Beyond cardiomyocytes: Cellular diversity in the heart's response to exercise

Trager, Lena; Lyons, Marion; Кузнецов, А С; Sheffield, Cedric; Roh, Kangsan; Freeman, Rebecca; Rhee, James; Guseh, James S.; Li, Haobo; Rosenzweig, Anthony

doi:10.1016/j.jshs.2022.12.011

Cited by 12 publications

(4 citation statements)

References 157 publications

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“…The present cell culture mimic of acute exercise studies the intrinsic response of the isolated cardiomyocyte to that mimic. However, the current protocols exclude extracellular regulation and influence of mechanical loading from the normal in vivo environment in the heart, 51 , 52 as well as contributions of other cell types, 53 all of which also contribute to in vivo exercise responses. In practice, this leads to profound perturbation to electrical and mechanical stability, which means that electrical stimulation frequencies differ from physiologic heart rates (in vitro 3 Hz‐180 beats/min vs. in vivo >5 Hz‐300beats/min) and contractions are unloaded with no external mechanical stress.…”

Section: Discussionmentioning

confidence: 99%

Electrically stimulated in vitro heart cell mimic of acute exercise reveals novel immediate cellular responses to exercise: Reduced contractility and metabolism, but maintained calcium cycling and increased myofilament calcium sensitivity

Costa,

Ghouri,

Johnston

et al. 2023

Cell Biochemistry & Function

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Cardiac cellular responses to acute exercise remain undescribed. We present a model for mimicking acute aerobic endurance exercise to freshly isolated cardiomyocytes by evoking exercise‐like contractions over prolonged periods of time with trains of electrical twitch stimulations. We then investigated immediate contractile, Ca2+, and metabolic responses to acute exercise in perfused freshly isolated left ventricular rat cardiomyocytes, after a matrix‐design optimized protocol and induced a mimic for acute aerobic endurance exercise by trains of prolonged field twitch stimulations. Acute exercise decreased cardiomyocyte fractional shortening 50%–80% (p < .01). This was not explained by changes to intracellular Ca2+ handling (p > .05); rather, we observed a weak insignificant Ca2+ transient increase (p = .11), while myofilament Ca2+ sensitivity increased 20%–70% (p < .05). Acidic pH 6.8 decreased fractional shortening 20%–70% (p < .05) because of 20%–30% decreased Ca2+ transients (p < .05), but no difference occurred between control and acute exercise (p > .05). Addition of 1 or 10 mM La− increased fractional shortening in control (1 mM La−: no difference, p > .05; 10 mM La−: 20%–30%, p < .05) and acute exercise (1 mM La−: 40%–90%, p < .01; 10 mM La−: 50%–100%, p < .01) and rendered acute exercise indifferent from control (p > .05). Intrinsic autofluorescence showed a resting NADstate of 0.59 ± 0.04 and FADstate of 0.17 ± 0.03, while acute exercise decreased NADH/FAD ratio 8% (p < .01), indicating intracellular oxidation. In conclusion, we show a novel approach for studying immediate acute cardiomyocyte responses to aerobic endurance exercise. We find that acute exercise in cardiomyocytes decreases contraction, but Ca2+ handling and myofilament Ca2+ sensitivity compensate for this, while acidosis and reduced energy substrate and mitochondrial ATP generation explain this.

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Section: Discussionmentioning

confidence: 99%

Electrically stimulated in vitro heart cell mimic of acute exercise reveals novel immediate cellular responses to exercise: Reduced contractility and metabolism, but maintained calcium cycling and increased myofilament calcium sensitivity

Costa,

Ghouri,

Johnston

et al. 2023

Cell Biochemistry & Function

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show abstract

“…Cardiomyocytes constitute approximately 75% of the total volume of the adult mammalian heart but only approximately 25%–35% of its total number of cells ( Trager et al, 2023 ). The proportion of nonparenchymal cells in the heart exceeds the number of cardiomyocytes; approximately half of the cells are fibroblasts, and one-fourth are endothelial cells (EC) ( Litviňuková et al, 2020 ).…”

Section: The Extracellular Microenvironment Of Cardiomyocytes Favors ...mentioning

confidence: 99%

Effects and mechanisms of the myocardial microenvironment on cardiomyocyte proliferation and regeneration

Zheng,

Hao,

Xia

et al. 2024

Front. Cell Dev. Biol.

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The adult mammalian cardiomyocyte has a limited capacity for self-renewal, which leads to the irreversible heart dysfunction and poses a significant threat to myocardial infarction patients. In the past decades, research efforts have been predominantly concentrated on the cardiomyocyte proliferation and heart regeneration. However, the heart is a complex organ that comprises not only cardiomyocytes but also numerous noncardiomyocyte cells, all playing integral roles in maintaining cardiac function. In addition, cardiomyocytes are exposed to a dynamically changing physical environment that includes oxygen saturation and mechanical forces. Recently, a growing number of studies on myocardial microenvironment in cardiomyocyte proliferation and heart regeneration is ongoing. In this review, we provide an overview of recent advances in myocardial microenvironment, which plays an important role in cardiomyocyte proliferation and heart regeneration.

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“…Currently, there are no effective clinical treatments to limit I/RI . Principal progresses have been made in innovative repair strategies for myocardial I/RI, including stem cell-based regenerative therapy, , cardiac patch implantation, exosome-based approaches, and molecular target study, − as well as antioxidant and anti-inflammatory drugs. , Additionally, more attempts that incorporate biocompatible cardiac devices and gene therapy also show potential in promoting beneficial cellular or tissue responses.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle–Patch System for Localized, Effective, and Sustained miRNA Administration into Infarcted Myocardium to Alleviate Myocardial Ischemia–Reperfusion Injury

Chen,

Zhu

et al. 2024

ACS Nano

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Timely blood reperfusion after myocardial infarction (MI) paradoxically triggers ischemia−reperfusion injury (I/RI), which currently has not been conquered by clinical treatments. Among innovative repair strategies for myocardial I/RI, microRNAs (miRNAs) are expected as genetic tools to rescue damaged myocardium. Our previous study identified that miR-30d can provide protection against myocardial apoptosis and fibrosis to alleviate myocardial injury. Although common methods such as liposomes and viral vectors have been used for miRNA transfection, their therapeutic efficiencies have struggled with inefficient in vivo delivery, susceptible inactivation, and immunogenicity. Here, we establish a nanoparticle−patch system for miR-30d delivery in a murine myocardial I/RI model, which contains ZIF-8 nanoparticles and a conductive microneedle patch. Loaded with miR-30d, ZIF-8 nanoparticles leveraging the proton sponge effect enable miR-30d to escape the endocytic pathway, thus avoiding premature degradation in lysosomes. Meanwhile, the conductive microneedle patch offers a distinct advantage by intramyocardial administration for localized, effective, and sustained miR-30d delivery, and it simultaneously releases Au nanoparticles to reconstruct electrical impulses within the infarcted myocardium. Consequently, the nanoparticle−patch system supports the consistent and robust expression of miR-30d in cardiomyocytes. Results from echocardiography and electrocardiogram (ECG) revealed improved heart functions and standard ECG wave patterns in myocardial I/RI mice after implantation of a nanoparticle−patch system for 3 and 6 weeks. In summary, our work incorporated conductive microneedle patch and miR-30d nanodelivery systems to synergistically transcend the limitations of common RNA transfection methods, thus mitigating myocardial I/RI.

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Beyond cardiomyocytes: Cellular diversity in the heart's response to exercise

Cited by 12 publications

References 157 publications

Electrically stimulated in vitro heart cell mimic of acute exercise reveals novel immediate cellular responses to exercise: Reduced contractility and metabolism, but maintained calcium cycling and increased myofilament calcium sensitivity

Electrically stimulated in vitro heart cell mimic of acute exercise reveals novel immediate cellular responses to exercise: Reduced contractility and metabolism, but maintained calcium cycling and increased myofilament calcium sensitivity

Effects and mechanisms of the myocardial microenvironment on cardiomyocyte proliferation and regeneration

Nanoparticle–Patch System for Localized, Effective, and Sustained miRNA Administration into Infarcted Myocardium to Alleviate Myocardial Ischemia–Reperfusion Injury

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