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Biology Open Sep 2021Well-orchestrated intercellular communication networks are pivotal to maintaining cardiac homeostasis and to ensuring adaptative responses and repair after injury.... (Review)
Review
Well-orchestrated intercellular communication networks are pivotal to maintaining cardiac homeostasis and to ensuring adaptative responses and repair after injury. Intracardiac communication is sustained by cell-cell crosstalk, directly via gap junctions (GJ) and tunneling nanotubes (TNT), indirectly through the exchange of soluble factors and extracellular vesicles (EV), and by cell-extracellular matrix (ECM) interactions. GJ-mediated communication between cardiomyocytes and with other cardiac cell types enables electrical impulse propagation, required to sustain synchronized heart beating. In addition, TNT-mediated organelle transfer has been associated with cardioprotection, whilst communication via EV plays diverse pathophysiological roles, being implicated in angiogenesis, inflammation and fibrosis. Connecting various cell populations, the ECM plays important functions not only in maintaining the heart structure, but also acting as a signal transducer for intercellular crosstalk. Although with distinct etiologies and clinical manifestations, intercellular communication derailment has been implicated in several cardiac disorders, including myocardial infarction and hypertrophy, highlighting the importance of a comprehensive and integrated view of complex cell communication networks. In this review, I intend to provide a critical perspective about the main mechanisms contributing to regulate cellular crosstalk in the heart, which may be considered in the development of future therapeutic strategies, using cell-based therapies as a paradigmatic example. This Review has an associated Future Leader to Watch interview with the author.
Topics: Cell Communication; Cell Membrane Structures; Extracellular Matrix; Gap Junctions; Heart Diseases; Humans; Myocardium; Myocytes, Cardiac; Nanotubes
PubMed: 34494646
DOI: 10.1242/bio.058777 -
Cardiovascular Drugs and Therapy Apr 2020Current cardiovascular magnetic resonance imaging techniques provide an exquisite assessment of the structure and function of the heart and great vessels, but their... (Review)
Review
Current cardiovascular magnetic resonance imaging techniques provide an exquisite assessment of the structure and function of the heart and great vessels, but their ability to assess the molecular processes that underpin changes in cardiac function in health and disease is limited by inherent insensitivity. Hyperpolarized magnetic resonance is a new technology which overcomes this limitation, generating molecular contrast agents with an improvement in magnetic resonance signal of up to five orders of magnitude. One key molecule, hyperpolarized [1-C]pyruvate, shows particular promise for the assessment of cardiac energy metabolism and other fundamental biological processes in cardiovascular disease. This molecule has numerous potential applications of clinical relevance and has now been translated to human use in early clinical studies. This review outlines the principles of hyperpolarized magnetic resonance and key potential cardiovascular applications for this new technology. Finally, we provide an overview of the pipeline for forthcoming hyperpolarized agents and their potential applications in cardiovascular disease.
Topics: Animals; Carbon Isotopes; Cardiovascular Diseases; Contrast Media; Energy Metabolism; Humans; Magnetic Resonance Imaging; Myocardium; Predictive Value of Tests; Pyruvic Acid; Tissue Survival
PubMed: 32020468
DOI: 10.1007/s10557-020-06942-w -
International Journal of Molecular... Oct 2023Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and the leading cause of sudden cardiac death in young people. Mutations in genes that... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and the leading cause of sudden cardiac death in young people. Mutations in genes that encode structural proteins of the cardiac sarcomere are the more frequent genetic cause of HCM. The disease is characterized by cardiomyocyte hypertrophy and myocardial fibrosis, which is defined as the excessive deposition of extracellular matrix proteins, mainly collagen I and III, in the myocardium. The development of fibrotic tissue in the heart adversely affects cardiac function. In this review, we discuss the latest evidence on how cardiac fibrosis is promoted, the role of cardiac fibroblasts, their interaction with cardiomyocytes, and their activation via the TGF-β pathway, the primary intracellular signalling pathway regulating extracellular matrix turnover. Finally, we summarize new findings on profibrotic genes as well as genetic and non-genetic factors involved in the pathophysiology of HCM.
Topics: Humans; Adolescent; Cardiomyopathy, Hypertrophic; Myocardium; Myocytes, Cardiac; Fibroblasts; Fibrosis
PubMed: 37834293
DOI: 10.3390/ijms241914845 -
Circulation. Cardiovascular Imaging Nov 2023Infiltrative cardiomyopathies comprise a broad spectrum of inherited or acquired conditions caused by deposition of abnormal substances within the myocardium. Increased... (Review)
Review
Infiltrative cardiomyopathies comprise a broad spectrum of inherited or acquired conditions caused by deposition of abnormal substances within the myocardium. Increased wall thickness, inflammation, microvascular dysfunction, and fibrosis are the common pathological processes that lead to abnormal myocardial filling, chamber dilation, and disruption of conduction system. Advanced disease presents as heart failure and cardiac arrhythmias conferring poor prognosis. Infiltrative cardiomyopathies are often diagnosed late or misclassified as other more common conditions, such as hypertrophic cardiomyopathy, hypertensive heart disease, ischemic or other forms of nonischemic cardiomyopathies. Accurate diagnosis is also critical because clinical features, testing methodologies, and approach to treatment vary significantly even within the different types of infiltrative cardiomyopathies on the basis of the type of substance deposited. Substantial advances in noninvasive cardiac imaging have enabled accurate and early diagnosis. thereby eliminating the need for endomyocardial biopsy in most cases. This scientific statement discusses the role of contemporary multimodality imaging of infiltrative cardiomyopathies, including echocardiography, nuclear and cardiac magnetic resonance imaging in the diagnosis, prognostication, and assessment of response to treatment.
Topics: Humans; American Heart Association; Cardiomyopathies; Heart; Heart Failure; Myocardium; Magnetic Resonance Imaging
PubMed: 37916407
DOI: 10.1161/HCI.0000000000000081 -
Molecular Aspects of Medicine Oct 2023Heart failure is a leading cause of mortality and hospitalization worldwide. Cardiac fibrosis, resulting from the excessive deposition of collagen fibers, is a common... (Review)
Review
Heart failure is a leading cause of mortality and hospitalization worldwide. Cardiac fibrosis, resulting from the excessive deposition of collagen fibers, is a common feature across the spectrum of conditions converging in heart failure. Eventually, either reparative or reactive in nature, in the long-term cardiac fibrosis contributes to heart failure development and progression and is associated with poor clinical outcomes. Despite this, specific cardiac antifibrotic therapies are lacking, making cardiac fibrosis an urgent unmet medical need. In this context, a better patient phenotyping is needed to characterize the heterogenous features of cardiac fibrosis to advance toward its personalized management. In this review, we will describe the different phenotypes associated with cardiac fibrosis in heart failure and we will focus on the potential usefulness of imaging techniques and circulating biomarkers for the non-invasive characterization and phenotyping of this condition and for tracking its clinical impact. We will also recapitulate the cardiac antifibrotic effects of existing heart failure and non-heart failure drugs and we will discuss potential strategies under preclinical development targeting the activation of cardiac fibroblasts at different levels, as well as targeting additional extracardiac processes.
Topics: Humans; Myocardium; Heart Failure; Fibroblasts; Biomarkers; Fibrosis
PubMed: 37384998
DOI: 10.1016/j.mam.2023.101194 -
Frontiers in Immunology 2023Acute myocardial infarction (MI) is a prevalent and highly fatal global disease. Despite significant reduction in mortality rates with standard treatment regimens, the... (Review)
Review
Acute myocardial infarction (MI) is a prevalent and highly fatal global disease. Despite significant reduction in mortality rates with standard treatment regimens, the risk of heart failure (HF) remains high, necessitating innovative approaches to protect cardiac function and prevent HF progression. Cardiac resident macrophages (cMacs) have emerged as key regulators of the pathophysiology following MI. cMacs are a heterogeneous population composed of subsets with different lineage origins and gene expression profiles. Several critical aspects of post-MI pathophysiology have been shown to be regulated by cMacs, including recruitment of peripheral immune cells, clearance and replacement of damaged myocardial cells. Furthermore, cMacs play a crucial role in regulating cardiac fibrosis, risk of arrhythmia, energy metabolism, as well as vascular and lymphatic remodeling. Given the multifaceted roles of cMacs in post-MI pathophysiology, targeting cMacs represents a promising therapeutic strategy. Finally, we discuss novel treatment strategies, including using nanocarriers to deliver drugs to cMacs or using cell therapies to introduce exogenous protective cMacs into the heart.
Topics: Humans; Myocardium; Myocardial Infarction; Myocytes, Cardiac; Macrophages; Heart Failure
PubMed: 37457720
DOI: 10.3389/fimmu.2023.1207100 -
Blood Sep 2022
Topics: Anemia, Sickle Cell; Biomarkers; Cardiomyopathies; Fibrosis; Humans; Myocardium
PubMed: 36107457
DOI: 10.1182/blood.2022017725 -
Arteriosclerosis, Thrombosis, and... May 2024
Review
Topics: Lymphangiogenesis; Humans; Animals; Lymphatic Vessels; Cardiovascular Diseases; Signal Transduction; Myocardium
PubMed: 38657034
DOI: 10.1161/ATVBAHA.123.319572 -
Journal of Molecular and Cellular... Aug 2023Heart disease continues to be the leading cause of mortality worldwide, primarily attributed to the restricted regenerative potential of the adult human heart following... (Review)
Review
Heart disease continues to be the leading cause of mortality worldwide, primarily attributed to the restricted regenerative potential of the adult human heart following injury. In contrast to their adult counterparts, many neonatal mammals can spontaneously regenerate their myocardium in the first few days of life via extensive proliferation of the pre-existing cardiomyocytes. Reasons for the decline in regenerative capacity during postnatal development, and how to control it, remain largely unexplored. Accumulated evidence suggests that the preservation of regenerative potential depends on a conducive metabolic state in the embryonic and neonatal heart. Along with the postnatal increase in oxygenation and workload, the mammalian heart undergoes a metabolic transition, shifting its primary metabolic substrate from glucose to fatty acids shortly after birth for energy advantage. This metabolic switch causes cardiomyocyte cell-cycle arrest, which is widely regarded as a key mechanism for the loss of regenerative capacity. Beyond energy provision, emerging studies have suggested a link between this intracellular metabolism dynamics and postnatal epigenetic remodeling of the mammalian heart that reshapes the expression of many genes important for cardiomyocyte proliferation and cardiac regeneration, since many epigenetic enzymes utilize kinds of metabolites as obligate cofactors or substrates. This review summarizes the current state of knowledge of metabolism and metabolite-mediated epigenetic modifications in cardiomyocyte proliferation, with a particular focus on highlighting the potential therapeutic targets that hold promise to treat human heart failure via metabolic and epigenetic regulations.
Topics: Animals; Infant, Newborn; Adult; Humans; Myocytes, Cardiac; Heart; Myocardium; Heart Diseases; Epigenesis, Genetic; Cell Proliferation; Mammals
PubMed: 37331466
DOI: 10.1016/j.yjmcc.2023.06.002 -
American Journal of Physiology. Heart... Mar 2024Cardiac arrhythmias commonly occur as a result of aberrant electrical impulse formation or conduction in the myocardium. Frequently discussed triggers include underlying... (Review)
Review
Cardiac arrhythmias commonly occur as a result of aberrant electrical impulse formation or conduction in the myocardium. Frequently discussed triggers include underlying heart diseases such as myocardial ischemia, electrolyte imbalances, or genetic anomalies of ion channels involved in the tightly regulated cardiac action potential. Recently, the role of innate immune cells in the onset of arrhythmic events has been highlighted in numerous studies, correlating leukocyte expansion in the myocardium to increased arrhythmic burden. Here, we aim to call attention to the role of neutrophils in the pathogenesis of cardiac arrhythmias and their expansion during myocardial ischemia and infectious disease manifestation. In addition, we will elucidate molecular mechanisms associated with neutrophil activation and discuss their involvement as direct mediators of arrhythmogenicity.
Topics: Humans; Heart Conduction System; Neutrophils; Arrhythmias, Cardiac; Myocardium; Myocardial Ischemia
PubMed: 38099844
DOI: 10.1152/ajpheart.00590.2023