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A trial structural remodeling takes on a critical significance to the occurrence and maintenance of atrial fibrillation (AF). As revealed by recent data, insulin-like growth factor-1 receptor (IGF-1R) plays a certain role in tissue fibrosis. In this study, the mechanism of IGF-1R in atrial structural remodeling was examined based on in vivo and in vitro experiments. First, cluster analysis of AF hub genes was conducted, and then the molecular mechanism was proposed by which IGF-1R regulates myocardial fibrosis via the PI3K/Akt/FoxO3a pathway. Subsequently, the mentioned mechanism was verified in human cardiac fibroblasts (HCFs) and rats transduced with IGF-1 overexpression type 9 adeno-associated viruses. The results indicated that IGF-1R activation up-regulated collagen I protein expression and Akt phosphorylation in HCFs and rat atrium. The administration of LY294002 reversed the above phenomenon, improved the shortening of atrial effective refractory period, and reduced the increased incidence of AF and atrial fibrosis in rats. The transfection of FoxO3a siRNA reduced the anti-fibrotic effect of LY294002 in HCFs. The above data revealed that activation of IGF-1R takes on a vital significance to atrial structural remodeling by facilitating myocardial fibrosis and expediting the occurrence and maintenance of AF through the regulation of the PI3K/Akt/FoxO3a signaling pathway. Key words: atrial fibrillation, atrial structural remodeling, myocardial fibrosis, IGF-1R, PI3K/Akt/FoxO3a pathway, Introduction Atrial fibrillation (AF) refers to the most common rapid arrhythmia in the clinic and the incidence is increasing on a year-to-year basis (Khan et al. 2019). AF increases the [...]

The success of any work with isolated cardiomyocytes depends on the reproducibility of cell isolation, because the cells do not divide. To date, there is no suitable in vitro model to study human adult cardiac cell biology. Although embryonic stem cells and induced pluripotent stem cells are able to differentiate into cardiomyocytes in vitro, the efficiency of this process is low. Isolation and expansion of human cardiomyocyte progenitor cells from cardiac surgical waste or, alternatively, from fetal heart tissue is another option. However, to overcome various issues related to human tissue usage, especially ethical concerns, researchers use large- and small-animal models to study cardiac pathophysiology. A simple model to study the changes at the cellular level is cultures of cardiomyocytes. Although primary murine cardiomyocyte cultures have their own advantages and drawbacks, alternative strategies have been developed in the last two decades to minimise animal usage and interspecies differences. This review discusses the use of freshly isolated murine cardiomyocytes and cardiomyocyte alternatives for use in cardiac disease models and other related studies. Key words: cardiomyocytes, myocardial ischemia, perfusion, primary culture, cardiac cell lines, cardiac differentiation, cardiotoxicity. Le succes de toute experience realisee avec des cardiomyocytes isoles depend de la reproductibilite de l'isolement cellulaire car ces cellules ne se divisent pas. Jusqu'a present, il n'existe aucun modele in vitro convenable qui permette d'etudier la biologie cellulaire de la cellule cardiaque adulte. Meme si les cellules souches embryonnaires et les cellules pluripotentes induites peuvent se differencier en cardiomyocytes in vitro, l'efficacite de ce processus est faible. L'isolement et la croissance des cellules souches humaines de cardiomyocytes a partir de dechets chirurgicaux ou de tissu cardiaque foetal constituent une autre option. Toutefois, afin de contourner les problemes de differents ordres relies a l'utilisation de tissu humain, notamment les preoccupations ethiques, les chercheurs utilisent des modeles animaux de grande ou de petite taille afin d'etudier la pathophysiologie cardiaque. Les cultures de cardiomyocytes constituent un modele simple permettant d'etudier les changements au niveau cellulaire. Meme si les cultures de cardiomyocytes de souris possedent leurs propres avantages et inconvenients, des strategies alternatives se sont developpees au cours des deux dernieres decennies afin de minimiser l'utilisation d'animaux et les differences inter-especes. Cet article de revue discute de l'utilisation des cardiomyocytes de souris frais et d'alternatives aux cardiomyocytes comme modeles de maladies cardiaques et d'autres maladies reliees. [Traduit par la Redaction] Mots-cles : cardiomyocytes, ischemie myocardique, perfusion, culture primaire, lignees cellulaires cardiaques, differenciation cardiaque, cardiotoxicite., Introduction The menace of cardiac diseases is rapidly increasing throughout the world. Recent scientific advances have helped in providing a greater understanding of the underlying causes of cardiac diseases. Various [...]

A defining feature of embryonic cardiomyocytes is their relatively high rates of proliferation. A gradual reduction in proliferative capacity throughout development culminates in permanent cell cycle exit by the vast majority of cardiomyocytes around the perinatal period. Accordingly, the adult heart has severely limited capacity for regeneration in response to injury or disease. The D-type cyclins (cyclin D1, D2, and D3) along with their catalytically active partners, the cyclin dependent kinases, are positive cell cycle regulators that play important roles in regulating proliferation of cardiomyocytes during normal heart development. While expression of D-type cyclins is generally low in the adult heart, expression levels are augmented in association with cardiac hypertrophy, but are uncoupled from myocyte cell division. Accordingly, re- activation of D-type cyclin expression in the adult heart has been implicated in pathophysiological processes via mechanisms distinct from those that drive proliferation during cardiac development. Growth factors and other exogenous agents regulate D- type cyclin production and activity in embryonic and adult cardiomyocytes. Understanding differences in the precise intracellular mediators downstream from these signalling molecules in embryonic versus adult cardiomyocytes could prove valuable for designing strategies to reactivate the cell cycle in cardiomyocytes in the setting of cardiovascular disease in the adult heart. Key words: D-type cyclins, heart development, hypertrophy, cell cycle, cardiovascular disease. Les cardiomyocytes embryonnaires se caracterisent par un taux de proliferation relativement eleve. Chez la majorite des cardiomyocytes, la reduction graduelle de leur capacite proliferative au cours du developpement culmine en une sortie permanente du cycle cellulaire autour de la periode perinatale. Consequemment, le coeur adulte possede une capacite extremement limitee de regeneration en reponse a un dommage ou une maladie. Les cyclines de type D (cycline D1, D2 et D3) et leurs partenaires actifs sur le plan catalytique, les kinases dependantes des cyclines, sont des regulateurs positifs du cycle cellulaire qui jouent un role important en regulant la proliferation des cardiomyocytes durant le developpement normal du coeur. Alors que l'expression des cyclines de type D est generalement faible dans le coeur adulte, leur niveau d'expression est augmente lors de l'hypertrophie cardiaque mais il n'est pas couple a la division des myocytes. Ainsi, la reactivation de l'expression des cyclines de type D dans le coeur adulte a ete impliquee dans des processus pathophysiologiques par l'intermediaire de mecanismes distincts de ceux qui controlent la proliferation lors du developpement cardiaque. Les facteurs de croissance et autres agents exogenes regulent la production et l'activite des cyclines de type D chez les cardiomyocytes embryonnaires et adultes. Il pourrait s' averer important de comprendre comment les cardiomyocytes embryonnaires et adultes different sur le plan des mediateurs intracellulaires precis qui agissent en aval de ces molecules de signalisation, afin d'elaborer des strategies pour reactiver le cycle cellulaire des cardiomyocytes lors de la maladie cardiovasculaire du coeur adulte. Mots-cles : cyclines de type D, developpement de coeur, hypertrophie, cycle cellulaire, maladie cardiovasculaire. [Traduit par la Redaction], Introduction During embryogenesis, the heart transforms from a simple tubular structure to a specialized 4-chambered pump. The morphological changes associated with heart formation are the result of the tightly controlled [...]