Human heart
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Understanding the Human Heart: Cellular Composition, Development, and Function
Cellular Heterogeneity in the Human Heart
The human heart is composed of a diverse array of cell types, each playing a crucial role in its function. Recent studies using advanced single-cell and single-nucleus RNA sequencing have mapped the cellular landscape of the adult human heart, revealing significant heterogeneity among cardiomyocytes, pericytes, and fibroblasts. These studies have identified distinct subsets of atrial and ventricular cells, each with unique developmental origins and specialized properties . Additionally, the cardiac vasculature exhibits complexity and variation along the arterio-venous axis, and the immune compartment includes cardiac-resident macrophages with both inflammatory and protective roles.
Developmental Trajectory of Cardiac Cells
The development of the human heart involves the differentiation of several major cell types, including cardiomyocytes (CMs), cardiac fibroblasts, endothelial cells (ECs), and valvar interstitial cells (VICs). Single-cell RNA sequencing of human embryonic hearts has shown that atrial and ventricular CMs acquire distinct features early in development. Both CMs and fibroblasts undergo stepwise changes in gene expression as development progresses, with VICs playing a role in the remodeling phase and ECs displaying location-specific characteristics. Comparative studies between human and mouse hearts have highlighted unique aspects of human cardiac development, providing insights into potential mechanisms of cardiac regeneration.
Postconditioning and Myocardial Protection
Postconditioning, a technique involving brief periods of ischemia at the time of reperfusion, has been shown to reduce infarct size in animal models. A clinical study investigating the effects of postconditioning during coronary angioplasty for acute myocardial infarction found that this technique significantly reduced infarct size and improved myocardial reperfusion without adverse events. This suggests that postconditioning can protect the human heart during acute myocardial infarction.
Excitation and Conduction in the Human Heart
Studies on isolated human hearts have provided detailed information on the time course and distribution of the excitatory process. Measurements from intramural terminals have shown that specific endocardial areas are synchronously excited shortly after the onset of left ventricular activity. The excitation pattern spreads rapidly, with the left ventricular areas becoming confluent within 15 to 20 milliseconds. The right ventricle and septum also exhibit distinct activation patterns, reflecting the movements of the intramural excitation wave.
Electro-Fluid-Mechanics and Computational Models
The dynamics of the human heart involve complex interactions between fluid mechanics, electrophysiology, and elastomechanics. Advanced computational models have been developed to simulate the integrative electro-mechanical response of the heart, providing valuable insights into its function. These models, which include high-fidelity simulations and reduced models to manage computational costs, are essential for understanding the heart's behavior and guiding clinical interventions .
Translational Regulation and Microproteins
Gene expression in the human heart is subject to extensive translational control, which orchestrates cardiac gene expression in a process-specific manner. Studies have identified hundreds of previously undetected microproteins expressed from lncRNAs and circRNAs, many of which are associated with diverse cellular processes and compartments, including the mitochondria. These findings highlight the complexity of translational regulation and its implications for cardiac function.
Metabolic Function and Fuel Use
The heart's metabolic function is critical for its continuous contraction. Metabolomic studies have quantified the uptake and release of various metabolites by the human heart, revealing a preference for fatty acids as the primary fuel source. The heart also secretes amino acids, indicating active proteolysis, and consumes ketones and lactate, especially in heart failure conditions. These insights into cardiac metabolism could inform strategies for combating heart disease.
Conclusion
The human heart is a complex organ with diverse cellular composition, intricate developmental processes, and sophisticated functional dynamics. Advances in single-cell sequencing, clinical studies, and computational modeling have significantly enhanced our understanding of cardiac physiology and pathology. These insights pave the way for developing new therapeutic strategies and improving clinical outcomes for cardiovascular diseases.
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