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BioMed Research International 2018Cardiovascular disease remains the leading cause of morbidity and mortality, imposing a major disease burden worldwide. Therefore, there is an urgent need to identify... (Review)
Review
Cardiovascular disease remains the leading cause of morbidity and mortality, imposing a major disease burden worldwide. Therefore, there is an urgent need to identify new therapeutic targets. Recently, the concept that the heart acts as a secretory organ has attracted increasing attention. Proteins secreted by the heart are called cardiokines, and they play a critical physiological role in maintaining heart homeostasis or responding to myocardial damage and thereby influence the development of heart diseases. Given the critical role of cardiokines in heart disease, they might represent a promising therapeutic target. This review will focus on several cardiokines and discuss their roles in the pathogenesis of heart diseases and as potential therapeutics.
Topics: Heart Diseases; Humans; Molecular Targeted Therapy; Myocardium; Proteins
PubMed: 29744364
DOI: 10.1155/2018/8207058 -
TheScientificWorldJournal Apr 2006The formation of the ventricles of the heart involves numerous carefully regulated temporal events, including the initial specification and deployment of ventricular... (Review)
Review
The formation of the ventricles of the heart involves numerous carefully regulated temporal events, including the initial specification and deployment of ventricular progenitors, subsequent growth and maturation of the ventricles through "ballooning" of chamber myocardium, the emergence of trabeculations, the generation of the compact myocardium, and the formation of the interventricular septum. Several genes have been identified through studies on mouse knockout and transgenic models, which have contributed to our understanding of the molecular events governing these developmental processes. Interpretation of these studies highlights the fact that even the smallest perturbation at any stage of ventricular development may lead to cardiac malformations that result in either early embryonic mortality or a manifestation of congenital heart disease.
Topics: Animals; Gene Expression Regulation, Developmental; Heart; Heart Ventricles; Humans; Mice; Mice, Knockout; Mice, Transgenic; Models, Biological; Myocardium
PubMed: 17205193
DOI: 10.1100/tsw.2006.316 -
Cardiovascular Drugs and Therapy Apr 2019Myocardial slices, also known as "cardiac tissue slices" or "organotypic heart slices," are ultrathin (100-400 μm) slices of living adult ventricular myocardium... (Review)
Review
Myocardial slices, also known as "cardiac tissue slices" or "organotypic heart slices," are ultrathin (100-400 μm) slices of living adult ventricular myocardium prepared using a high-precision vibratome. They are a model of intermediate complexity as they retain the native multicellularity, architecture, and physiology of the heart, while their thinness ensures adequate oxygen and metabolic substrate diffusion in vitro. Myocardial slices can be produced from a variety of animal models and human biopsies, thus providing a representative human in vitro platform for translational cardiovascular research. In this review, we compare myocardial slices to other in vitro models and highlight some of the unique advantages provided by this platform. Additionally, we discuss the work performed in our laboratory to optimize myocardial slice preparation methodology, which resulted in highly viable myocardial slices from both large and small mammalian hearts with only 2-3% cardiomyocyte damage and preserved structure and function. Applications of myocardial slices span both basic and translational cardiovascular science. Our laboratory has utilized myocardial slices for the investigation of cardiac multicellularity, visualizing 3D collagen distribution and micro/macrovascular networks using tissue clearing protocols and investigating the effects of novel conductive biomaterials on cardiac physiology. Myocardial slices have been widely used for pharmacological testing. Finally, the current challenges and future directions for the technology are discussed.
Topics: Animals; Cell Communication; Cell Survival; Humans; In Vitro Techniques; Microtomy; Myocardium; Myocytes, Cardiac; Tissue Survival; Translational Research, Biomedical
PubMed: 30671746
DOI: 10.1007/s10557-019-06853-5 -
Current Opinion in Genetics &... Oct 2013Loss of cardiomyocytes from cardiovascular disease is irreversible and current therapeutic strategies do not redress the loss of myocardium after injury. The discovery... (Review)
Review
Loss of cardiomyocytes from cardiovascular disease is irreversible and current therapeutic strategies do not redress the loss of myocardium after injury. The discovery that endogenous fibroblasts in the heart can be reprogrammed to cardiomyocyte-like cells after myocardial infarction and heart function is improved subsequently has strong implications in bringing this treatment paradigm to the clinic. Here we discuss the advances in direct cardiac reprogramming that will potentially act as a springboard in the generation of effective approaches to restoring cardiac function after injury.
Topics: Animals; Cell Differentiation; Cellular Reprogramming; Fibroblasts; Humans; Mice; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Regeneration
PubMed: 23993230
DOI: 10.1016/j.gde.2013.07.007 -
Developmental Dynamics : An Official... Dec 2016Scientists have studied organs and their development for centuries and, along that path, described models and mechanisms explaining the developmental principles of... (Review)
Review
Scientists have studied organs and their development for centuries and, along that path, described models and mechanisms explaining the developmental principles of organogenesis. In particular, with respect to the heart, new fundamental discoveries are reported continuously that keep changing the way we think about early cardiac development. These discoveries are driven by the need to answer long-standing questions regarding the origin of the earliest cells specified to the cardiac lineage, the differentiation potential of distinct cardiac progenitor cells, and, very importantly, the molecular mechanisms underlying these specification events. As evidenced by numerous examples, the wealth of developmental knowledge collected over the years has had an invaluable impact on establishing efficient strategies to generate cardiovascular cell types ex vivo, from either pluripotent stem cells or via direct reprogramming approaches. The ability to generate functional cardiovascular cells in an efficient and reliable manner will contribute to therapeutic strategies aimed at alleviating the increasing burden of cardiovascular disease and morbidity. Here we will discuss the recent discoveries in the field of cardiac progenitor biology and their translation to the pluripotent stem cell model to illustrate how developmental concepts have instructed regenerative model systems in the past and promise to do so in the future. Developmental Dynamics 245:1130-1144, 2016. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Cell Differentiation; Humans; Myocardium; Myocytes, Cardiac; Pluripotent Stem Cells
PubMed: 27580352
DOI: 10.1002/dvdy.24441 -
Life Sciences Oct 2012The heart possesses a regeneration potential derived from endogenous and exogenous stem and progenitor cell populations, though baseline regeneration appears to be... (Review)
Review
The heart possesses a regeneration potential derived from endogenous and exogenous stem and progenitor cell populations, though baseline regeneration appears to be sub-therapeutic. This limitation was initially attributed to a lack of cells with cardiomyogenic potential following an insult to the myocardium. Rather, recent studies demonstrate increased numbers of cardiomyocyte progenitor cells in diseased hearts. Given that the limiting factor does not appear to be cell quantity but rather repletion of functional cardiomyocytes, it is crucial to understand potential mechanisms inhibiting progenitor cell differentiation. One of the extensively studied areas in heart disease is extracellular matrix (ECM) remodeling, with both the composition and mechanical properties of the ECM undergoing changes in diseased hearts. This review explores the influence of ECM properties on cardiomyogenesis and adult cardiac progenitor cells.
Topics: Animals; Extracellular Matrix; Heart; Heart Diseases; Humans; Myocardium; Myocytes, Cardiac; Regeneration; Stem Cells
PubMed: 22982346
DOI: 10.1016/j.lfs.2012.08.034 -
Science Translational Medicine Jun 2016The promise of cardiac tissue engineering is in the ability to recapitulate in vitro the functional aspects of a healthy heart and disease pathology as well as to design... (Review)
Review
The promise of cardiac tissue engineering is in the ability to recapitulate in vitro the functional aspects of a healthy heart and disease pathology as well as to design replacement muscle for clinical therapy. Parts of this promise have been realized; others have not. In a meeting of scientists in this field, five central challenges or "big questions" were articulated that, if addressed, could substantially advance the current state of the art in modeling heart disease and realizing heart repair.
Topics: Animals; Heart Diseases; Humans; Myocardium; Myocytes, Cardiac; Tissue Engineering
PubMed: 27280684
DOI: 10.1126/scitranslmed.aad2304 -
Circulation Research Jun 2024Immunometabolism is an emerging field at the intersection of immunology and metabolism. Immune cell activation plays a critical role in the pathogenesis of... (Review)
Review
Immunometabolism is an emerging field at the intersection of immunology and metabolism. Immune cell activation plays a critical role in the pathogenesis of cardiovascular diseases and is integral for regeneration during cardiac injury. We currently possess a limited understanding of the processes governing metabolic interactions between immune cells and cardiomyocytes. The impact of this intercellular crosstalk can manifest as alterations to the steady state flux of metabolites and impact cardiac contractile function. Although much of our knowledge is derived from acute inflammatory response, recent work emphasizes heterogeneity and flexibility in metabolism between cardiomyocytes and immune cells during pathological states, including ischemic, cardiometabolic, and cancer-associated disease. Metabolic adaptation is crucial because it influences immune cell activation, cytokine release, and potential therapeutic vulnerabilities. This review describes current concepts about immunometabolic regulation in the heart, focusing on intercellular crosstalk and intrinsic factors driving cellular regulation. We discuss experimental approaches to measure the cardio-immunologic crosstalk, which are necessary to uncover unknown mechanisms underlying the immune and cardiac interface. Deeper insight into these axes holds promise for therapeutic strategies that optimize cardioimmunology crosstalk for cardiac health.
Topics: Humans; Animals; Myocytes, Cardiac; Energy Metabolism; Cardiomyopathies; Myocardium
PubMed: 38843291
DOI: 10.1161/CIRCRESAHA.124.323660 -
Application of Stem Cell Technologies to Regenerate Injured Myocardium and Improve Cardiac Function.Cellular Physiology and Biochemistry :... 2019In the recent decades, cardiovascular diseases emerged as the major leading cause of human mortality. However, current clinical approaches still do not encompass a... (Review)
Review
In the recent decades, cardiovascular diseases emerged as the major leading cause of human mortality. However, current clinical approaches still do not encompass a thorough therapeutic solution for improving heart function of the patients who suffered an extensive myocardial injury. Based on this status quo, stem cells could become a novel option, as a natural source of the new myocardium lineage cells, being capable of paracrine factors secretion, protection or even regeneration of the damaged heart muscle. Efficient stem cell-based therapy of the heart should lead to repair or/and replacement of the degenerated tissue with functional myocardial and endothelial cells. Hereon, various types of pluripotent and multipotent stem cells have been already studied in the pre-clinical and clinical settings, demonstrating their cardiomyogenic and regenerative potential. In this context, as a type of male adult stem/ progenitors, spermatogonial stem cells feature a remarkable ability for a formation of cardiovascular lineages, based on our own observations. Presented data supports the presumption, that spermatogonial stem cells not only have a suitable capacity to generate functional heart cells but can also potentially improve the function of an injured myocardium. In this review article, we first describe the essential molecular and pathophysiological mechanisms involved in the heart tissue injury. Afterwards, based on our ongoing study, we review the impact of the stem cell technologies on the regeneration therapy in cardiovascular and myocardial diseases. Particular emphasis is being put on the usability of spermatogonial stem cells in cardiac therapy.
Topics: Adult Germline Stem Cells; Animals; Cell Differentiation; Heart; Heart Injuries; Humans; Myocardium; Myocytes, Cardiac; Regeneration; Stem Cell Transplantation; Stem Cells
PubMed: 31215778
DOI: 10.33594/000000124 -
Postepy Biochemii Oct 2018The uptake and utilization of energetic substrates in the myocardium are under strict control, any disturbances of which may lead to myocardial dysfunction, such as in... (Review)
Review
The uptake and utilization of energetic substrates in the myocardium are under strict control, any disturbances of which may lead to myocardial dysfunction, such as in the case of ischemia and heart failure. Stearoyl-CoA desaturase (SCD) is an enzyme that converts saturated fatty acids to monounsaturated fatty acids. It is an important player in the regulation of heart metabolism. Our previous studies showed that SCD1 affects substrate utilization by the heart, with a preference for glucose. Large cohort studies established a positive correlation between the plasma fatty acid desaturation index and cardiovascular disease mortality. Therefore, SCD1 might serve as a potential target for future therapies. We review recent findings on the role of SCD1 in the heart, with a focus on cardiac metabolism reprogramming and its involvement in heart dysfunction.
Topics: Cardiovascular Diseases; Fatty Acids; Heart; Humans; Myocardium; Stearoyl-CoA Desaturase
PubMed: 30656903
DOI: 10.18388/pb.2018_130