Dynamic regulation of HIF-1 signaling in the rhesus monkey heart after ischemic injury

Wang, Tao; Xiao, Ying; Zhang, Jingyao; Jing, Fujia; Zeng, Guodan

doi:10.1186/s12872-022-02841-0

Cited by 6 publications

(4 citation statements)

References 58 publications

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“…However, whether recovery in humans who survive a neonatal MI persists into adulthood has not yet been established. Adult rhesus macaque (Macaca mulatta) hearts show functional deterioration and fibrosis following MI 56,57 . In two investigations, cardiac regenerative potential was found in 1-day-old and 2-day-old neonatal piglets (Sus domesticus) following MI 58,59 .…”

Section: [H2] Mammalsmentioning

confidence: 99%

Animal models to study cardiac regeneration

Weinberger

Riley

2023

Nat Rev Cardiol

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Permanent fibrosis and chronic deterioration of heart function in human patientsfollowing myocardial infarction present a major healthcare burden worldwide. In contrast to the restricted potential for cellular and functional regeneration of the adult mammalian heart, a robust capacity for cardiac regeneration is seen during the during the neonatal period in mammals as well as in the adults of many fish and amphibian species. However, we lack a complete understanding as to why cardiac regeneration takes place more efficiently in some species than in others. The capacity of the heart to regenerate following injury is controlled by a complex network of cellular and molecular mechanisms that form a regulatory landscape, either permitting or restricting regeneration. In this Review, we provide an overview of the diverse array of vertebrates that have been studied for their cardiac regenerative potential and discuss differential heart regeneration outcomes in closely related species. Additionally, we summarize current knowledge about the core mechanisms that regulate cardiac regeneration across vertebrate species. [H1] IntroductionCardiovascular disease continues to be one of the major causes of death worldwide 1 .Although the survival rate for myocardial infarction (MI) -the death of heart muscle tissue due to a lack of oxygen caused by the disruption of coronary blood flow 2 -has been steadily

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Section: [H2] Mammalsmentioning

confidence: 99%

Animal models to study cardiac regeneration

Weinberger

Riley

2023

Nat Rev Cardiol

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“…Additionally, pathways associated with cancer, which share common systemic pathology and mechanisms with heart failure [ 33 ], were also up-regulated in IR-injured HOs. Furthermore, pathways related to extracellular matrix (ECM)-receptor interaction, PI3K-Akt signaling, and HIF-1 signaling were up-regulated in IR-injured HOs compared to control HOs which are known to play crucial roles in cardiac remodeling [ 34 ], alleviating negative post-infarct changes in myocardium [ 35 ], and modulating post-infarct healing after myocardial ischemic injury [ 36 ], respectively. Interestingly, pathways associated with human papillomavirus, insulin resistance, efferocytosis, longevity genes, and focal adhesion kinase (FAK) inhibition were also found to be up-regulated in IR-injured HOs.…”

Section: Resultsmentioning

confidence: 99%

Modeling acute myocardial infarction and cardiac fibrosis using human induced pluripotent stem cell-derived multi-cellular heart organoids

Song,

Choi,

et al. 2024

Cell Death Dis

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Heart disease involves irreversible myocardial injury that leads to high morbidity and mortality rates. Numerous cell-based cardiac in vitro models have been proposed as complementary approaches to non-clinical animal research. However, most of these approaches struggle to accurately replicate adult human heart conditions, such as myocardial infarction and ventricular remodeling pathology. The intricate interplay between various cell types within the adult heart, including cardiomyocytes, fibroblasts, and endothelial cells, contributes to the complexity of most heart diseases. Consequently, the mechanisms behind heart disease induction cannot be attributed to a single-cell type. Thus, the use of multi-cellular models becomes essential for creating clinically relevant in vitro cell models. This study focuses on generating self-organizing heart organoids (HOs) using human-induced pluripotent stem cells (hiPSCs). These organoids consist of cardiomyocytes, fibroblasts, and endothelial cells, mimicking the cellular composition of the human heart. The multi-cellular composition of HOs was confirmed through various techniques, including immunohistochemistry, flow cytometry, q-PCR, and single-cell RNA sequencing. Subsequently, HOs were subjected to hypoxia-induced ischemia and ischemia-reperfusion (IR) injuries within controlled culture conditions. The resulting phenotypes resembled those of acute myocardial infarction (AMI), characterized by cardiac cell death, biomarker secretion, functional deficits, alterations in calcium ion handling, and changes in beating properties. Additionally, the HOs subjected to IR efficiently exhibited cardiac fibrosis, displaying collagen deposition, disrupted calcium ion handling, and electrophysiological anomalies that emulate heart disease. These findings hold significant implications for the advancement of in vivo-like 3D heart and disease modeling. These disease models present a promising alternative to animal experimentation for studying cardiac diseases, and they also serve as a platform for drug screening to identify potential therapeutic targets.

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“…Even if oxygen is not deficient, it is too late to meet the demand because the reaction process of aerobic oxidation of glucose is too long. However, ATP could be quickly obtained through glycolysis to supply energy to the myocardium [ 19 , 20 ].…”

Section: Resultsmentioning

confidence: 99%

Role of Cx43 in iPSC-CM Damage Induced by Microwave Radiation

Yin,

Xu,

et al. 2023

IJMS

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The heart is one of the major organs affected by microwave radiation, and these effects have been extensively studied. Previous studies have shown that microwave-radiation-induced heart injury might be related to the abnormal expression and distribution of Cx43. In order to make the research model closer to humans, we used iPSC-CMs as the cell injury model to investigate the biological effect and mechanism of iPSC-CM injury after microwave radiation. To model the damage, iPSC-CMs were separated into four groups and exposed to single or composite S-band (2.856 GHz) and X-band (9.375 GHz) microwave radiation sources with an average power density of 30 mW/cm2. After that, FCM was used to detect cell activity, and ELISA was used to detect the contents of myocardial enzymes and injury markers in the culture medium, and it was discovered that cell activity decreased and the contents increased after radiation. TEM and SEM showed that the ultrastructure of the cell membrane, mitochondria, and ID was damaged. Mitochondrial function was aberrant, and glycolytic capacity decreased after exposure. The electrical conduction function of iPSC-CM was abnormal; the conduction velocity was decreased, and the pulsation amplitude was reduced. Wb, qRT-PCR, and IF detections showed that the expression of Cx43 was decreased and the distribution of Cx43 at the gap junction was disordered. Single or composite exposure to S- and X-band microwave radiation caused damage to the structure and function of iPSC-CMs, primarily affecting the cell membrane, mitochondria, and ID. The composite exposure group was more severely harmed than the single exposure group. These abnormalities in structure and function were related to the decreased expression and disordered distribution of Cx43.

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Dynamic regulation of HIF-1 signaling in the rhesus monkey heart after ischemic injury

Cited by 6 publications

References 58 publications

Animal models to study cardiac regeneration

Animal models to study cardiac regeneration

Modeling acute myocardial infarction and cardiac fibrosis using human induced pluripotent stem cell-derived multi-cellular heart organoids

Role of Cx43 in iPSC-CM Damage Induced by Microwave Radiation

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