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Advances in Experimental Medicine and... 2017Myocarditis is the inflammation of the muscle tissues of the heart (myocardium). After a pathologic cardiac-specific inflammatory process, it may progress to chronic... (Review)
Review
Myocarditis is the inflammation of the muscle tissues of the heart (myocardium). After a pathologic cardiac-specific inflammatory process, it may progress to chronic damage and dilated cardiomyopathy. The latter is characterized by systolic dysfunction, whose clinical correlate is heart failure. Nevertheless, other acute complications may arise as consequence of tissue damage and electrophysiologic disturbances. Different etiologies are involved in triggering myocarditis. In some cases, such as giant cell myocarditis or eosinophilic necrotizing myocarditis, it is an autoimmune process. Several factors predispose the development of autoimmune myocarditis such as systemic/local primary autoimmunity, viral infection, HLA and gender bias, exposure of cryptic antigens, mimicry, and deficient thymic training/Treg induction. Once the anti-myocardium autoimmune process is triggered, several components of the immune response orchestrate a sustained attack toward myocardial tissues with particular timing and immunopathogenic features. Innate response mediated by monocytes/macrophages, neutrophils, and eosinophils parallels the adaptive response, playing a final effector role and not only a priming function. Stromal cells like fibroblast are also involved in the process through specific cytokines. Furthermore, adaptive T cell responses have anti-paradigmatic features, as Th17 response is dispensable for acute myocarditis but is the main driver of the process leading to dilated cardiomyopathy. Humoral response, thought to be a bystander, is important in the appearance of late-stage hemodynamic complications. The complexity of that process, as well as the unspecific and variable clinical presentation, had generated difficulties for diagnosis and treatment, which remain suboptimal. In this chapter, we will discuss the most relevant immunopathogenic findings from a basic science and clinical perspective.
Topics: Animals; Autoimmune Diseases; Autoimmunity; Disease Models, Animal; Humans; Immunosuppressive Agents; Myocarditis; Myocardium; Prognosis; Risk Factors; Signal Transduction
PubMed: 28667560
DOI: 10.1007/978-3-319-57613-8_10 -
Heart Failure Clinics Jan 2021Advances in technology have made it possible to image the microstructure of the heart with diffusion-weighted magnetic resonance. The technique provides unique insights... (Review)
Review
Advances in technology have made it possible to image the microstructure of the heart with diffusion-weighted magnetic resonance. The technique provides unique insights into the cellular architecture of the myocardium and how this is perturbed in a range of disease contexts. In this review, the physical basis of diffusion MRI and the challenges of implementing it in the beating heart are discussed. Cutting edge acquisition and analysis techniques, as well as the results of initial clinical studies, are reported.
Topics: Humans; Magnetic Resonance Imaging, Cine; Magnetic Resonance Spectroscopy; Myocardium
PubMed: 33220889
DOI: 10.1016/j.hfc.2020.08.007 -
Medecine Sciences : M/S 2017The lymphatic system is a network of vessels and lymphoid tissues that maintain tissue fluid homeostasis, transport intestinal fat, and regulate immune surveillance.... (Review)
Review
The lymphatic system is a network of vessels and lymphoid tissues that maintain tissue fluid homeostasis, transport intestinal fat, and regulate immune surveillance. Despite a large body of evidence showing the importance of lymphatic vessels in cardiovascular diseases, the role of cardiac lymphatics has not been extensively investigated. This review highlights the chronology of key discoveries in cardiac lymphatic development and function. In physiology, the cardiac lymphatic system dynamically regulates interstitial fluid drainage to the mediastinal lymph nodes to maintain homeostasis and prevent edema. After myocardial infarction, lymphatic vessels in the ischemic heart become dysfunctional and contribute to the development of chronic myocardial edema that aggravates cardiac fibrosis and dysfunction. Stimulation of cardiac lymphangiogenesis, based on the delivery of lymphangiogenic growth factors, such as VEGF-C, may represent a novel therapeutic strategy to improve cardiac function.
Topics: Animals; Extracellular Fluid; Heart; Homeostasis; Humans; Lymphangiogenesis; Lymphatic Vessels; Myocardium
PubMed: 28945567
DOI: 10.1051/medsci/20173308022 -
Cellular Signalling Jan 2021The heart can respond to increased pathophysiological demand through alterations in tissue structure and function . This process, called cardiac remodeling, is... (Review)
Review
The heart can respond to increased pathophysiological demand through alterations in tissue structure and function . This process, called cardiac remodeling, is particularly evident following myocardial infarction (MI), where the blockage of a coronary artery leads to widespread death of cardiac muscle. Following MI, necrotic tissue is replaced with extracellular matrix (ECM), and the remaining viable cardiomyocytes (CMs) undergo hypertrophic growth. ECM deposition and cardiac hypertrophy are thought to represent an adaptive response to increase structural integrity and prevent cardiac rupture. However, sustained ECM deposition leads to the formation of a fibrotic scar that impedes cardiac compliance and can induce lethal arrhythmias. Resident cardiac fibroblasts (CFs) are considered the primary source of ECM molecules such as collagens and fibronectin, particularly after becoming activated by pathologic signals. CFs contribute to multiple phases of post-MI heart repair and remodeling, including the initial response to CM death, immune cell (IC) recruitment, and fibrotic scar formation. The goal of this review is to describe how resident fibroblasts contribute to the healing and remodeling that occurs after MI, with an emphasis on how fibroblasts communicate with other cell types in the healing infarct scar .
Topics: Animals; Extracellular Matrix; Fibroblasts; Humans; Matrix Metalloproteinases; Myocardial Infarction; Myocardium; Proteoglycans; Transforming Growth Factor beta1; Ventricular Remodeling
PubMed: 33144186
DOI: 10.1016/j.cellsig.2020.109824 -
Open Biology Aug 2020Diversity among highly specialized cells underlies the fundamental biology of complex multi-cellular organisms. One of the essential scientific questions in cardiac... (Review)
Review
Diversity among highly specialized cells underlies the fundamental biology of complex multi-cellular organisms. One of the essential scientific questions in cardiac biology has been to define subpopulations within the heart. The heart parenchyma comprises specialized cardiomyocytes (CMs). CMs have been canonically classified into a few phenotypically diverse subpopulations largely based on their function and anatomic localization. However, there is growing evidence that CM subpopulations are in fact numerous, with a diversity of genetic origin and putatively different roles in physiology and pathophysiology. In this chapter, we introduce a recently discovered CM subpopulation: phenylethanolamine--methyl transferase (Pnmt)-derived cardiomyocytes (PdCMs). We discuss: (i) canonical classifications of CM subpopulations; (ii) discovery of PdCMs; (iii) Pnmt and the role of catecholamines in the heart; similarities and dissimilarities of PdCMs and canonical CMs; and (iv) putative functions of PdCMs in both physiological and pathological states and future directions, such as in intra-cardiac adrenergic signalling.
Topics: Age Factors; Animals; Biomarkers; Catecholamines; Cell Plasticity; Electrophysiological Phenomena; Humans; Myocardium; Myocytes, Cardiac; Organogenesis; Phenotype; Phenylethanolamine N-Methyltransferase
PubMed: 32810421
DOI: 10.1098/rsob.200095 -
Medecine Sciences : M/S May 2022For the last 20 years, integrins have been a therapeutic target of interest in the treatment of fibrotic diseases, particularly regarding the integrins of the αV... (Review)
Review
For the last 20 years, integrins have been a therapeutic target of interest in the treatment of fibrotic diseases, particularly regarding the integrins of the αV family. Initially developed as anti-cancer drugs but with modest benefits, inhibitors of integrins (such as the anti-αV cilengitide) have shown interesting anti-fibrotic effects in different organs including the heart. Cardiac fibrosis is defined as an accumulation of stiff extracellular matrix in the myocardium, and ultimately leads to heart failure, one of the leading causes of mortality worldwide. Understanding the determinants of cardiac fibrosis and the involvement of integrins is a major matter of public health. This review presents the current knowledge on the different types of cardiac fibrosis and their etiologies, and report on first data supporting specific integrin inhibition therapy as a novel anti-fibrotic strategy, in particular to treat cardiac fibrosis.
Topics: Extracellular Matrix; Fibrosis; Humans; Integrins; Myocardium
PubMed: 35608466
DOI: 10.1051/medsci/2022055 -
Nature Metabolism Jan 2023Investigation of multi-omic changes and their effects on regulation of metabolic pathways confirm anaplerotic deficiencies in methylmalonic acidaemia, strengthening the...
Investigation of multi-omic changes and their effects on regulation of metabolic pathways confirm anaplerotic deficiencies in methylmalonic acidaemia, strengthening the need for future therapies aimed at replenishing intermediates of the tricarboxylic acid cycle.
Topics: Myocardium; Citric Acid Cycle
PubMed: 36717753
DOI: 10.1038/s42255-022-00724-4 -
The Journal of Physiology Jun 2017Myocardial remuscularization can be achieved by cardiomyocyte implantation. Electromechanical integration and long-term survival of cardiomyocyte grafts are essential... (Review)
Review
Myocardial remuscularization can be achieved by cardiomyocyte implantation. Electromechanical integration and long-term survival of cardiomyocyte grafts are essential for maximal therapeutic impact. Cardiomyocyte application with support material has been instrumental in enhancing cell retention. Co-administration of pro-survival factors and immunological matching are additional strategies for increased cell graft survival. Finally, larger cardiomyocyte grafts, although therapeutically desirable, will increase the risk for arrhythmias and, if pluripotent stem cells are used to derive cardiomyocytes, tumour formation. This review introduces major challenges pertaining to myocardial remuscularization (cardiomyocyte retention, arrhythmogenicity and tumourigenicity), discusses studies addressing these challenges, and suggests strategies to overcome remaining challenges for the translation of myocardial remuscularization.
Topics: Animals; Arrhythmias, Cardiac; Cell Survival; Heart Failure; Myocardium; Myocytes, Cardiac; Regeneration
PubMed: 28295371
DOI: 10.1113/JP273098 -
Circulation Journal : Official Journal... Oct 2016Cardiac fibrosis remains an important health concern, but the study of fibroblast biology has been hindered by a lack of effective means for identifying and tracking... (Review)
Review
Cardiac fibrosis remains an important health concern, but the study of fibroblast biology has been hindered by a lack of effective means for identifying and tracking fibroblasts. Recent advances in fibroblast-specific lineage tags and reporters have permitted a better understanding of these cells. After injury, multiple cell types have been implicated as the source for extracellular matrix-producing cells, but emerging studies suggest that resident cardiac fibroblasts contribute substantially to the remodeling process. In this review, we discuss recent findings regarding cardiac fibroblast origin and identity. Our understanding of cardiac fibroblast biology and fibrosis is still developing and will expand profoundly in the next few years, with many of the recent findings regarding fibroblast gene expression and behavior laying down the groundwork for interpreting the purpose and utility of these cells before and after injury. (Circ J 2016; 80: 2269-2276).
Topics: Animals; Fibroblasts; Fibrosis; Gene Expression Regulation; Heart Diseases; Humans; Myocardium
PubMed: 27746422
DOI: 10.1253/circj.CJ-16-1003 -
Journal of Molecular and Cellular... Mar 2016Fibrosis is defined as excess deposition of extracellular matrix (ECM), resulting in tissue scarring and organ dysfunction. In the heart, fibrosis may be reparative,... (Review)
Review
Fibrosis is defined as excess deposition of extracellular matrix (ECM), resulting in tissue scarring and organ dysfunction. In the heart, fibrosis may be reparative, replacing areas of myocyte loss with a structural scar following infarction, or reactive, which is triggered in the absence of cell death and involves interstitial ECM deposition in response to long-lasting stress. Interstitial fibrosis can increase the passive stiffness of the myocardium, resulting in impaired relaxation and diastolic dysfunction. Additionally, fibrosis can lead to disruption of electrical conduction in the heart, causing arrhythmias, and can limit myocyte oxygen availability and thus exacerbate myocardial ischemia. Here, we review recent studies that have illustrated key roles for epigenetic events in the control of pro-fibrotic gene expression, and highlight the potential of small molecules that target epigenetic regulators as a means of treating fibrotic cardiac diseases.
Topics: Epigenesis, Genetic; Extracellular Matrix; Fibrosis; Heart Failure; Humans; Myocardium
PubMed: 26876451
DOI: 10.1016/j.yjmcc.2016.02.011