-
American Journal of Physiology. Heart... Aug 2022The complex and highly organized structural arrangement of some five billion cardiomyocytes directs the coordinated electrical activity and mechanical contraction of the... (Review)
Review
The complex and highly organized structural arrangement of some five billion cardiomyocytes directs the coordinated electrical activity and mechanical contraction of the human heart. The characteristic transmural change in cardiomyocyte orientation underlies base-to-apex shortening, circumferential shortening, and left ventricular torsion during contraction. Individual cardiomyocytes shorten ∼15% and increase in diameter ∼8%. Remarkably, however, the left ventricular wall thickens by up to 30-40%. To accommodate this, the myocardium must undergo significant structural rearrangement during contraction. At the mesoscale, collections of cardiomyocytes are organized into sheetlets, and sheetlet shear is the fundamental mechanism of rearrangement that produces wall thickening. Herein, we review the histological and physiological studies of myocardial mesostructure that have established the sheetlet shear model of wall thickening. Recent developments in tissue clearing techniques allow for imaging of whole hearts at the cellular scale, whereas magnetic resonance imaging (MRI) and computed tomography (CT) can image the myocardium at the mesoscale (100 µm to 1 mm) to resolve cardiomyocyte orientation and organization. Through histology, cardiac diffusion tensor imaging (DTI), and other modalities, mesostructural sheetlets have been confirmed in both animal and human hearts. Recent in vivo cardiac DTI methods have measured reorientation of sheetlets during the cardiac cycle. We also examine the role of pathological cardiac remodeling on sheetlet organization and reorientation, and the impact this has on ventricular function and dysfunction. We also review the unresolved mesostructural questions and challenges that may direct future work in the field.
Topics: Animals; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Heart Ventricles; Myocardial Contraction; Myocardium; Myocytes, Cardiac
PubMed: 35657613
DOI: 10.1152/ajpheart.00059.2022 -
American Journal of Physiology.... Jul 2021Insulin receptors are highly expressed in the heart and vasculature. Insulin signaling regulates cardiac growth, survival, substrate uptake, utilization, and... (Review)
Review
Insulin receptors are highly expressed in the heart and vasculature. Insulin signaling regulates cardiac growth, survival, substrate uptake, utilization, and mitochondrial metabolism. Insulin signaling modulates the cardiac responses to physiological and pathological stressors. Altered insulin signaling in the heart may contribute to the pathophysiology of ventricular remodeling and heart failure progression. Myocardial insulin signaling adapts rapidly to changes in the systemic metabolic milieu. What may initially represent an adaptation to protect the heart from carbotoxicity may contribute to amplifying the risk of heart failure in obesity and diabetes. This review article presents the multiple roles of insulin signaling in cardiac physiology and pathology and discusses the potential therapeutic consequences of modulating myocardial insulin signaling.
Topics: Animals; Cardiomegaly; Diabetes Mellitus; Heart; Heart Failure; Humans; Insulin; Insulin Resistance; Myocardium; Myocytes, Cardiac; Obesity; Receptor, Insulin; Signal Transduction; Ventricular Remodeling
PubMed: 34056923
DOI: 10.1152/ajpendo.00158.2021 -
Biochimica Et Biophysica Acta.... Jun 2020The ketone bodies, d-β-hydroxybutyrate and acetoacetate, are soluble 4-carbon compounds derived principally from fatty acids, that can be metabolised by many oxidative... (Review)
Review
The ketone bodies, d-β-hydroxybutyrate and acetoacetate, are soluble 4-carbon compounds derived principally from fatty acids, that can be metabolised by many oxidative tissues, including heart, in carbohydrate-depleted conditions as glucose-sparing energy substrates. They also have important signalling functions, acting through G-protein coupled receptors and histone deacetylases to regulate metabolism and gene expression including that associated with anti-oxidant activity. Their concentration, and hence availability, increases in diabetes mellitus and heart failure. Whilst known to be substrates for ATP production, especially in starvation, their role(s) in the heart, and in heart disease, is uncertain. Recent evidence, reviewed here, indicates that increased ketone body metabolism is a feature of heart failure, and is accompanied by other changes in substrate selection. Whether the change in myocardial ketone body metabolism is adaptive or maladaptive is unknown, but it offers the possibility of using exogenous ketones to treat the failing heart.
Topics: Acetoacetates; Fatty Acids; Glucose; Heart Failure; Humans; Ketone Bodies; Ketones; Myocardium
PubMed: 32084511
DOI: 10.1016/j.bbadis.2020.165739 -
Basic Research in Cardiology Apr 2022Arrhythmogenic cardiomyopathy (AC) is an inherited disorder characterized by lethal arrhythmias and a risk to sudden cardiac death. A hallmark feature of AC is the... (Review)
Review
Arrhythmogenic cardiomyopathy (AC) is an inherited disorder characterized by lethal arrhythmias and a risk to sudden cardiac death. A hallmark feature of AC is the progressive replacement of the ventricular myocardium with fibro-fatty tissue, which can act as an arrhythmogenic substrate further exacerbating cardiac dysfunction. Therefore, identifying the processes underlying this pathological remodelling would help understand AC pathogenesis and support the development of novel therapies. In this review, we summarize our knowledge on the different models designed to identify the cellular origin and molecular pathways underlying cardiac fibroblast and adipocyte cell differentiation in AC patients. We further outline future perspectives and how targeting the fibro-fatty remodelling process can contribute to novel AC therapeutics.
Topics: Arrhythmias, Cardiac; Cardiomyopathies; Cell Differentiation; Heart Ventricles; Humans; Myocardium
PubMed: 35441328
DOI: 10.1007/s00395-022-00929-4 -
The FEBS Journal Feb 2023Development of the heart, from early morphogenesis to functional maturation, as well as maintenance of its homeostasis are tasks requiring collaborative efforts of... (Review)
Review
Development of the heart, from early morphogenesis to functional maturation, as well as maintenance of its homeostasis are tasks requiring collaborative efforts of cardiac tissue and different extra-cardiac organ systems. The brain, lymphoid organs, and gut are among the interaction partners that can communicate with the heart through a wide array of paracrine signals acting at local or systemic level. Disturbance of cardiac homeostasis following ischemic injury also needs immediate response from these distant organs. Our hearts replace dead muscles with non-contractile fibrotic scars. We have learned from animal models capable of scarless repair that regenerative capability of the heart does not depend only on competency of the myocardium and cardiac-intrinsic factors but also on long-range molecular signals originating in other parts of the body. Here, we provide an overview of inter-organ signals that take part in development and regeneration of the heart. We highlight recent findings and remaining questions. Finally, we discuss the potential of inter-organ modulatory approaches for possible therapeutic use.
Topics: Animals; Myocytes, Cardiac; Regeneration; Myocardium; Paracrine Communication; Models, Animal
PubMed: 34894086
DOI: 10.1111/febs.16319 -
Current Cardiology Reports Dec 2022Heart failure results in the high incidence and mortality all over the world. Mechanical properties of myocardium are critical determinants of cardiac function, with... (Review)
Review
PURPOSE OF REVIEW
Heart failure results in the high incidence and mortality all over the world. Mechanical properties of myocardium are critical determinants of cardiac function, with regional variations in myocardial contractility demonstrated within infarcted ventricles. Quantitative assessment of cardiac contractile function is therefore critical to identify myocardial infarction for the early diagnosis and therapeutic intervention.
RECENT FINDINGS
Current advancement of cardiac functional assessments is in pace with the development of imaging techniques. The methods tailored to advanced imaging have been widely used in cardiac magnetic resonance, echocardiography, and optical microscopy. In this review, we introduce fundamental concepts and applications of representative methods for each imaging modality used in both fundamental research and clinical investigations. All these methods have been designed or developed to quantify time-dependent 2-dimensional (2D) or 3D cardiac mechanics, holding great potential to unravel global or regional myocardial deformation and contractile function from end-systole to end-diastole. Computational methods to assess cardiac contractile function provide a quantitative insight into the analysis of myocardial mechanics during cardiac development, injury, and remodeling.
Topics: Humans; Myocardial Contraction; Diastole; Myocardium; Heart; Systole
PubMed: 36301405
DOI: 10.1007/s11886-022-01814-1 -
Methodist DeBakey Cardiovascular Journal 2023
Topics: Humans; Heart; Myocardium; Regeneration; Myocytes, Cardiac
PubMed: 38028972
DOI: 10.14797/mdcvj.1307 -
Methodist DeBakey Cardiovascular Journal 2023Current therapies for heart failure aim to prevent the deleterious remodeling that occurs after MI injury, but currently no therapies are available to replace lost... (Review)
Review
Current therapies for heart failure aim to prevent the deleterious remodeling that occurs after MI injury, but currently no therapies are available to replace lost cardiomyocytes. Several organisms now being studied are capable of regenerating their myocardium by the proliferation of existing cardiomyocytes. In this review, we summarize the main metabolic pathways of the mammalian heart and how modulation of these metabolic pathways through genetic and pharmacological approaches influences cardiomyocyte proliferation and heart regeneration.
Topics: Animals; Humans; Myocytes, Cardiac; Cell Proliferation; Myocardium; Heart Failure; Cell Cycle; Regeneration; Mammals
PubMed: 38028975
DOI: 10.14797/mdcvj.1309 -
Cells Jul 2022Fibroblasts are stromal cells found in virtually every tissue and organ of the body. For many years, these cells were often considered to be secondary in functional... (Review)
Review
Fibroblasts are stromal cells found in virtually every tissue and organ of the body. For many years, these cells were often considered to be secondary in functional importance to parenchymal cells. Over the past 2 decades, focused research into the roles of fibroblasts has revealed important roles for these cells in the homeostasis of healthy tissue, and has demonstrated that activation of fibroblasts to myofibroblasts is a key step in disease initiation and progression in many tissues, with fibrosis now recognized as not only an outcome of disease, but also a central contributor to tissue dysfunction, particularly in the heart and lungs. With a growing understanding of both fibroblast and myofibroblast heterogeneity, and the deciphering of the humoral and mechanical cues that impact the phenotype of these cells, fibroblast biology is rapidly becoming a major focus in biomedical research. In this review, we provide an overview of fibroblast and myofibroblast biology, particularly in the heart, and including a discussion of pathophysiological processes such as fibrosis and scarring. We then discuss the central role of Canadian researchers in moving this field forwards, particularly in cardiac fibrosis, and highlight some of the major contributions of these individuals to our understanding of fibroblast and myofibroblast biology in health and disease.
Topics: Biology; Canada; Cell Differentiation; Fibroblasts; Fibrosis; Humans; Myocardium
PubMed: 35892569
DOI: 10.3390/cells11152272 -
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