Adapting to a new environment: postnatal maturation of the human cardiomyocyte

Salameh, Shatha; Ogueri, Vanessa; Posnack, Nikki Gillum

doi:10.1113/jp283792

Cited by 10 publications

(8 citation statements)

References 228 publications

(418 reference statements)

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“…Finally, we note that others have observed significantly slower and smaller calcium transients in pediatric cardiomyocytes 12,30 . We observed a statistically significant increase in calcium amplitude with older age ( Figure 5 ), which can also be influenced by structural changes to the cardiomyocyte (i.e., sarcoplasmic reticulum calcium content, t-tubule development) 7 that are not included within this computational model.…”

Section: Resultsmentioning

confidence: 99%

“…During postnatal life, the mammalian heart undergoes a series of developmental changes that facilitate the transition from the intrauterine to extrauterine environment. Throughout this developmental process, cardiomyocytes adjust to hemodynamic demands by increasing their size, enhancing structural organization, and adapting their electrophysiological and contractile properties 7 . Studies suggest that human cardiomyocytes evolve within the first year of life – but, may not reach full maturity until nearly a decade after birth.…”

Section: Introductionmentioning

confidence: 99%

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Connecting Transcriptomics with Computational Modeling to Reveal Developmental Adaptations in the Human Pediatric Myocardium

Salameh,

Guerrelli,

Miller

et al. 2024

Preprint

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Background: Nearly 1% or 1.3 million babies are born with CHD globally each year, many of whom will require palliative or corrective heart surgery within the first few years of life. A detailed understanding of cardiac maturation can help to expand our knowledge on cardiac diseases that develop during gestation, identify age-appropriate cardiovascular drug therapies, and inform clinical care decisions related to surgical repair, myocardial preservation, or postoperative management. Yet, to date, our knowledge of the temporal changes that cardiomyocytes undergo during postnatal development is largely limited to animal models. Methods: Right atrial tissue samples were collected from n=117 neonatal, infant, and pediatric patients undergoing correct surgery due to (acyanotic) congenital heart disease (CHD). Patients were stratified into five age groups: neonate (0-30 days), infant (31–364 days), toddler to preschool (1–5 years), school age (6–11 years), and adolescent to young adults (12–32 years). We measured age-dependent adaptations in cardiac gene expression, and used computational modeling to simulate action potential and calcium transients. Results: Enrichment of differentially expressed genes (DEG) was explored, revealing age-dependent changes in several key biological processes (cell cycle, cell division, mitosis), cardiac ion channels, and calcium handling genes. Gene–associated changes in ionic currents exhibited both linear trends and sudden shifts across developmental stages, with changes in calcium handling (INCX) and repolarization (IK1) most strongly associated with an age-dependent decrease in the action potential plateau potential and increase in triangulation, respectively. We also note a shift in repolarization reserve, with lower IKr expression in younger patients, a finding likely tied to the increased amplitude of IKs triggered by elevated sympathetic activation in pediatric patients. Conclusion: This study provides valuable insights into age–dependent changes in human cardiac gene expression and electrophysiology among patients with CHD, shedding light on molecular mechanisms underlying cardiac development and function across different developmental stages.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Connecting Transcriptomics with Computational Modeling to Reveal Developmental Adaptations in the Human Pediatric Myocardium

Salameh,

Guerrelli,

Miller

et al. 2024

Preprint

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“…This higher weighting may also be of use to improve the performance of single ECG afflicted pairs with left bundle branch abnormality, for example. The performance drops seen in the paediatric cases, indicative of rapidly changing cardiac electrophysiology 43 and thus ECG biometric features, suggest the need for future studies to focus on paediatric performance.…”

Section: Discussionmentioning

confidence: 99%

Unlocking the potential of artificial intelligence in electrocardiogram biometrics: age-related changes, anomaly detection, and data authenticity in mobile health platforms

Mangold,

Carter,

Siontis

et al. 2024

European Heart Journal - Digital Health

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Aims Mobile devices such as smartphones and watches can now record single-lead electrocardiograms (ECGs), making wearables a potential screening tool for cardiac and wellness monitoring outside of healthcare settings. Because friends and family often share their smart phones and devices, confirmation that a sample is from a given patient is important before it is added to the electronic health record. Methods and results We sought to determine whether the application of Siamese neural network would permit the diagnostic ECG sample to serve as both a medical test and biometric identifier. When using similarity scores to discriminate whether a pair of ECGs came from the same patient or different patients, inputs of single-lead and 12-lead medians produced an area under the curve of 0.94 and 0.97, respectively. Conclusion The similar performance of the single-lead and 12-lead configurations underscores the potential use of mobile devices to monitor cardiac health.

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“…This discrepancy may be attributed to the species differences and the experimental model used in each study. As examples, rodent ventricular cardiomyocytes have a shorter action potential duration and rely more heavily on the sarcoendoplasmic reticulum calcium ATPase for calcium removal compared to human cells (Bers 2008; Ripplinger et al 2022); yet, hiPSC-CM do not fully replicate adult human ventricular myocytes given their automaticity and immature calcium handling machinery (Karbassi et al 2020; Salameh et al 2023). Nevertheless, comparative studies have demonstrated excellent correlation between FPDc measurements in hiPSC-CM and clinical QTc measurements in response to pharmacological agents – supporting the use of hiPSC-CM as a translational model and screening tool for toxicological assessments (Blinova et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Comparative cardiotoxicity assessment of bisphenol chemicals and estradiol using human induced pluripotent stem cell-derived cardiomyocytes

Cooper,

Salameh,

Posnack

2023

Preprint

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Background: Bisphenol A (BPA) is commonly used to manufacture consumer and medical grade plastics. Due to health concerns, BPA substitutes are being incorporated, including bisphenol S (BPS) and bisphenol F (BPF), without a comprehensive understanding of their toxicological profile. Objective: Previous studies suggest that bisphenol chemicals perturb cardiac electrophysiology in a manner that is similar to beta estradiol (E2). We aimed to compare the effects of E2 with BPA, BPF, and BPS using human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM). Methods: Cardiac parameters were evaluated using microelectrode array (MEA) technology and live cell fluorescent imaging at baseline and in response to chemical exposure (0.001-100 uM). Results: Cardiac metrics remained relatively stable after exposure to nanomolar concentrations (1-1,000 nM) of E2, BPA, BPF, or BPS. At higher micromolar concentrations, chemical exposures resulted in a decrease in the depolarizing spike amplitude, shorter field potential and action potential duration, shorter calcium transient duration, and decrease in hiPSC-CM contractility (E2 > BPA > BPF >> BPS). Cardiomyocyte physiology was largely undisturbed by BPS exposure. BPA induced effects were exaggerated when co-administered with an L-type calcium channel antagonist (verapamil) or E2, and reduced when co-administered with an L type calcium channel agonist (Bay K8644) or an estrogen receptor alpha antagonist (MPP). E2 induced effects generally mirrored those of BPA, but were not exaggerated by coadministration with an L-type calcium channel antagonist. Discussion: Collectively across multiple cardiac endpoints, E2 was the most potent and BPS was the least potent disruptor of hiPSC-CM function. Although the observed cardiac effects of E2 and BPA were similar, a few distinct differences suggest that these chemicals may act (in part) through different mechanisms. hiPSC-CM are a useful model for screening cardiotoxic chemicals, nevertheless, the described in vitro findings should be validated using a more complex ex vivo and/or in vivo model.

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Adapting to a new environment: postnatal maturation of the human cardiomyocyte

Abstract: support-information-section).

Cited by 10 publications

References 228 publications

Connecting Transcriptomics with Computational Modeling to Reveal Developmental Adaptations in the Human Pediatric Myocardium

Connecting Transcriptomics with Computational Modeling to Reveal Developmental Adaptations in the Human Pediatric Myocardium

Unlocking the potential of artificial intelligence in electrocardiogram biometrics: age-related changes, anomaly detection, and data authenticity in mobile health platforms

Comparative cardiotoxicity assessment of bisphenol chemicals and estradiol using human induced pluripotent stem cell-derived cardiomyocytes

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