Intercellular Communication in the Heart: Therapeutic Opportunities for Cardiac Ischemia

Intercellular communication in the heart can either occur directly, via gap junction channels or tunneling nanotubes, or at longer distances involving soluble factors or extracellular vesicles. Besides contributing to the maintenance of myocardial integrity and function, intercellular communication networks established between the different cardiac cell populations are vital to regulate cardiac repair after injury. Therapeutic targeting of cardiac intercellular communication is vital to improve cell engraftment and functional synchronization in cell-based therapies for myocardial infarction. Small peptides targeting Cx43-based channels, gene therapy tools, exogenous extracellular vesicle administration, and remote conditioning constitute promising strategies to reduce infarct size and enhance repair after acute myocardial infarction. The maintenance of tissue, organ, and organism homeostasis relies on an intricate network of players and mechanisms that assist in the different forms of cell–cell communication. Myocardial infarction, following heart ischemia and reperfusion, is associated with profound changes in key processes of intercellular communication, involving gap junctions, extracellular vesicles, and tunneling nanotubes, some of which have been implicated in communication defects associated with cardiac injury, namely arrhythmogenesis and progression into heart failure. Therefore, intercellular communication players have emerged as attractive powerful therapeutic targets aimed at preserving a fine-tuned crosstalk between the different cardiac cells in order to prevent or repair some of harmful consequences of heart ischemia and reperfusion, re-establishing myocardial function. The maintenance of tissue, organ, and organism homeostasis relies on an intricate network of players and mechanisms that assist in the different forms of cell–cell communication. Myocardial infarction, following heart ischemia and reperfusion, is associated with profound changes in key processes of intercellular communication, involving gap junctions, extracellular vesicles, and tunneling nanotubes, some of which have been implicated in communication defects associated with cardiac injury, namely arrhythmogenesis and progression into heart failure. Therefore, intercellular communication players have emerged as attractive powerful therapeutic targets aimed at preserving a fine-tuned crosstalk between the different cardiac cells in order to prevent or repair some of harmful consequences of heart ischemia and reperfusion, re-establishing myocardial function. term used to describe the spectrum of clinical manifestations associated with a sudden reduction in coronary blood flow, including ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina. atherosclerotic plaque disruption with subsequent thrombus formation, which constitutes the major cause of acute coronary syndrome. passive spread of charge between electrical-excitable cells (e.g., via GJ). Electrotonic potentials can lead to membrane depolarization above the threshold, triggering action potentials. process whereby cells internalize proteins, microorganisms, or other macromolecules from the external environment, involving membrane invagination. involves the generation of electrical fields through the extracellular space, altering the excitability of neighboring cells. microscopy-based method to determine the diffusion kinetics of a fluorescent molecule. After bleaching a defined region of interest, using high laser power, the movement of nonbleached fluorescent molecules into the photobleached area is monitored by time-lapse imaging. interactions established by cells of the same type. specialized region at the cell ends of cardiomyocytes that ensures mechanical and electrical coupling. IDs are composed of three main structures: desmosomes, adherens junctions, and GJs. accumulation of excess fluid in the extracellular space due to water leakage from damaged capillaries. characterized by several brief episodes of ischemia (or hypoxia) prior to a longer period of detrimental ischemia. type of non-coding RNA with over 200 nucleotides, associated with regulation of chromatin structure, alternative splicing, and protein complex scaffolding. formation of new lymphatic vessels, usually from pre-existing vessels, which can occur during heart development or in response to injury. plasma membrane juxtapositions that serve as a conduit for GJ-mediated transfer of molecules between endothelial and vascular smooth muscle cells. technique that involves the use of light to control genetically modified cells or organisms, engineered to express light-sensitive ion channels. self-organized 3D multicellular in vitro tissue construct, derived from stem cells, which can recapitulate organ architecture with high fidelity. membrane microdomain at the periphery of the GJ plaque that plays important roles in GJ formation and facilitates ephaptic coupling. generally, refers to the enzymatic modification of proteins, which can occur as part of their biosynthetic pathway (after protein translation) or during the normal protein lifecycle. Phosphorylation and ubiquitination are two of the most common types. technique that relies on the loading of a membrane-impermeable and GJ-permeable fluorescent dye (e.g., Lucifer yellow) by scraping a cell monolayer. Dye diffusion into neighboring cells connected by functional GJ can be monitored by microscopy. tangential stress generated by the blood flowing on the endothelial surface of the arterial wall.