ArticleAmerican journal of physiology. Heart and circulatory physiology2020
Contractile work directly modulates mitochondrial protein levels in human engineered heart tissues.
Article in American journal of physiology. Heart and circulatory physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 17 citations in OpenAlex.
- Review
- Hearts may grow concentrically to balance ATP supply and demand and eccentrically to stabilize titin-based stress.bioRxiv : the preprint server for biology · 2026Article
- Human-Induced Pluripotent Stem Cell Models for Amyloid Cardiomyopathy: From Mechanistic Insights to Therapeutic Discovery.Journal of cardiovascular development and disease · 2025Review
- Advancements in techniques for human iPSC-derived cardiomyocytes maturation: mechanical and electrical stimulation approaches.Biophysical reviews · 2025Review
- Induced pluripotent stem cell-derived cardiomyocyte in vitro models: benchmarking progress and ongoing challenges.Nature methods · 2025Review
- Engineered heart tissue: Design considerations and the state of the art.Biophysics reviews · 2024Review
- Chronic diastolic stretch unmasks conduction defects in an in vitro model of arrhythmogenic cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2023Article
- Rational engineering of lung alveolar epithelium.NPJ Regenerative medicine · 2023Article
- Increased length-dependent activation of human engineered heart tissue after chronic αAmerican journal of physiology. Heart and circulatory physiology · 2023Article
- Modelling Diabetic Cardiomyopathy: Using Human Stem Cell-Derived Cardiomyocytes to Complement Animal Models.Metabolites · 2022Review
- Remodelling of adult cardiac tissue subjected to physiological and pathological mechanical load in vitro.Cardiovascular research · 2022Article
- Human Engineered Heart Tissue Models for Disease Modeling and Drug Discovery.Frontiers in cell and developmental biology · 2022Review
- Evidence for synergy between sarcomeres and fibroblasts in an in vitro model of myocardial reverse remodeling.Journal of molecular and cellular cardiology · 2021Article
- Cardiac mechanostructure: Using mechanics and anisotropy as inspiration for developing epicardial therapies in treating myocardial infarction.Bioactive materials · 2021Review
- Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes.Stem cell research & therapy · 2021Review
- Shortening Velocity Causes Myosin Isoform Shift in Human Engineered Heart Tissues.Circulation research · 2021Article
- An American Physiological Society cross-journal Call for Papers on "Deconstructing Organs: Single-Cell Analyses, Decellularized Organs, Organoids, and Organ-on-a-Chip Models".American journal of physiology. Lung cellular and molecular physiology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Engineered heart tissues (EHTs) have emerged as a robust in vitro model to study cardiac physiology. Although biomimetic culture environments have been developed to better approximate in vivo conditions, currently available methods do not permit full recapitulation of the four phases of the cardiac cycle. We have developed a bioreactor which allows EHTs to undergo cyclic loading sequences that mimic in vivo work loops. EHTs cultured under these working conditions exhibited enhanced concentric contractions but similar isometric contractions compared with EHTs cultured isometrically. EHTs that were allowed to shorten cyclically in culture had increased capacity for contractile work when tested acutely. Increased work production was correlated with higher levels of mitochondrial proteins and mitochondrial biogenesis; this effect was eliminated when tissues were cyclically shortened in the presence of a myosin ATPase inhibitor. Leveraging our novel in vitro method to precisely apply mechanical loads in culture, we grew EHTs under two loading regimes prescribing the same work output but with different associated afterloads. These groups showed no difference in mitochondrial protein expression. In loading regimes with the same afterload but different work output, tissues subjected to higher work demand exhibited elevated levels of mitochondrial protein. Our findings suggest that regulation of mitochondrial mass in cultured human EHTs is potently modulated by the mechanical work the tissue is permitted to perform in culture, presumably communicated through ATP demand. Precise application of mechanical loads to engineered heart tissues in culture represents a novel in vitro method for studying physiological and pathological cardiac adaptation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.