scholarly journals Late developing cardiac lymphatic vasculature supports adult zebrafish heart function and regeneration

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Michael RM Harrison ◽  
Xidi Feng ◽  
Guqin Mo ◽  
Antonio Aguayo ◽  
Jessi Villafuerte ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Lymphatic System ◽  
Vascular System ◽  
Heart Function ◽  
Lymphatic Vessels ◽  
Adult Zebrafish ◽  
Heart Patients ◽  
Scar Size ◽  
Lymphatic Vasculature ◽  
Zebrafish Heart

The cardiac lymphatic vascular system and its potentially critical functions in heart patients have been largely underappreciated, in part due to a lack of experimentally accessible systems. We here demonstrate that cardiac lymphatic vessels develop in young adult zebrafish, using coronary arteries to guide their expansion down the ventricle. Mechanistically, we show that in cxcr4a mutants with defective coronary artery development, cardiac lymphatic vessels fail to expand onto the ventricle. In regenerating adult zebrafish hearts the lymphatic vasculature undergoes extensive lymphangiogenesis in response to a cryoinjury. A significant defect in reducing the scar size after cryoinjury is observed in zebrafish with impaired Vegfc/Vegfr3 signaling that fail to develop intact cardiac lymphatic vessels. These results suggest that the cardiac lymphatic system can influence the regenerative potential of the myocardium.

scholarly journals Author response: Late developing cardiac lymphatic vasculature supports adult zebrafish heart function and regeneration

2019 ◽  
Author(s):  
Michael RM Harrison ◽  
Xidi Feng ◽  
Guqin Mo ◽  
Antonio Aguayo ◽  
Jessi Villafuerte ◽  
...  
Keyword(s):  
Heart Function ◽  
Author Response ◽  
Adult Zebrafish ◽  
Lymphatic Vasculature ◽  
Zebrafish Heart

Lymphangiogenesis in development and disease

2007 ◽  
Vol 98 (08) ◽  
pp. 304-310 ◽  
Author(s):  
Ruediger Liersch ◽  
Michael Detmar
Keyword(s):  
Lymph Nodes ◽  
Cancer Metastasis ◽  
Lymphatic System ◽  
Vascular System ◽  
Malignant Tumors ◽  
Inflammatory Diseases ◽  
Transplant Rejection ◽  
Lymphatic Vessels ◽  
Lipid Uptake ◽  
Molecular Control

SummaryThe lymphatic vascular system plays an important role in the maintenance of fluid homeostasis, in the afferent immune response, in the intestinal lipid uptake and in the metastatic spread of malignant cells. The recent discovery of specific markers and growth factors for lymphatic endothelium and the establishment of genetic mouse models with impairment of lymphatic function have provided novel insights into the molecular control of the lymphatic system in physiology and in embryonic development. They have also identified molecular pathways whose mutational inactivation leads to human diseases associated with lymphedema. Moreover, the lymphatic system plays a major role in chronic inflammatory diseases and in transplant rejection. Importantly, malignant tumors can directly promote lymphangiogenesis within the primary tumor and in draining lymph nodes, leading to enhanced cancer metastasis to lymph nodes and beyond. Based upon these findings, novel therapeutic strategies are currently being developed that aim at inhibiting or promoting the formation and function of lymphatic vessels in disease.

scholarly journals Lymphatic vascular morphogenesis in development, physiology, and disease

2011 ◽  
Vol 193 (4) ◽  
pp. 607-618 ◽  
Author(s):  
Stefan Schulte-Merker ◽  
Amélie Sabine ◽  
Tatiana V. Petrova
Keyword(s):  
Dietary Fat ◽  
Interstitial Fluid ◽  
Vascular System ◽  
Lymphatic Vessels ◽  
Genetically Engineered ◽  
Novel Therapies ◽  
Vascular Morphogenesis ◽  
Pathological Conditions ◽  
Lymphatic Vasculature ◽  
Cell Dissemination

The lymphatic vasculature constitutes a highly specialized part of the vascular system that is essential for the maintenance of interstitial fluid balance, uptake of dietary fat, and immune response. Recently, there has been an increased awareness of the importance of lymphatic vessels in many common pathological conditions, such as tumor cell dissemination and chronic inflammation. Studies of embryonic development and genetically engineered animal models coupled with the discovery of mutations underlying human lymphedema syndromes have contributed to our understanding of mechanisms regulating normal and pathological lymphatic morphogenesis. It is now crucial to use this knowledge for the development of novel therapies for human diseases.

scholarly journals Lymphatic Senescence: Current Updates and Perspectives

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 293
Author(s):  
Sebastian Lucio Filelfi ◽  
Alberto Onorato ◽  
Bianca Brix ◽  
Nandu Goswami
Keyword(s):  
Lymphatic System ◽  
Light Exposure ◽  
Contractile Activity ◽  
Lymphatic Vessels ◽  
Nerve Fibers ◽  
Treatment Modalities ◽  
Lymphatic Flow ◽  
Lymphatic Vasculature ◽  
And Function ◽  
The Impact

Lymphatic flow is necessary for maintenance of vital physiological functions in humans and animals. To carry out optimal lymphatic flow, adequate contractile activity of the lymphatic collectors is necessary. Like in all body systems, aging has also an effect on the lymphatic system. However, limited knowledge is available on how aging directly affects the lymphatic system anatomy, physiology and function. We investigated how senescence leads to alterations in morphology and function of the lymphatic vessels. We used the strategy of a review to summarize the scientific literature of studies that have been published in the area of lymphatic senescence. Searches were carried out on PubMed and Web of Science using predefined search queries. We obtained an initial set of 1060 publications. They were filtered to 114 publications based on strict inclusion and exclusion criteria. Finally, the most appropriate 57 studies that specifically addressed lymphatic senescence have been selected for the preparation of this review. Analysis of the literature showed that lymphatic senescence is associated with alterations in lymphatic muscles and nerve fibers, lymphatic glycocalyx function of lymphatic endothelial cells, effects of chronic ultraviolet light exposure and oxidative stress as well as changes in lymphatic pump, acute inflammation responses and immune function. The current review underscores the relevance of the understudied area of lymphatic senescence. Continued research on the impact of aging on the structure and function of the lymphatic vasculature is needed to provide further insights to develop innovative clinical diagnostic—and treatment—modalities as well as to reduce the morbidity associated with diseases related to the lymphatic system.

scholarly journals The Lymphatic System in Zebrafish Heart Development, Regeneration and Disease Modeling

2021 ◽  
Vol 8 (2) ◽  
pp. 21
Author(s):  
Xidi Feng ◽  
Stanislao Travisano ◽  
Caroline A. Pearson ◽  
Ching-Ling Lien ◽  
Michael R. M. Harrison
Keyword(s):  
Heart Development ◽  
Lymphatic System ◽  
Disease Modeling ◽  
Developed Countries ◽  
Heart Tissue ◽  
Therapeutic Interventions ◽  
Lymphatic Vasculature ◽  
Lymphatic Development ◽  
Zebrafish Heart ◽  
Novel Therapeutic

Heart disease remains the single largest cause of death in developed countries, and novel therapeutic interventions are desperately needed to alleviate this growing burden. The cardiac lymphatic system is the long-overlooked counterpart of the coronary blood vasculature, but its important roles in homeostasis and disease are becoming increasingly apparent. Recently, the cardiac lymphatic vasculature in zebrafish has been described and its role in supporting the potent regenerative response of zebrafish heart tissue investigated. In this review, we discuss these findings in the wider context of lymphatic development, evolution and the promise of this system to open new therapeutic avenues to treat myocardial infarction and other cardiopathologies.

Lymphatic Vasculature: An Emerging Therapeutic Target and Drug Delivery Route

2021 ◽  
Vol 72 (1) ◽  
pp. 167-182
Author(s):  
Wenjing Xu ◽  
Natalie R. Harris ◽  
Kathleen M. Caron
Keyword(s):  
Drug Delivery ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Therapeutic Benefit ◽  
Model Systems ◽  
Clinical Settings ◽  
Innovative Drug ◽  
Critical System ◽  
Organ Specific ◽  
Lymphatic Vasculature

The lymphatic system has received increasing scientific and clinical attention because a wide variety of diseases are linked to lymphatic pathologies and because the lymphatic system serves as an ideal conduit for drug delivery. Lymphatic vessels exert heterogeneous roles in different organs and vascular beds, and consequently, their dysfunction leads to distinct organ-specific outcomes. Although studies in animal model systems have led to the identification of crucial lymphatic genes with potential therapeutic benefit, effective lymphatic-targeted therapeutics are currently lacking for human lymphatic pathological conditions. Here, we focus on the therapeutic roles of lymphatic vessels in diseases and summarize the promising therapeutic targets for modulating lymphangiogenesis or lymphatic function in preclinical or clinical settings. We also discuss considerations for drug delivery or targeting of lymphatic vessels for treatment of lymphatic-related diseases. The lymphatic vasculature is rapidly emerging as a critical system for targeted modulation of its function and as a vehicle for innovative drug delivery.

scholarly journals A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules

2015 ◽  
Vol 212 (7) ◽  
pp. 991-999 ◽  
Author(s):  
Aleksanteri Aspelund ◽  
Salli Antila ◽  
Steven T. Proulx ◽  
Tine Veronica Karlsen ◽  
Sinem Karaman ◽  
...  
Keyword(s):  
Subarachnoid Space ◽  
Interstitial Fluid ◽  
Vascular System ◽  
Lymphatic Vessels ◽  
Cervical Lymph Nodes ◽  
Brain Interstitial Fluid ◽  
Lymphatic Vasculature ◽  
The Central Nervous System ◽  
Base Of The Skull ◽  
The Brain

The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease.

scholarly journals Structure and physiology of the lymphatic vasculature

2020 ◽  
Vol 19 (3) ◽  
pp. 5-18
Author(s):  
G. I. Lobov ◽  
Zh. V. Nepiyushchikh
Keyword(s):  
Endothelial Cells ◽  
Lymph Nodes ◽  
Immune Cells ◽  
Vascular System ◽  
Lymphatic Vessels ◽  
Extracellular Fluid ◽  
Past Century ◽  
Physiological Control ◽  
Comprehensive Overview ◽  
Lymphatic Vasculature

The lymphatic vascular system is a highly organized network of structurally and functionally connected specialized lymphatic vessels of various sizes and lymph nodes that perform metabolic and transport functions. Lymph is a blood plasma filtrate that comprises antigen-presenting cells and lymphocytes. Via lymph, excess fluid and extravasated proteins are removed from the tissues. The lymphatic system supports an extracellular fluid homeostasis that is favorable for optimal tissue functioning by removing substances that result from metabolism or cell death, as well as optimizing immunity against bacteria, viruses and other antigens. Although the lymphatic vasculature is not formally considered part of the immune system, it is crucial for the traffic of antigens and immune cells. In addition, lymphatic endothelial cells can supply antigens and express factors that modulate immune responses. After an inflammatory stimulus, endothelial cells produce chemokines, which recruit immune cells to the lymph nodes. Unlike the circulatory system with a centralized pump, the movement of lymph through the network of lymphatic vessels is provided by forces that stimulate the initial formation of lymph in the tissues and the ability of the lymphatic vessels and nodes to rhythmically contract, providing increased pressure and lymph movement in the proximal direction. Since the metabolic rate in various organs and tissues varies significantly depending on the functional state of the tissue, the blood flow through the tissue and the amount of lymph formed also change significantly. The lymphatic vasculature has several circuits for regulating lymph flow. This review provides a comprehensive overview of the important results obtained over the past century and discusses the molecular and physiological control of the transport function of lymphatic vessels and nodes.

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