Cardiac sympathetic innervation network shapes the myocardium by locally controlling cardiomyocyte size through the cellular proteolytic machinery
| العنوان: | Cardiac sympathetic innervation network shapes the myocardium by locally controlling cardiomyocyte size through the cellular proteolytic machinery |
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| المؤلفون: | Francesco S. Pavone, Annalisa Angelini, Marco Mongillo, Stefania Rizzo, Leonardo Sacconi, V Prando, Andrea Armani, Irene Costantini, Anna Di Bona, Erica Lazzeri, Marny Fedrigo, Mauro Franzoso, Cristina Basso, Tania Zaglia, Michael Rubart, Nicola Pianca |
| المصدر: | Journal of physiology (Lond., Print) 597 (2019): 3639–3656. doi:10.1113/JP276200 info:cnr-pdr/source/autori:Pianca, Nicola; Di Bona, Anna; Lazzeri, Erica; Costantini, Irene; Franzoso, Mauro; Prando, Valentina; Armani, Andrea; Rizzo, Stefania; Fedrigo, Marny; Angelini, Annalisa; Basso, Cristina; Pavone, Francesco S.; Rubart, Michael; Sacconi, Leonardo; Zaglia, Tania; Mongillo, Marco/titolo:Cardiac sympathetic innervation network shapes the myocardium by locally controlling cardiomyocyte size through the cellular proteolytic machinery/doi:10.1113%2FJP276200/rivista:Journal of physiology (Lond., Print)/anno:2019/pagina_da:3639/pagina_a:3656/intervallo_pagine:3639–3656/volume:597 J Physiol |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Cardiac function curve, Inotrope, Chronotropic, Sympathetic Nervous System, Physiology, cardiomyocytes, Protein degradation, Article, Contractility, Mice, neuro-cardiac synapse, protein degradation, sympathetic neurons, β-adrenergic signaling, 03 medical and health sciences, 0302 clinical medicine, Heart Rate, Heart rate, Animals, Humans, Myocytes, Cardiac, Cells, Cultured, Neurons, Chemistry, Myocardium, Infant, Heart, Coculture Techniques, Cell biology, Mice, Inbred C57BL, Coupling (electronics), 030104 developmental biology, beta-adrenergic signaling, 030217 neurology & neurosurgery, Intracellular, Signal Transduction |
| الوصف: | Key points The heart is innervated by a dense sympathetic neuron network which, in the short term, controls chronotropy and inotropy and, in the long term, regulates cardiomyocyte size. Acute neurogenic control of heart rate is achieved locally through direct neuro-cardiac coupling at specific junctional sites (neuro-cardiac junctions). The ventricular sympathetic network topology is well-defined and characteristic for each mammalian species. In the present study, we used cell size regulation to determine whether long-term modulation of cardiac structure is achieved via direct sympatho-cardiac coupling. Local density of cardiac innervation correlated with cell size throughout the myocardial walls in all mammalian species analysed, including humans. The data obtained suggest that constitutive neurogenic control of cardiomyocyte trophism occurs through direct intercellular signalling at neuro-cardiac junctions. Abstract It is widely appreciated that sympathetic stimulation of the heart involves a sharp increase in beating rate and significant enhancement of contractility. We have previously shown that, in addition to these evident functions, sympathetic neurons (SNs) also provide trophic input to cardiomyocytes (CMs), regulating cell and organ size. More recently, we have demonstrated that cardiac neurons establish direct interactions with CMs, allowing neuro-cardiac communication to occur locally, with a 'quasi-synaptic' mechanism. Based on the evidence that cardiac SNs are unevenly distributed throughout the myocardial walls, we investigated the hypothesis that CM size distribution reflects the topology of neuronal density. In vitro analyses of SN/CM co-cultures, ex vivo confocal and multiphoton imaging in clarified hearts, and biochemical and molecular approaches were employed, in both rodent and human heart biopsies. In line with the trophic effect of SNs, and with local neuro-cardiac communication, CMs, directly contacted by SNs in co-cultures, were larger than the non-targeted ones. This property reflects the distribution of CM size throughout the ventricles of intact mouse heart, in which cells in the outer myocardial layers, which were contacted by more neuronal processes, were larger than those in the less innervated subendocardial region. Such differences disappeared upon genetic or pharmacological interference with the trophic SN/CM signalling axis. Remarkably, CM size followed the SN distribution pattern in other mammals, including humans. Our data suggest that both the acute and chronic influence of SNs on cardiac function and structure is enacted as a result of the establishment of specific intercellular neuro-cardiac junctions. |
| تدمد: | 1469-7793 0022-3751 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bb6600205f0f7969da5587d047e7b581Test https://doi.org/10.1113/jp276200Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bb6600205f0f7969da5587d047e7b581 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14697793 00223751 |
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