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Stem Cell Research Nov 2014Adult mammals undergo minimal regeneration following cardiac injury, which severely compromises cardiac function and contributes to the ongoing burden of heart failure.... (Review)
Review
Adult mammals undergo minimal regeneration following cardiac injury, which severely compromises cardiac function and contributes to the ongoing burden of heart failure. In contrast, the mammalian heart retains a transient capacity for cardiac regeneration during fetal and early neonatal life. Recent studies have established the importance of several evolutionarily conserved mechanisms for heart regeneration in lower vertebrates and neonatal mammals including induction of cardiomyocyte proliferation, epicardial cell activation, angiogenesis, extracellular matrix deposition and immune cell infiltration. In this review, we provide an up-to-date account of the molecular and cellular basis for cardiac regeneration in lower vertebrates and neonatal mammals. The historical context for these recent findings and their ramifications for the future development of cardiac regenerative therapies are also discussed.
Topics: Animals; Animals, Newborn; Cell Proliferation; Heart; Humans; Mice; Myocardium; Regeneration
PubMed: 25108892
DOI: 10.1016/j.scr.2014.06.003 -
Physiological Research Dec 2018More than four decades passed since sigma receptors were first mentioned. Since then, existence of at least two receptor subtypes and their tissue distributions have... (Review)
Review
More than four decades passed since sigma receptors were first mentioned. Since then, existence of at least two receptor subtypes and their tissue distributions have been proposed. Nowadays, it is clear, that sigma receptors are unique ubiquitous proteins with pluripotent function, which can interact with so many different classes of proteins. As the endoplasmic resident proteins, they work as molecular chaperones - accompany various proteins during their folding, ensure trafficking of the maturated proteins between cellular organelles and regulate their functions. In the heart, sigma receptor type 1 is more dominant. Cardiac sigma 1 receptors regulate response to endoplasmic reticulum stress, modulates calcium signaling in cardiomyocyte and can affect function of voltage-gated ion channels. They contributed in pathophysiology of cardiac hypertrophy, heart failure and many other cardiovascular disorders. Therefore, sigma receptors are potential novel targets for specific treatment of cardiovascular diseases.
Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Humans; Myocardium; Myocytes, Cardiac; Receptors, sigma; Sigma-1 Receptor
PubMed: 30607964
DOI: 10.33549/physiolres.934052 -
The Journal of Clinical Investigation Feb 2017Heart failure is a major source of morbidity and mortality. Replacing lost myocardium with new tissue is a major goal of regenerative medicine. Unlike adult mammals,... (Review)
Review
Heart failure is a major source of morbidity and mortality. Replacing lost myocardium with new tissue is a major goal of regenerative medicine. Unlike adult mammals, zebrafish and neonatal mice are capable of heart regeneration following cardiac injury. In both contexts, the regenerative program echoes molecular and cellular events that occur during cardiac development and morphogenesis, notably muscle creation through division of cardiomyocytes. Based on studies over the past decade, it is now accepted that the adult mammalian heart undergoes a low grade of cardiomyocyte turnover. Recent data suggest that this cardiomyocyte turnover can be augmented in the adult mammalian heart by redeployment of developmental factors. These findings and others suggest that stimulating endogenous regenerative responses can emerge as a therapeutic strategy for human cardiovascular disease.
Topics: Animals; Heart Failure; Humans; Mice; Myocardium; Myocytes, Cardiac; Regenerative Medicine; Zebrafish
PubMed: 28145902
DOI: 10.1172/JCI89786 -
Basic Research in Cardiology Dec 2020Resident cardiac macrophages (rcMacs) are integral components of the myocardium where they have key roles for tissue homeostasis and in response to inflammation, tissue... (Review)
Review
Resident cardiac macrophages (rcMacs) are integral components of the myocardium where they have key roles for tissue homeostasis and in response to inflammation, tissue injury and remodelling. In this review, we summarize the current knowledge and limitations associated with the rcMacs studies. We describe their specific role and contribution in various processes such as electrical conduction, efferocytosis, inflammation, tissue development, remodelling and regeneration in both the healthy and the disease state. We also outline research challenges and technical complications associated with rcMac research. Recent technological developments and contemporary immunological techniques are now offering new opportunities to investigate the separate contribution of rcMac in respect to recruited monocytes and other cardiac cells. Finally, we discuss new therapeutic strategies, such as drugs or non-coding RNAs, which can influence rcMac phenotype and their response to inflammation. These novel approaches will allow for a deeper understanding of this cardiac endogenous cell type and might lead to the development of more specific and effective therapeutic strategies to boost the heart's intrinsic reparative capacity.
Topics: Animals; Heart Diseases; Humans; Macrophages; Myocardium; Phagocytosis; Phenotype; Regeneration; Signal Transduction; Ventricular Function, Left; Ventricular Remodeling
PubMed: 33284387
DOI: 10.1007/s00395-020-00836-6 -
Discovery Medicine Mar 2018Stem cells are a promising solution for the treatment of heart failure due to their ability to repopulate injured myocardium and restore cardiac function. However, many... (Review)
Review
Stem cells are a promising solution for the treatment of heart failure due to their ability to repopulate injured myocardium and restore cardiac function. However, many hindrances (such as low survival/viability and integration of transplanted cells, poor homing and cardiac differentiation efficiency, and inadequate cell retention and engraftment) compromise the full regenerative potential provided by stem cells. Therefore, it is necessary to optimize stem cell/progenitor therapy to improve clinical efficacy. By analogy, in order for crops to grow, good seeds are needed. They also need sufficient fertilizer, herbicides, and pesticides to be "optimized." In this review, we provide a comprehensive overview of "seeds" (comparison of stem cell types, different combinations of stem cells, age, size, and dose of stem cells) and "fertilizers" (optimizing stem/progenitor cells and genetic strategies, preconditioning with drugs, and physical changes) for heart failure.
Topics: Animals; Cell Differentiation; Cell Survival; Heart Failure; Humans; Myocardium; Stem Cell Transplantation; Stem Cells
PubMed: 29641973
DOI: No ID Found -
Journal of Investigative Medicine : the... Dec 2009Cardiomyopathy is a heart muscle disease caused by decreased contractility of the ventricles leading to heart failure and premature death. Multiple conditions like... (Review)
Review
Cardiomyopathy is a heart muscle disease caused by decreased contractility of the ventricles leading to heart failure and premature death. Multiple conditions like ischemic heart disease (atherosclerosis), hypertension, diabetes, viral infection, alcohol abuse, obesity and genetic mutations can lead to cardiomyopathy. Single gene mutations in sarcomeric proteins, Z-disk-associated proteins, membrane/associated proteins, intermediate filaments, calcium cycle proteins as well as in modifier genes have been linked to cardiomyopathy. Clinical practice guidelines have been formulated by the American Heart Association and the Heart Failure Association of America on how to genetically evaluate patients with cardiomyopathy. To illustrate the concept that alterations in genes cause cardiovascular disease, this review will focus on two membrane-associated proteins, vinculin and talin. We will discuss the general function of vinculin/metavinulin as well as talin1 and talin2, with emphasis on what is understood about their role in the cardiac myocyte and in whole heart.
Topics: Animals; Cardiomyopathies; Humans; Myocardium; Myocytes, Cardiac; Talin; Vinculin
PubMed: 19952892
DOI: 10.2310/JIM.0b013e3181c5e074 -
Circulation Research Feb 2020The hallmark of most cardiac diseases is the progressive loss of cardiomyocytes. In the perinatal period, cardiomyocytes still proliferate, and the heart shows the... (Review)
Review
The hallmark of most cardiac diseases is the progressive loss of cardiomyocytes. In the perinatal period, cardiomyocytes still proliferate, and the heart shows the capacity to regenerate upon injury. In the adult heart, however, the actual rate of cardiomyocyte renewal is too low to efficiently counteract substantial cell loss caused by cardiac injury. In mammals, cardiac growth by cell number expansion changes to growth by cardiomyocyte enlargement soon after birth, coinciding with a period in which most cardiomyocytes increase their DNA content by multinucleation and nuclear polyploidization. Although cardiomyocyte hypertrophy is often associated with these processes, whether polyploidy is a prerequisite or a consequence of hypertrophic growth is unclear. Both the benefits of cardiomyocyte enlargement over proliferative growth of the heart and the physiological role of polyploidy in cardiomyocytes are enigmatic. Interestingly, hearts in animal species with substantial cardiac regenerative capacity dominantly comprise diploid cardiomyocytes, raising the hypothesis that cardiomyocyte polyploidy poses a barrier for cardiomyocyte proliferation and subsequent heart regeneration. On the contrary, there is also evidence for self-duplication of multinucleated myocytes, suggesting a more complex picture of polyploidy in heart regeneration. Polyploidy is not restricted to the heart but also occurs in other cell types in the body. In this review, we explore the biological relevance of polyploidy in different species and tissues to acquire insight into its specific role in cardiomyocytes. Furthermore, we speculate about the physiological role of polyploidy in cardiomyocytes and how this might relate to renewal and regeneration.
Topics: Animals; Cell Enlargement; Cell Proliferation; DNA; Heart; Humans; Myocardium; Myocytes, Cardiac; Polyploidy; Regeneration; Species Specificity
PubMed: 32078450
DOI: 10.1161/CIRCRESAHA.119.315408 -
Circulation Research Jun 2024Fibroblasts are essential for building and maintaining the structural integrity of all organs. Moreover, fibroblasts can acquire an inflammatory phenotype to accommodate... (Review)
Review
Fibroblasts are essential for building and maintaining the structural integrity of all organs. Moreover, fibroblasts can acquire an inflammatory phenotype to accommodate immune cells in specific niches and to provide migration, differentiation, and growth factors. In the heart, balancing of fibroblast activity is critical for cardiac homeostasis and optimal organ function during inflammation. Fibroblasts sustain cardiac homeostasis by generating local niche environments that support housekeeping functions and by actively engaging in intercellular cross talk. During inflammatory perturbations, cardiac fibroblasts rapidly switch to an inflammatory state and actively communicate with infiltrating immune cells to orchestrate immune cell migration and activity. Here, we summarize the current knowledge on the molecular landscape of cardiac fibroblasts, focusing on their dual role in promoting tissue homeostasis and modulating immune cell-cardiomyocyte interaction. In addition, we discuss potential future avenues for manipulating cardiac fibroblast activity during myocardial inflammation.
Topics: Humans; Homeostasis; Animals; Fibroblasts; Myocardium; Inflammation; Myocarditis; Myocytes, Cardiac; Cell Communication
PubMed: 38843287
DOI: 10.1161/CIRCRESAHA.124.323892 -
Biochimica Et Biophysica Acta.... Aug 2017Although the majority of SUMO substrates are localized in the nucleus, SUMOylation is not limited to nuclear proteins and can be also detected in extra-nuclear proteins.... (Review)
Review
Although the majority of SUMO substrates are localized in the nucleus, SUMOylation is not limited to nuclear proteins and can be also detected in extra-nuclear proteins. In this review, we will highlight and discuss how SUMOylation in different cellular compartments regulate biological processes. First, we will discuss the key role of SUMOylation of proteins in the extra-nuclear compartment in cardiomyocytes, which is overwhelmingly cardio-protective. On the other hand, SUMOylation of nuclear proteins is generally detrimental to the cardiac function mainly because of the trans-repressive nature of SUMOylation on many transcription factors. We will also discuss the potential role of SUMOylation in epigenetic regulation. In this review, we will propose a new concept that shuttling of SUMO proteases between the nuclear and extra-nuclear compartments without changing their enzymatic activity regulates the extent of SUMOylation in these compartments and determines the response and fate of cardiomyocytes after cardiac insults. Approaches focused specifically to inhibit this shuttling in cardiomyocytes will be necessary to understand the whole picture of SUMOylation and its pathophysiological consequences in the heart, especially after cardiac insults. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren & Megan Yingmei Zhang.
Topics: Animals; Heart Diseases; Humans; Muscle Proteins; Myocardium; Myocytes, Cardiac; Sumoylation
PubMed: 28130202
DOI: 10.1016/j.bbadis.2017.01.018 -
GeroScience Feb 2017Age-related changes in cardiac homeostasis can be observed at the cellular, extracellular, and tissue levels. Progressive cardiomyocyte hypertrophy, inflammation, and... (Review)
Review
Age-related changes in cardiac homeostasis can be observed at the cellular, extracellular, and tissue levels. Progressive cardiomyocyte hypertrophy, inflammation, and the gradual development of cardiac fibrosis are hallmarks of cardiac aging. In the absence of a secondary insult such as hypertension, these changes are subtle and result in slight to moderate impaired myocardial function, particularly diastolic function. While collagen deposition and cross-linking increase during aging, extracellular matrix (ECM) degradation capacity also increases due to increased expression of matrix metalloproteinases (MMPs). Of the MMPs elevated with cardiac aging, MMP-9 has been extensively evaluated and its roles are reviewed here. In addition to proteolytic activity on ECM components, MMPs oversee cell signaling during the aging process by modulating cytokine, chemokine, growth factor, hormone, and angiogenic factor expression and activity. In association with elevated MMP-9, macrophage numbers increase in an age-dependent manner to regulate the ECM and angiogenic responses. Understanding the complexity of the molecular interactions between MMPs and the ECM in the context of aging may provide novel diagnostic indicators for the early detection of age-related fibrosis and cardiac dysfunction.
Topics: Aging; Animals; Extracellular Matrix; Heart; Humans; Matrix Metalloproteinases; Myocardium; Myocytes, Cardiac; Prognosis; Time Factors; Ventricular Dysfunction, Left; Ventricular Remodeling
PubMed: 28299638
DOI: 10.1007/s11357-017-9959-9