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European Journal of Heart Failure Oct 2013In the last decades it has been appreciated that many patients with heart failure (HF) suffer from HF with preserved ejection fraction (HFpEF). The diagnosis and... (Review)
Review
In the last decades it has been appreciated that many patients with heart failure (HF) suffer from HF with preserved ejection fraction (HFpEF). The diagnosis and treatment of HFpEF is difficult, as we lack specific markers of the disease and no specific treatments have been identified. Galectin-3 has a strong relationship to several aspects of the pathophysiology of HF, especially myocardial fibrosis, the transition from compensated to decompensated HF, and co-morbidities such as renal disease and diabetes. Many of these traits are very commonly observed in patients with HFpEF, and this suggests that galectin-3 may be particularly important and useful in the study of HFpEF. This review summarizes our knowledge of the role of galectin-3 in fibrosis, specifically in experimental models of HF and HFpEF. Galectin-3 may be a marker and also a causal factor, and experimental studies suggested that galectin-3 may be a target for therapy in HFpEF. The detrimental effects of aldosterone may, in part, be conferred via galectin-3, and there are data to suggest that aldosterone blockers are of more benefit in patients with high levels of galectin-3. Furthermore, the relationship of galectin-3 to clinical correlates of developing HFpEF in human subjects is discussed, and the association between increased levels of galectin-3 and new-onset HF and mortality in the general population is highlighted. Additionally, the usefulness of galectin-3 in patients with established HFpEF is described. We conclude that galectin-3 may be useful for early detection, phenotyping, risk stratification, and therapeutic targeting of individuals with early or established HFpEF in which fibrosis is a major contributor to the disease. Finally, we propose areas of further research that should validate the role of galectin-3 in HFpEF.
Topics: Biomarkers; Fibrosis; Galectin 3; Heart Failure; Humans; Myocardium; Stroke Volume
PubMed: 23650131
DOI: 10.1093/eurjhf/hft077 -
Biochimica Et Biophysica Acta Dec 2016O-linked attachment of the monosaccharide β-N-acetyl-glucosamine (O-GlcNAcylation) is a post-translational modification occurring on serine and threonine residues,... (Review)
Review
O-linked attachment of the monosaccharide β-N-acetyl-glucosamine (O-GlcNAcylation) is a post-translational modification occurring on serine and threonine residues, which is evolving as an important mechanism for the regulation of various cellular processes. The present review will, first, provide a general background on the molecular regulation of protein O-GlcNAcylation and will summarize the role of this post-translational modification in various acute cardiac pathologies including ischemia-reperfusion. Then, we will focus on research studies examining protein O-GlcNAcylation in the context of cardiac hypertrophy. A particular emphasis will be laid on the convergent but also divergent actions of O-GlcNAcylation according to the type of hypertrophy investigated, including physiological, pressure overload-induced and diabetes-linked cardiac hypertrophy. In an attempt to distinguish whether O-GlcNAcylation is detrimental or beneficial, this review will present the different O-GlcNAcylated targets involved in hypertrophy development. We will finally argue on potential interest to target O-GlcNAc processes to treat cardiac hypertrophy. This article is part of a Special Issue entitled: The role of post-translational protein modifications on heart and vascular metabolism edited by Jason R.B. Dyck & Jan F.C. Glatz.
Topics: Acylation; Animals; Cardiomegaly; Humans; Muscle Proteins; Myocardium; Protein Processing, Post-Translational
PubMed: 27544701
DOI: 10.1016/j.bbadis.2016.08.012 -
Cell Metabolism Feb 2015The prevalence of heart disease, especially heart failure, continues to increase, and cardiovascular disease remains the leading cause of death worldwide. As... (Review)
Review
The prevalence of heart disease, especially heart failure, continues to increase, and cardiovascular disease remains the leading cause of death worldwide. As cardiomyocytes are essentially irreplaceable, protein quality control is pivotal to cellular homeostasis and, ultimately, cardiac performance. Three evolutionarily conserved mechanisms-autophagy, the unfolded protein response, and the ubiquitin-proteasome system-act in concert to degrade misfolded proteins and eliminate defective organelles. Recent advances have revealed that these mechanisms are intimately associated with cellular metabolism. Going forward, comprehensive understanding of the role of protein quality control mechanisms in cardiac pathology will require integration of metabolic pathways and metabolic control.
Topics: Animals; Heart Diseases; Humans; Myocardium; Proteins
PubMed: 25651176
DOI: 10.1016/j.cmet.2015.01.016 -
Stem Cell Research Nov 2014The critical role that stem cell niches have in cardiac homeostasis and myocardial repair following injury is the focus of this review. Cardiac niches represent... (Review)
Review
The critical role that stem cell niches have in cardiac homeostasis and myocardial repair following injury is the focus of this review. Cardiac niches represent specialized microdomains where the quiescent and activated state of resident stem cells is regulated. Alterations in niche function with aging and cardiac diseases result in abnormal sites of cardiomyogenesis and inadequate myocyte formation. The relevance of Notch1 signaling, gap-junction formation, HIF-1α and metabolic state in the regulation of stem cell growth and differentiation within the cardiac niches are discussed.
Topics: Animals; Heart; Humans; Myocardium; Stem Cell Niche; Stem Cells
PubMed: 25267073
DOI: 10.1016/j.scr.2014.09.001 -
Circulation Research Jan 2015Cardiac myosin-binding protein-C (cMyBP-C) is a thick filament-associated protein that seems to contribute to the regulation of cardiac contraction through interactions... (Review)
Review
Cardiac myosin-binding protein-C (cMyBP-C) is a thick filament-associated protein that seems to contribute to the regulation of cardiac contraction through interactions with either myosin or actin or both. Several studies over the past several years have suggested that the interactions of cardiac myosin-binding protein-C with its binding partners vary with its phosphorylation state, binding predominantly to myosin when dephosphorylated and to actin when it is phosphorylated by protein kinase A or other kinases. Here, we summarize evidence suggesting that phosphorylation of cardiac myosin binding protein-C is a key regulator of the kinetics and amplitude of cardiac contraction during β-adrenergic stimulation and increased stimulus frequency. We propose a model for these effects via a phosphorylation-dependent regulation of the kinetics and extent of cooperative recruitment of cross bridges to the thin filament: phosphorylation of cardiac myosin binding protein-C accelerates cross bridge binding to actin, thereby accelerating recruitment and increasing the amplitude of the cardiac twitch. In contrast, enhanced lusitropy as a result of phosphorylation seems to be caused by a direct effect of phosphorylation to accelerate cross-bridge detachment rate. Depression or elimination of one or both of these processes in a disease, such as end-stage heart failure, seems to contribute to the systolic and diastolic dysfunction that characterizes the disease.
Topics: Animals; Carrier Proteins; Humans; Myocardial Contraction; Myocardium
PubMed: 25552695
DOI: 10.1161/CIRCRESAHA.116.300561 -
International Journal of Molecular... May 2024Cardiac fibrosis, a process characterized by excessive extracellular matrix (ECM) deposition, is a common pathological consequence of many cardiovascular diseases (CVDs)... (Review)
Review
Cardiac fibrosis, a process characterized by excessive extracellular matrix (ECM) deposition, is a common pathological consequence of many cardiovascular diseases (CVDs) normally resulting in organ failure and death. Cardiac fibroblasts (CFs) play an essential role in deleterious cardiac remodeling and dysfunction. In response to injury, quiescent CFs become activated and adopt a collagen-secreting phenotype highly contributing to cardiac fibrosis. In recent years, studies have been focused on the exploration of molecular and cellular mechanisms implicated in the activation process of CFs, which allow the development of novel therapeutic approaches for the treatment of cardiac fibrosis. Transcriptomic analyses using single-cell RNA sequencing (RNA-seq) have helped to elucidate the high cellular diversity and complex intercellular communication networks that CFs establish in the mammalian heart. Furthermore, a significant body of work supports the critical role of epigenetic regulation on the expression of genes involved in the pathogenesis of cardiac fibrosis. The study of epigenetic mechanisms, including DNA methylation, histone modification, and chromatin remodeling, has provided more insights into CF activation and fibrotic processes. Targeting epigenetic regulators, especially DNA methyltransferases (DNMT), histone acetylases (HAT), or histone deacetylases (HDAC), has emerged as a promising approach for the development of novel anti-fibrotic therapies. This review focuses on recent transcriptomic advances regarding CF diversity and molecular and epigenetic mechanisms that modulate the activation process of CFs and their possible clinical applications for the treatment of cardiac fibrosis.
Topics: Epigenesis, Genetic; Humans; Fibrosis; Animals; Fibroblasts; Myocardium; DNA Methylation
PubMed: 38892192
DOI: 10.3390/ijms25116004 -
Circulation Research Jun 2024Heart failure (HF) is characterized by a progressive decline in cardiac function and represents one of the largest health burdens worldwide. Clinically, 2 major types of... (Review)
Review
Heart failure (HF) is characterized by a progressive decline in cardiac function and represents one of the largest health burdens worldwide. Clinically, 2 major types of HF are distinguished based on the left ventricular ejection fraction (EF): HF with reduced EF and HF with preserved EF. While both types share several risk factors and features of adverse cardiac remodeling, unique hallmarks beyond ejection fraction that distinguish these etiologies also exist. These differences may explain the fact that approved therapies for HF with reduced EF are largely ineffective in patients suffering from HF with preserved EF. Improving our understanding of the distinct cellular and molecular mechanisms is crucial for the development of better treatment strategies. This article reviews the knowledge of the immunologic mechanisms underlying HF with reduced and preserved EF and discusses how the different immune profiles elicited may identify attractive therapeutic targets for these conditions. We review the literature on the reported mechanisms of adverse cardiac remodeling in HF with reduced and preserved EF, as well as the immune mechanisms involved. We discuss how the knowledge gained from preclinical models of the complex syndrome of HF as well as from clinical data obtained from patients may translate to a better understanding of HF and result in specific treatments for these conditions in humans.
Topics: Humans; Heart Failure; Stroke Volume; Animals; Ventricular Remodeling; Myocarditis; Ventricular Function, Left; Myocardium
PubMed: 38843295
DOI: 10.1161/CIRCRESAHA.124.323659 -
JACC. Cardiovascular Imaging Jan 2009
Review
Topics: Aged, 80 and over; Animals; Biomarkers; Cardiovascular Diseases; Diagnostic Imaging; Disease Models, Animal; Female; Heart Function Tests; Humans; Myocardium; Predictive Value of Tests; Prognosis
PubMed: 19356541
DOI: 10.1016/j.jcmg.2008.11.001 -
Nuclear Medicine Review. Central &... Apr 2012Accurate identification of viable myocardium is crucial in patient qualification for medical or surgical treatment. Only persons with confirmed cardiac viability will... (Review)
Review
Accurate identification of viable myocardium is crucial in patient qualification for medical or surgical treatment. Only persons with confirmed cardiac viability will benefit from revascularization procedures. It is also well known, that the amount of viable myocardium assessed preoperatively is the best indicator of long term cardiac event free survival after cardiac intervention.There are several diagnostic approaches used in current clinical practice for assessment of myocardial viability. Analysis of wall thickness or myocardial contraction, evaluation of cardiac perfusion or metabolism can be assessed using following modalities: Echocardiography, Cardiac Molecular Imaging techniques (PET, SPECT), Cardiovascular MR or Cardiovascular CT. The article describes the methods and problems of viability assessment in 18FDG PET study. PET imaging has proved its accuracy and reproducibility for myocardial ischemia and viability assessment. However this unique in its ability for showing the particular substrate metabolism technique has unfortunately some disadvantages: currently achieved PET resolution is 0.4 cm. However the combined devices multislice computed tomography scanners with PET (PET/CT) are now widely used in clinical practice. This combination allows for wider morphologic assessments: coronary calcium scoring and non-invasive coronary angiography may be added to myocardial perfusion/metabolic imaging if necessary.
Topics: Disease; Fluorodeoxyglucose F18; Heart; Humans; Multimodal Imaging; Myocardium; Positron-Emission Tomography; Tissue Survival; Tomography, X-Ray Computed
PubMed: 23047574
DOI: 10.5603/nmr-18731 -
Acta Biomaterialia Apr 2018Bioengineering of a functional cardiac tissue composed of primary cardiomyocytes has great potential for myocardial regeneration and in vitro tissue modeling. However,...
UNLABELLED
Bioengineering of a functional cardiac tissue composed of primary cardiomyocytes has great potential for myocardial regeneration and in vitro tissue modeling. However, its applications remain limited because the cardiac tissue is a highly organized structure with unique physiologic, biomechanical, and electrical properties. In this study, we undertook a proof-of-concept study to develop a contractile cardiac tissue with cellular organization, uniformity, and scalability by using three-dimensional (3D) bioprinting strategy. Primary cardiomyocytes were isolated from infant rat hearts and suspended in a fibrin-based bioink to determine the priting capability for cardiac tissue engineering. This cell-laden hydrogel was sequentially printed with a sacrificial hydrogel and a supporting polymeric frame through a 300-µm nozzle by pressured air. Bioprinted cardiac tissue constructs had a spontaneous synchronous contraction in culture, implying in vitro cardiac tissue development and maturation. Progressive cardiac tissue development was confirmed by immunostaining for α-actinin and connexin 43, indicating that cardiac tissues were formed with uniformly aligned, dense, and electromechanically coupled cardiac cells. These constructs exhibited physiologic responses to known cardiac drugs regarding beating frequency and contraction forces. In addition, Notch signaling blockade significantly accelerated development and maturation of bioprinted cardiac tissues. Our results demonstrated the feasibility of bioprinting functional cardiac tissues that could be used for tissue engineering applications and pharmaceutical purposes.
STATEMENT OF SIGNIFICANCE
Cardiovascular disease remains a leading cause of death in the United States and a major health-care burden. Myocardial infarction (MI) is a main cause of death in cardiovascular diseases. MI occurs as a consequence of sudden blocking of blood vessels supplying the heart. When occlusions in the coronary arteries occur, an immediate decrease in nutrient and oxygen supply to the cardiac muscle, resulting in permanent cardiac cell death. Eventually, scar tissue formed in the damaged cardiac muscle that cannot conduct electrical or mechanical stimuli thus leading to a reduction in the pumping efficiency of the heart. The therapeutic options available for end-stage heart failure is to undergo heart transplantation or the use of mechanical ventricular assist devices (VADs). However, many patients die while being on a waiting list, due to the organ shortage and limitation of VADs, such as surgical complications, infection, thrombogenesis, and failure of the electrical motor and hemolysis. Ultimately, 3D bioprinting strategy aims to create clinically applicable tissue constructs that can be immediately implanted in the body. To date, the focus on replicating complex and heterogeneous tissue constructs continues to increase as 3D bioprinting technologies advance. In this study, we demonstrated the feasibility of 3D bioprinting strategy to bioengineer the functional cardiac tissue that possesses a highly organized structure with unique physiological and biomechanical properties similar to native cardiac tissue. This bioprinting strategy has great potential to precisely generate functional cardiac tissues for use in pharmaceutical and regenerative medicine applications.
Topics: Animals; Bioprinting; Hydrogels; Myocardial Contraction; Myocardium; Myocytes, Cardiac; Printing, Three-Dimensional; Rats; Rats, Sprague-Dawley; Tissue Engineering
PubMed: 29452273
DOI: 10.1016/j.actbio.2018.02.007