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Pharmacological Research Jul 2024Inflammation is a crucial factor in cardiac remodeling after acute myocardial infarction (MI). Neutrophils, as the first wave of leukocytes to infiltrate the injured... (Review)
Review
Inflammation is a crucial factor in cardiac remodeling after acute myocardial infarction (MI). Neutrophils, as the first wave of leukocytes to infiltrate the injured myocardium, exacerbate inflammation and cardiac injury. However, therapies that deplete neutrophils to manage cardiac remodeling after MI have not consistently produced promising outcomes. Recent studies have revealed that neutrophils at different time points and locations may have distinct functions. Thus, transferring neutrophil phenotypes, rather than simply blocking their activities, potentially meet the needs of cardiac repair. In this review, we focus on discussing the fate, heterogeneity, functions of neutrophils, and attempt to provide a more comprehensive understanding of their roles and targeting strategies in MI. We highlight the strategies and translational potential of targeting neutrophils to limit cardiac injury to reduce morbidity and mortality from MI.
Topics: Humans; Myocardial Infarction; Neutrophils; Animals; Myocardium
PubMed: 38866263
DOI: 10.1016/j.phrs.2024.107256 -
Philosophical Transactions. Series A,... Jun 2020Models of electrical activation and recovery in cardiac cells and tissue have become valuable research tools, and are beginning to be used in safety-critical... (Review)
Review
Models of electrical activation and recovery in cardiac cells and tissue have become valuable research tools, and are beginning to be used in safety-critical applications including guidance for clinical procedures and for drug safety assessment. As a consequence, there is an urgent need for a more detailed and quantitative understanding of the ways that uncertainty and variability influence model predictions. In this paper, we review the sources of uncertainty in these models at different spatial scales, discuss how uncertainties are communicated across scales, and begin to assess their relative importance. We conclude by highlighting important challenges that continue to face the cardiac modelling community, identifying open questions, and making recommendations for future studies. This article is part of the theme issue 'Uncertainty quantification in cardiac and cardiovascular modelling and simulation'.
Topics: Electrophysiological Phenomena; Heart; Humans; Models, Cardiovascular; Myocardium; Uncertainty
PubMed: 32448070
DOI: 10.1098/rsta.2019.0335 -
The Journal of Biological Chemistry Mar 2011During the last 15 years, the perception of the cardiac z-disc has undergone substantial changes. Initially viewed as a structural component at the lateral boundaries of... (Review)
Review
During the last 15 years, the perception of the cardiac z-disc has undergone substantial changes. Initially viewed as a structural component at the lateral boundaries of the sarcomere, the cardiac z-disc has increasingly become recognized as a nodal point in cardiomyocyte signal transduction and disease. This minireview thus focuses on novel components and recent developments in z-disc biology and their role in cardiac signaling and disease.
Topics: Animals; Heart Diseases; Humans; Myocardium; Myocytes, Cardiac; Sarcomeres; Signal Transduction
PubMed: 21257757
DOI: 10.1074/jbc.R110.174268 -
Journal of Cardiovascular Translational... Aug 2011Pathology in the heart can be examined at several scales, ranging from the molecular to the macroscopic. Traditionally, fluorescence-based techniques such as flow... (Review)
Review
Pathology in the heart can be examined at several scales, ranging from the molecular to the macroscopic. Traditionally, fluorescence-based techniques such as flow cytometry have been used to study the myocardium at the molecular, cellular, and microscopic levels. Recent advances in magnetic resonance imaging (MRI), however, have made it possible to image certain cellular and molecular events in the myocardium noninvasively in vivo. In addition, diffusion MRI has been used to image myocardial fiber architecture and microstructure in the intact heart. Diffusion MRI tractography, in particular, is providing novel insights into myocardial microsctructure in both health and disease. Recent developments have also been made in fluorescence imaging, making it possible to image fluorescent probes in the heart of small animals noninvasively in vivo. Moreover, techniques have been developed to perform in vivo fluorescence tomography of the mouse heart. These advances in MRI and fluorescence imaging allow events in the myocardium to be imaged at several scales linking molecular changes to alterations in microstructure and microstructural changes to gross function. A complete and integrated picture of pathophysiology in the myocardium is thus obtained. This multiscale approach has the potential to be of significant value not only in preclinical research but, ultimately, in the clinical arena as well.
Topics: Animals; Diffusion Magnetic Resonance Imaging; Heart Diseases; Humans; Microscopy, Fluorescence; Molecular Imaging; Myocardium
PubMed: 21643889
DOI: 10.1007/s12265-011-9284-0 -
Nature Reviews. Cardiology Oct 2018Despite substantial recent advances, regeneration of the damaged human heart is still an unmet ambition. By extracting our current knowledge from developmental biology,...
Despite substantial recent advances, regeneration of the damaged human heart is still an unmet ambition. By extracting our current knowledge from developmental biology, animal models of heart regeneration, and clinical observations, we propose five hallmarks of cardiac regeneration and suggest a holistic approach to reconstituting human heart function.
Topics: Animals; Fibrosis; Heart Diseases; Humans; Muscle Development; Myocardium; Neovascularization, Physiologic; Recovery of Function; Regenerative Medicine; Treatment Outcome; Ventricular Remodeling
PubMed: 30190531
DOI: 10.1038/s41569-018-0079-8 -
Journal of Molecular Medicine (Berlin,... Aug 2015Cardiac fibroblasts are a major cell population of the heart and are characterized by their capacity to produce extracellular matrix (ECM). In hearts subjected to... (Review)
Review
Cardiac fibroblasts are a major cell population of the heart and are characterized by their capacity to produce extracellular matrix (ECM). In hearts subjected to pressure overload, excessive fibroblast accumulation is responsible for fibrosis of the myocardium, a major clinical issue. Hence, understanding mechanisms generating fibroblasts in this context has become a key question in the cardiovascular field. Recent studies now point to the activation of resident fibroblasts as the underlying cause of fibrosis. However, de novo generation of fibroblasts from endothelium and circulating hematopoietic cells has also been proposed to significantly contribute to fibrosis. Here, we discuss the latest findings on fibroblast origins, with a particular emphasis on the pressure overload model, and the implication of these findings for the development of anti-fibrotic therapies that are currently lacking.
Topics: Animals; Extracellular Matrix; Fibroblasts; Fibrosis; Heart; Heart Failure; Humans; Myocardium
PubMed: 26169532
DOI: 10.1007/s00109-015-1314-y -
Progress in Biophysics and Molecular... 2012Certain forms of heart disease involve gross morphological changes to the myocardium that alter its hemodynamic loading conditions. These changes can ultimately lead to... (Review)
Review
Certain forms of heart disease involve gross morphological changes to the myocardium that alter its hemodynamic loading conditions. These changes can ultimately lead to the increased deposition of extracellular matrix (ECM) proteins, such as collagen and fibronectin, which together work to pathologically alter the myocardium's bulk tissue mechanics. In addition to changing the mechanical properties of the heart, this maladaptive remodeling gives rise to changes in myocardium electrical conductivity and synchrony since the tissue's mechanical properties are intimately tied to its electrical characteristics. This phenomenon, called mechanoelectrical coupling (MEC), can render individuals affected by heart disease arrhythmogenic and susceptible to Sudden Cardiac Death (SCD). The underlying mechanisms of MEC have been attributed to various processes, including the action of stretch activated channels and changes in troponin C-Ca(2+) binding affinity. However, changes in the heart post infarction or due to congenital myopathies are also accompanied by shifts in the expression of various molecular components of cardiomyocytes, including the mechanosensitive family of integrin proteins. As transmembrane proteins, integrins mechanically couple the ECM with the intracellular cytoskeleton and have been implicated in mediating ion homeostasis in various cell types, including neurons and smooth muscle. Given evidence of altered integrin expression in the setting of heart disease coupled with the associated increased risk for arrhythmia, we argue in this review that integrin signaling contributes to MEC. In light of the significant mortality associated with arrhythmia and SCD, close examination of all culpable mechanisms, including integrin-mediated MEC, is necessary.
Topics: Animals; Electrophysiological Phenomena; Feedback; Humans; Integrins; Mechanical Phenomena; Myocardium; Signal Transduction
PubMed: 22819851
DOI: 10.1016/j.pbiomolbio.2012.07.002 -
Life Sciences Mar 2014Myocardial ischemia/reperfusion (I/R) is the most common cause of myocardial inflammation, which is primarily a manifestation of the innate immune responses. Innate... (Review)
Review
Myocardial ischemia/reperfusion (I/R) is the most common cause of myocardial inflammation, which is primarily a manifestation of the innate immune responses. Innate immunity is activated when pattern recognition receptors (PRRs) respond to molecular patterns common to microbes and to danger signals expressed by injured or infected cells, so called pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The expression of various PRRs in cardiomyocytes and the release of DAMPs from cardiomyocytes subjected to I/R injury, through active mechanisms as well as passive processes, enable cardiomyocytes to generate innate immune responses. Studies in isolated heart and cardiomyocytes have confirmed the inflammatory and functional effects of cardiac PRRs especially Toll-like receptors in response to I/R-derived DAMPs, such as heat shock proteins. This review addresses the active role of cardiomyocytes in mediating innate inflammatory responses to myocardial I/R. We propose that cardiomyocytes act as innate immune cells in myocardial I/R injury.
Topics: Animals; HMGB1 Protein; Heat-Shock Proteins; Humans; Immunity, Innate; Lectins, C-Type; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; Nod Signaling Adaptor Proteins; Toll-Like Receptors
PubMed: 24486305
DOI: 10.1016/j.lfs.2014.01.062 -
Cells Mar 2021The development of stem-cell-based and regenerative therapies for cardiovascular and other diseases has faced an unexpected roadblock in clinical translation [...].
The development of stem-cell-based and regenerative therapies for cardiovascular and other diseases has faced an unexpected roadblock in clinical translation [...].
Topics: Cell Differentiation; Cellular Senescence; Humans; Immunity, Innate; Interdisciplinary Research; Myocardium; Myocytes, Cardiac; Regeneration; Regenerative Medicine; Stem Cell Transplantation; Stem Cells
PubMed: 33800252
DOI: 10.3390/cells10030592 -
BioMed Research International 2014Left ventricle hypertrophy is a common outcome of pressure overload stimulus closely associated with hypertension. This process is triggered by adverse molecular... (Review)
Review
Left ventricle hypertrophy is a common outcome of pressure overload stimulus closely associated with hypertension. This process is triggered by adverse molecular signalling, gene expression, and proteome alteration. Proteomic research has revealed that several molecular targets are associated with pathologic cardiac hypertrophy, including angiotensin II, endothelin-1 and isoproterenol. Several metabolic, contractile, and stress-related proteins are shown to be altered in cardiac hypertrophy derived by hypertension. On the other hand, exercise is a nonpharmacologic agent used for hypertension treatment, where cardiac hypertrophy induced by exercise training is characterized by improvement in cardiac function and resistance against ischemic insult. Despite the scarcity of proteomic research performed with exercise, healthy and pathologic heart proteomes are shown to be modulated in a completely different way. Hence, the altered proteome induced by exercise is mostly associated with cardioprotective aspects such as contractile and metabolic improvement and physiologic cardiac hypertrophy. The present review, therefore, describes relevant studies involving the molecular characteristics and alterations from hypertensive-induced and exercise-induced hypertrophy, as well as the main proteomic research performed in this field. Furthermore, proteomic research into the effect of hypertension on other target-demerged organs is examined.
Topics: Animals; Exercise; Humans; Hypertension; Muscle Proteins; Myocardium; Proteome
PubMed: 24877123
DOI: 10.1155/2014/634132