Properties and Immune Function of Cardiac Fibroblasts

Furtado, Milena B.; Hasham, Muneer G.

doi:10.1007/978-3-319-57613-8_3

Cited by 12 publications

(7 citation statements)

References 187 publications

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“…On the other hand, by their biophysical interactions with cardiomyocytes through mechanical or electrical junctions, fibroblasts can facilitate electro-mechanical transduction important for the proper maintenance of the conduction system (74, 75). Upon insult, fibroblasts initiate production of ECM components for tissue reconstruction (76) and transmit signals to surrounding cardiomyocytes, but also to other stromal cells for initiation of the healing process (23, 77–79). However, alterations of fibroblast behavior in response to extrinsic factors, such as inflammatory cytokines, and persistent activation lead to deregulated matrix deposition and consequently to the formation of fibrotic tissue, underlining the pivotal role of fibroblasts in regulating the equilibrium between disease development and tissue repair and regeneration in the heart (70, 80–82) and other tissues (83–85).…”

Section: Cardiac Subpopulations and The Contribution Of Innate Immunitymentioning

confidence: 99%

Three in a Box: Understanding Cardiomyocyte, Fibroblast, and Innate Immune Cell Interactions to Orchestrate Cardiac Repair Processes

Psarras

Beis

Nikouli

et al. 2019

Front. Cardiovasc. Med.

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Following an insult by both intrinsic and extrinsic pathways, complex cellular, and molecular interactions determine a successful recovery or inadequate repair of damaged tissue. The efficiency of this process is particularly important in the heart, an organ characterized by very limited regenerative and repair capacity in higher adult vertebrates. Cardiac insult is characteristically associated with fibrosis and heart failure, as a result of cardiomyocyte death, myocardial degeneration, and adverse remodeling. Recent evidence implies that resident non-cardiomyocytes, fibroblasts but also macrophages -pillars of the innate immunity- form part of the inflammatory response and decisively affect the repair process following a cardiac insult. Multiple studies in model organisms (mouse, zebrafish) of various developmental stages (adult and neonatal) combined with genetically engineered cell plasticity and differentiation intervention protocols -mainly targeting cardiac fibroblasts or progenitor cells-reveal particular roles of resident and recruited innate immune cells and their secretome in the coordination of cardiac repair. The interplay of innate immune cells with cardiac fibroblasts and cardiomyocytes is emerging as a crucial platform to help our understanding and, importantly, to allow the development of effective interventions sufficient to minimize cardiac damage and dysfunction after injury.

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Section: Cardiac Subpopulations and The Contribution Of Innate Immunitymentioning

confidence: 99%

Three in a Box: Understanding Cardiomyocyte, Fibroblast, and Innate Immune Cell Interactions to Orchestrate Cardiac Repair Processes

Psarras

Beis

Nikouli

et al. 2019

Front. Cardiovasc. Med.

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show abstract

“…Studies in murine models have identified that cardiac fibroblasts make up close to 25% of the heart tissue ( 17 ). While not possessing electrical or contractile functions themselves, cardiac fibroblasts can couple to cardiomyocytes to aid in the propagation of electrical signals, maintain extracellular matrix homeostasis, and secrete cytokines and chemokines to modulate the immune system ( 18 , 19 ). After injury, these fibroblasts exhibit functions to remodel the ECM, alter chemical and mechanical signals, participate in angiogenesis, and contribute to fibrosis ( 20 , 21 ).…”

Section: Fibroblast To Myofibroblast To Osteoblast-like Cellmentioning

confidence: 99%

Cell Phenotype Transitions in Cardiovascular Calcification

Hortells

Sur

Hilaire

2018

Front. Cardiovasc. Med.

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Cardiovascular calcification was originally considered a passive, degenerative process, however with the advance of cellular and molecular biology techniques it is now appreciated that ectopic calcification is an active biological process. Vascular calcification is the most common form of ectopic calcification, and aging as well as specific disease states such as atherosclerosis, diabetes, and genetic mutations, exhibit this pathology. In the vessels and valves, endothelial cells, smooth muscle cells, and fibroblast-like cells contribute to the formation of extracellular calcified nodules. Research suggests that these vascular cells undergo a phenotypic switch whereby they acquire osteoblast-like characteristics, however the mechanisms driving the early aspects of these cell transitions are not fully understood. Osteoblasts are true bone-forming cells and differentiate from their pluripotent precursor, the mesenchymal stem cell (MSC); vascular cells that acquire the ability to calcify share aspects of the transcriptional programs exhibited by MSCs differentiating into osteoblasts. What is unknown is whether a fully-differentiated vascular cell directly acquires the ability to calcify by the upregulation of osteogenic genes or, whether these vascular cells first de-differentiate into an MSC-like state before obtaining a “second hit” that induces them to re-differentiate down an osteogenic lineage. Addressing these questions will enable progress in preventative and regenerative medicine strategies to combat vascular calcification pathologies. In this review, we will summarize what is known about the phenotypic switching of vascular endothelial, smooth muscle, and valvular cells.

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“…DAMPS alert the immune system of the tissue damage through activation of pattern-recognition receptors (PRRs) present in immune cells as well as in structural cells such as cardiomyocytes, fibroblasts, and endothelial cells 16,3,4 . PRR activation on fibroblasts induces their proliferation, migration, differentiation into myofibroblasts [G] , ECM turnover, and production of fibrotic and inflammatory factors 18,[19][20][21][22][23] . Crucial PRRs involved in the response to myocardial ischaemia are Toll-like receptor (TLR) 2 and TLR4 and the receptor for advanced glycosylation end products (RAGE) 24 .…”

mentioning

confidence: 99%

“…In the injury context, cardiac fibroblasts respond to immunological stimuli and signal to cardiomyocytes 8 , a crucial role in the orchestration of the healing process. Fibroblasts themselves have broad immune-regulatory properties, interpreting inflammatory factors to signal surrounding stromal cells and initiate production of ECM components for tissue reconstruction20 .…”

mentioning

confidence: 99%

The interstitium in cardiac repair: role of the immune–stromal cell interplay

2018

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Cardiac regeneration, that is, restoration of the original structure and function in a damaged heart, differs from tissue repair, in which collagen deposition and scar formation often lead to functional impairment. In both scenarios, the early-onset inflammatory response is essential to clear damaged cardiac cells and initiate organ repair, but the quality and extent of the immune response vary. Immune cells embedded in the damaged heart tissue sense and modulate inflammation through a dynamic interplay with stromal cells in the cardiac interstitium, which either leads to recapitulation of cardiac morphology by rebuilding functional scaffolds to support muscle regrowth in regenerative organisms or fails to resolve the inflammatory response and produces fibrotic scar tissue in adult mammals. Current investigation into the mechanistic basis of homeostasis and restoration of cardiac function has increasingly shifted focus away from stem cell-mediated cardiac repair towards a dynamic interplay of cells composing the less-studied interstitial compartment of the heart, offering unexpected insights into the immunoregulatory functions of cardiac interstitial components and the complex network of cell interactions that must be considered for clinical intervention in heart diseases.

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Properties and Immune Function of Cardiac Fibroblasts

Cited by 12 publications

References 187 publications

Three in a Box: Understanding Cardiomyocyte, Fibroblast, and Innate Immune Cell Interactions to Orchestrate Cardiac Repair Processes

Three in a Box: Understanding Cardiomyocyte, Fibroblast, and Innate Immune Cell Interactions to Orchestrate Cardiac Repair Processes

Cell Phenotype Transitions in Cardiovascular Calcification

The interstitium in cardiac repair: role of the immune–stromal cell interplay

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