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Development (Cambridge, England) Jul 2020The valves of the heart are crucial for ensuring that blood flows in one direction from the heart, through the lungs and back to the rest of the body. Heart valve... (Review)
Review
The valves of the heart are crucial for ensuring that blood flows in one direction from the heart, through the lungs and back to the rest of the body. Heart valve development is regulated by complex interactions between different cardiac cell types and is subject to blood flow-driven forces. Recent work has begun to elucidate the important roles of developmental pathways, valve cell heterogeneity and hemodynamics in determining the structure and function of developing valves. Furthermore, this work has revealed that many key genetic pathways involved in cardiac valve development are also implicated in diseased valves. Here, we review recent discoveries that have furthered our understanding of the molecular, cellular and mechanosensitive mechanisms of valve development, and highlight new insights into congenital and acquired valve disease.
Topics: Animals; Gene Expression Regulation, Developmental; Heart Valve Diseases; Heart Valves; Hemodynamics; Humans
PubMed: 32620577
DOI: 10.1242/dev.183020 -
Circulation Research Apr 2019EndMT is an intricate cellular differentiation process whereby endothelial cells detach and migrate away from the endothelium and, to varying extents, decrease... (Review)
Review
EndMT is an intricate cellular differentiation process whereby endothelial cells detach and migrate away from the endothelium and, to varying extents, decrease endothelial properties and acquire mesenchymal features. First described in developing heart valves as an epithelial mesenchymal transformation, EndMT begins in response to an external signal, often transforming growth factor-β (TGFβ). The endothelial cells lose luminal-abluminal polarity, extend filopodia and migrate into extravascular space where they take up residence, in the case of heart valves, as valve interstitial cells. Properly controlled EndMT is essential for heart valve development: too little and valves fail to form; too much and the valves thicken and cannot close properly. EndMT appears to persist past embryonic development as endothelial cells expressing EndMT markers can be detected in adult ovine and human valves. , valve endothelial cells treated with TGFβ undergo robust EndMT; hence valve endothelial cells can serve as a prototype for revealing regulators of EndMT. Reactivation of EndMT in post-natal settings has emerged as a potential mechanism for adaptation to new physiologic settings and at the same time for maladaptive responses to disease. This is exemplified by EndMT in cardiac valves, which are lined with a specialized endothelium that originates from FLK1+ (a.k.a. VEGFR2+) progenitor cells in cardiac mesoderm, distinct from vascular endothelium. Although endocardial and vascular endothelium are molecularly similar, endocardial endothelial cells exhibit a distinct plasticity, which may provide valve endothelial cells with unique capabilities for adaptation and function over a lifetime.
Topics: Age Factors; Animals; Cardiovascular Diseases; Cell Movement; Endothelial Cells; Epithelial-Mesenchymal Transition; Extracellular Matrix; Heart Valves; Leukocyte Common Antigens; Mice; Mitral Valve; Mitral Valve Insufficiency; Models, Animal; Myocardial Infarction; Neovascularization, Physiologic; Sheep; Stress, Physiological; Transforming Growth Factor beta
PubMed: 30973806
DOI: 10.1161/CIRCRESAHA.119.314813 -
The Journal of International Medical... Jul 2022Complications of heart valve surgery lead to physical inactivity and produce harmful effects. This study aimed to investigate the role of a cardiac rehabilitation... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Complications of heart valve surgery lead to physical inactivity and produce harmful effects. This study aimed to investigate the role of a cardiac rehabilitation program and its long-term effect in patients after heart valve surgery.
METHODS
We performed a single-blind, randomized, controlled trial. Patients with heart valve surgery were randomly assigned to receive early cardiac rehabilitation (intervention group, 44 patients) or the usual care (control group, 43 patients). The intervention group performed sitting, standing, and walking exercises, followed by endurance training. The control group received usual care and did not engage in any physical activity. Physical function was assessed by the Short Physical Performance Battery (SPPB) and other measurement tools.
RESULTS
The intervention group showed a significant beneficial effect regarding physical capacity as shown by the SPPB and the 6-minute walking test at hospital discharge, and a better long-term effect was achieved at 6 months compared with the control group. An improvement in physical function (e.g., the SPPB) after hospital discharge predicted follow-up mortality (odds ratio = 0.416, 95% confidence interval: 0.218-0.792).
CONCLUSION
Early cardiac rehabilitation appears to be an effective approach to improve the physical function and survival of patients with heart valve surgery.
Topics: Cardiac Rehabilitation; Cardiac Surgical Procedures; Exercise Therapy; Heart Valves; Humans; Single-Blind Method
PubMed: 35899970
DOI: 10.1177/03000605211044320 -
Comprehensive Physiology Sep 2016Heart valves control unidirectional blood flow within the heart during the cardiac cycle. They have a remarkable ability to withstand the demanding mechanical... (Review)
Review
Heart valves control unidirectional blood flow within the heart during the cardiac cycle. They have a remarkable ability to withstand the demanding mechanical environment of the heart, achieving lifetime durability by processes involving the ongoing remodeling of the extracellular matrix. The focus of this review is on heart valve functional physiology, with insights into the link between disease-induced alterations in valve geometry, tissue stress, and the subsequent cell mechanobiological responses and tissue remodeling. We begin with an overview of the fundamentals of heart valve physiology and the characteristics and functions of valve interstitial cells (VICs). We then provide an overview of current experimental and computational approaches that connect VIC mechanobiological response to organ- and tissue-level deformations and improve our understanding of the underlying functional physiology of heart valves. We conclude with a summary of future trends and offer an outlook for the future of heart valve mechanobiology, specifically, multiscale modeling approaches, and the potential directions and possible challenges of research development. © 2016 American Physiological Society. Compr Physiol 6:1743-1780, 2016.
Topics: Animals; Biomechanical Phenomena; Heart Valve Diseases; Heart Valves; Humans
PubMed: 27783858
DOI: 10.1002/cphy.c150048 -
Frontiers in Immunology 2021Immune privilege is an evolutionary adaptation that protects vital tissues with limited regenerative capacity from collateral damage by the immune response. Classical... (Review)
Review
Immune privilege is an evolutionary adaptation that protects vital tissues with limited regenerative capacity from collateral damage by the immune response. Classical examples include the anterior chamber of the eye and the brain. More recently, the placenta, testes and articular cartilage were found to have similar immune privilege. What all of these tissues have in common is their vital function for evolutionary fitness and a limited regenerative capacity. Immune privilege is clinically relevant, because corneal transplantation and meniscal transplantation do not require immunosuppression. The heart valves also serve a vital function and have limited regenerative capacity after damage. Moreover, experimental and clinical evidence from heart valve transplantation suggests that the heart valves are spared from alloimmune injury. Here we review this evidence and propose the concept of heart valves as immune privileged sites. This concept has important clinical implications for heart valve transplantation.
Topics: Animals; Biological Evolution; Cell Proliferation; Heart Transplantation; Heart Valves; Humans; Immune Privilege; Regeneration
PubMed: 34447390
DOI: 10.3389/fimmu.2021.731361 -
Cardiovascular Research Feb 2021Heterogeneous macrophage lineages are present in the aortic and mitral valves of the heart during development and disease. These populations include resident macrophages... (Review)
Review
Heterogeneous macrophage lineages are present in the aortic and mitral valves of the heart during development and disease. These populations include resident macrophages of embryonic origins and recruited monocyte-derived macrophages prevalent in disease. Soon after birth, macrophages from haematopoietic lineages are recruited to the heart valves, and bone marrow transplantation studies in mice demonstrate that haematopoietic-derived macrophages continue to invest adult valves. During myxomatous heart valve disease, monocyte-derived macrophages are recruited to the heart valves and they contribute to valve degeneration in a mouse model of Marfan syndrome. Here, we review recent studies of macrophage lineages in heart valve development and disease with discussion of clinical significance and therapeutic applications.
Topics: Animals; Cardiovascular Agents; Cell Lineage; Gene Expression Regulation, Developmental; Heart Valve Diseases; Heart Valves; Humans; Macrophages; Molecular Targeted Therapy; Morphogenesis; Phenotype; Receptors, CCR2
PubMed: 32170926
DOI: 10.1093/cvr/cvaa062 -
The Journal of Thoracic and... Aug 2021
Review
2020 ACC/AHA guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
Topics: Consensus; Evidence-Based Medicine; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Heart Valves; Hemodynamics; Humans; Prosthesis Design; Recovery of Function; Risk Factors; Treatment Outcome
PubMed: 33972115
DOI: 10.1016/j.jtcvs.2021.04.002 -
Cardiovascular Engineering and... Jun 2018
Topics: Animals; Biomechanical Phenomena; Bioprosthesis; Cardiovascular Agents; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Heart Valves; Hemodynamics; Humans; Mechanotransduction, Cellular; Prosthesis Design; Regeneration; Tissue Engineering
PubMed: 29761407
DOI: 10.1007/s13239-018-0360-3 -
Biochimica Et Biophysica Acta Jul 2016Mechanical forces are instrumental to cardiovascular development and physiology. The heart beats approximately 2.6 billion times in a human lifetime and heart valves... (Review)
Review
Mechanical forces are instrumental to cardiovascular development and physiology. The heart beats approximately 2.6 billion times in a human lifetime and heart valves ensure that these contractions result in an efficient, unidirectional flow of the blood. Composed of endocardial cells (EdCs) and extracellular matrix (ECM), cardiac valves are among the most mechanically challenged structures of the body both during and after their development. Understanding how hemodynamic forces modulate cardiovascular function and morphogenesis is key to unraveling the relationship between normal and pathological cardiovascular development and physiology. Most valve diseases have their origins in embryogenesis, either as signs of abnormal developmental processes or the aberrant re-expression of fetal gene programs normally quiescent in adulthood. Here we review recent discoveries in the mechanobiology of cardiac valve development and introduce the latest technologies being developed in the zebrafish, including live cell imaging and optical technologies, as well as modeling approaches that are currently transforming this field. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.
Topics: Animals; Cell Differentiation; Cell Lineage; Cell Proliferation; Gene Expression Regulation, Developmental; Heart Valve Diseases; Heart Valves; Hemodynamics; Humans; Kruppel-Like Transcription Factors; Mechanotransduction, Cellular; Microscopy; Models, Animal; Morphogenesis; Stress, Mechanical; Zebrafish; Zebrafish Proteins
PubMed: 26608609
DOI: 10.1016/j.bbamcr.2015.11.014 -
Disease Models & Mechanisms Nov 2017The circulatory system consists of the heart, blood vessels and lymphatic vessels, which function in parallel to provide nutrients and remove waste from the body.... (Review)
Review
The circulatory system consists of the heart, blood vessels and lymphatic vessels, which function in parallel to provide nutrients and remove waste from the body. Vascular function depends on valves, which regulate unidirectional fluid flow against gravitational and pressure gradients. Severe valve disorders can cause mortality and some are associated with severe morbidity. Although cardiac valve defects can be treated by valve replacement surgery, no treatment is currently available for valve disorders of the veins and lymphatics. Thus, a better understanding of valves, their development and the progression of valve disease is warranted. In the past decade, molecules that are important for vascular function in humans have been identified, with mouse studies also providing new insights into valve formation and function. Intriguing similarities have recently emerged between the different types of valves concerning their molecular identity, architecture and development. Shear stress generated by fluid flow has also been shown to regulate endothelial cell identity in valves. Here, we review our current understanding of valve development with an emphasis on its mechanobiology and significance to human health, and highlight unanswered questions and translational opportunities.
Topics: Animals; Genetic Predisposition to Disease; Heart Valve Diseases; Heart Valves; Humans; Models, Biological; Stress, Mechanical
PubMed: 29125824
DOI: 10.1242/dmm.030825