarde jeune ou adulte [4]. L'hypothèse d'un arrêt du cycle cellulaire a également été renforcée par le fait que la survenue d'un cancer du myocarde est exceptionnelle et, en tous les cas, jamais MEDECINE/SCIENCES 2004 ; 20 : 710-4

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Heart failure from the point of view of quantitative anatomy∗

Cited by 679 publications

References 25 publications

Cardiomyocyte proliferation contributes to heart growth in young humans

Cardiomyocyte proliferation contributes to heart growth in young humans

Effects of exerimental right ventricular hypertrophy on myocardial blood flow in conscious dogs.

Le myocyte cardiaque adulte peut-il encore proliférer ?

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