scholarly journals New insights about the lymphatic vasculature in cardiovascular diseases

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1811 ◽  
Author(s):  
Xiaolei Liu ◽  
Guillermo Oliver

The heart contains a complex network of blood and lymphatic vessels. The coronary blood vessels provide the cardiac tissue with oxygen and nutrients and have been the major focus of research for the past few decades. Cardiac lymphatic vessels, which consist of lymphatic capillaries and collecting lymphatic vessels covering all layers of the heart, transport excess fluid from the interstitium and play important roles in maintaining tissue fluid balance. Unlike for the coronary blood vessels, until a few years ago, not much information was available on the origin and function of the cardiac-associated lymphatic vasculature. A growing body of evidence indicates that cardiac lymphatic vessels (lymphatics) may serve as a therapeutic cardiovascular target.

2020 ◽  
Vol 6 (50) ◽  
pp. eabc2697
Author(s):  
Kim Pin Yeo ◽  
Hwee Ying Lim ◽  
Chung Hwee Thiam ◽  
Syaza Hazwany Azhar ◽  
Caris Tan ◽  
...  

A functional lymphatic vasculature is essential for tissue fluid homeostasis, immunity, and lipid clearance. Although atherosclerosis has been linked to adventitial lymphangiogenesis, the functionality of aortic lymphatic vessels draining the diseased aorta has never been assessed and the role of lymphatic drainage in atherogenesis is not well understood. We develop a method to measure aortic lymphatic transport of macromolecules and show that it is impaired during atherosclerosis progression, whereas it is ameliorated during lesion regression induced by ezetimibe. Disruption of aortic lymph flow by lymphatic ligation promotes adventitial inflammation and development of atherosclerotic plaque in hypercholesterolemic mice and inhibits ezetimibe-induced atherosclerosis regression. Thus, progression of atherosclerotic plaques may result not only from increased entry of atherogenic factors into the arterial wall but also from reduced lymphatic clearance of these factors as a result of aortic lymph stasis. Our findings suggest that promoting lymphatic drainage might be effective for treating atherosclerosis.


Blood ◽  
2012 ◽  
Vol 120 (11) ◽  
pp. 2340-2348 ◽  
Author(s):  
Ying Yang ◽  
José Manuel García-Verdugo ◽  
Mario Soriano-Navarro ◽  
R. Sathish Srinivasan ◽  
Joshua P. Scallan ◽  
...  

Abstract The lymphatic vasculature preserves tissue fluid balance by absorbing fluid and macromolecules and transporting them to the blood vessels for circulation. The stepwise process leading to the formation of the mammalian lymphatic vasculature starts by the expression of the gene Prox1 in a subpopulation of blood endothelial cells (BECs) on the cardinal vein (CV) at approximately E9.5. These Prox1-expressing lymphatic endothelial cells (LECs) will exit the CV to form lymph sacs, primitive structures from which the entire lymphatic network is derived. Until now, no conclusive information was available regarding the cellular processes by which these LEC progenitors exit the CV without compromising the vein's integrity. We determined that LECs leave the CV by an active budding mechanism. During this process, LEC progenitors are interconnected by VE-cadherin–expressing junctions. Surprisingly, we also found that Prox1-expressing LEC progenitors were present not only in the CV but also in the intersomitic vessels (ISVs). Furthermore, as LEC progenitors bud from the CV and ISVs into the surrounding mesenchyme, they begin expressing the lymphatic marker podoplanin, migrate away from the CV, and form the lymph sacs. Analyzing this process in Prox1-null embryos revealed that Prox1 activity is necessary for LEC progenitors to exit the CV.


Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 293
Author(s):  
Sebastian Lucio Filelfi ◽  
Alberto Onorato ◽  
Bianca Brix ◽  
Nandu Goswami

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.


2021 ◽  
Vol 50 (1) ◽  
pp. 13
Author(s):  
Tatsuo Tomita

<p><strong>Objective</strong>. In the current study, we compared the distribution of blood and lymphatic vessels from paraffin-embedded tissues with those of frozen tissues of normal human and rhesus monkey.</p><p><strong> Materials and Methods</strong>. We performed immunocytochemical staining for lymphatic and blood vessels using LYVE-1 for lymphatic vessels and von Willebrand factor (F-8) for blood ves- sels.</p><p><strong>Results</strong>. Normal tissues included spleen, lymph node, liver, pancreas, salivary gland, colon, diaphragm, heart, lung, thyroid, adrenal gland, kidney, ovary, endometrium, and prostate. Splenic sinusoids were stained for LYVE-1 and F-8 in the frozen sections, supporting that the sinusoid is a lymphoreticular system and blood vessel in structure and function. In frozen sections, the lymphatic sinusoids were consistently positive for LYVE-1, while hepatic sinusoids were positive for LYVE-1, but not for F-8. Thus, lymphatic and blood vessels were more readily detected in frozen tissue sections than in the paraffin-embedded sections. In the endometrium, lymphatic vessels were not diffusely immunostained in paraffin-embedded sections. However, frozen sections detected cyclic changes of lymphatic vessels, growing from basalis to functionalis in the menstrual cycle. Lymphatic vessels were immunostained in many organs using frozen sections. Small pulmonary blood vessels were not immunostained by F-8 in the periphery of the bronchial vessel tree most likely these smallest blood vessels were not immunostained due to less F-8 attached to their endothelia. Conclusion. The present findings illustrate the differences in the immunostaining of blood vessels in sections obtained from paraffin-embedded tissues and those from frozen tissue. These new findings may be relevant for the basic histology and histopathology of lymphatic and blood vessels.</p>


Author(s):  
Saleh Yazdani ◽  
Gerjan Navis ◽  
Jan-Luuk Hillebrands ◽  
Harry van Goor ◽  
Jacob van den Born

Lymphatic vessels (LVs) are involved in a number of physiological and pathophysiological processes such as fluid homoeostasis, immune surveillance, and resolution of inflammation and wound healing. Lymphangiogenesis, the outgrowth of existing LVs and the formation of new ones, has received increasing attention over the past decade on account of its prominence in organ physiology and pathology, which has been enabled by the development of specific tools to study lymph vessel functions. Several studies have been devoted to renal lymphatic vasculature and lymphangiogenesis in kidney diseases, such as chronic renal transplant dysfunction, primary renal fibrotic disorders, proteinuria, diabetic nephropathy and renal inflammation. This review describes the most recent findings on lymphangiogenesis, with a specific focus on renal lymphangiogenesis and its impact on renal diseases. We suggest renal lymphatics as a possible target for therapeutic interventions in renal medicine to dampen tubulointerstitial tissue remodelling and improve renal functioning.


2004 ◽  
Vol 287 (5) ◽  
pp. H2115-H2121 ◽  
Author(s):  
E. K. Walsh ◽  
H. Huang ◽  
Z. Wang ◽  
J. Williams ◽  
R. de Crom ◽  
...  

Our objective was to investigate the potential role of selective endothelial nitric oxide (NO) synthase (eNOS) overexpression in coronary blood vessels in the control of myocardial oxygen consumption (MVo2). Transgenic (Tg) eNOS-overexpressing mice (eNOS Tg) ( n = 22) and wild-type (WT) mice ( n = 24) were studied. Western blot analysis indicated greater than sixfold increase of eNOS in cardiac tissue. Echocardiography in awake mice indicated no difference in cardiac function between WT and eNOS Tg; however, systolic pressure in eNOS Tg mice decreased significantly (126 ± 2.3 to 109 ± 2.3 mmHg; P < 0.05), whereas heart rate (HR) was not different. Total peripheral resistance (TPR) was also decreased (9.8 ± 0.8 to 7.6 ± 0.4 4 mmHg·ml−1·min; P < 0.05) in eNOS Tg. Furthermore, female eNOS Tg mice showed even lower TPR (7.2 ± 0.4 mmHg·ml−1·min) compared with male eNOS mice (8.6 ± 0.5, mmHg·ml·min−1; P < 0.05). Left ventricular slices were isolated from WT and eNOS Tg mice. With the use of a Clark-type oxygen electrode in an airtight bath, MVo2 was determined as the percent decrease during increasing doses (10−10 to 10−4 mol/l) of bradykinin (BK), carbachol (CCh), forskolin (10−12 to 10−6 mol/l), or S-nitroso- N-acetyl penicillamine (SNAP; 10−7 to 10−4 mol/l). Baseline MVo2 was not different between WT (181 ± 13 nmol·g−1·min−1) and eNOS Tg (188 ± 14 nmol·g−1·min−1). BK decreased MVo2 (10−4 mol/l) in WT by 17% ± 1.1 and 33% ± 2.7 in eNOS Tg ( P < 0.05). CCh also decreased MVo2, 10−4 mol/l, in WT by 20% ± 1.7 and 31% ± 2.0 in eNOS Tg ( P < 0.05). Forskolin (10−6 mol/l) or SNAP (10−4 mol/l) also decreased MVo2 in WT by 24% ± 2.8 and 36% ± 1.8 versus eNOS 31% ± 1.8 and 37% ± 3.5, respectively. N-nitro-l-arginine methyl ester (10−3 mol/l) inhibited the MVo2 reduction to BK, CCh, and forskolin by a similar degree ( P < 0.05), but not to SNAP. Thus selective overexpression of eNOS in cardiac blood vessels in mice enhances the control of MVo2 by eNOS-derived NO.


Blood ◽  
2011 ◽  
Vol 117 (16) ◽  
pp. 4387-4393 ◽  
Author(s):  
Annika Ålgars ◽  
Marika Karikoski ◽  
Gennady G. Yegutkin ◽  
Patrizia Stoitzner ◽  
Jussi Niemelä ◽  
...  

Abstract CD73 is involved in the extracellular ATP metabolism by dephosphorylating extracellular AMP to adenosine and thus regulating permeability of the blood vessels and leukocyte traffic into the tissues. It is also present on lymphatic vessels where its distribution and function have not been characterized. We found that CD73 is expressed on a subpopulation of afferent lymph vessels but is absent on efferent lymphatics, unlike LYVE-1 and podoplanin, which are expressed on both types of lymphatics. The extracellular nucleotide metabolism on lymphatic endothelium differs from that on blood vessel endothelium as lymphatic endothelium has lower NTPDase and higher ecto-5′-nucleotidase/CD73 activity than blood vascular endothelium. In knockout mice, the lack of CD73 on lymphocytes decreases migration of lymphocytes to the draining lymph nodes more than 50% while CD73-deficient lymph vessels mediate lymphocyte trafficking as efficiently as the wild-type lymphatics. Thus, although endothelial CD73 is important for permeability and leukocyte extravasation in blood vessels, it does not have a role in these functions on lymphatics. Instead, lymphocyte CD73 is intimately involved in lymphocyte migration via afferent lymphatic vessels.


2021 ◽  
Author(s):  
Zsuzsanna Fabry ◽  
Martin Hsu ◽  
Collin Laaker ◽  
Andy Madrid ◽  
Melinda Herbath ◽  
...  

Abstract Meningeal lymphatic vessels residing in the dural layer above the sinuses of the brain, meninges at the base of the brain, and near the cribriform plate have all been shown to drain fluid, cells, and antigens. We have previously reported that meningeal lymphatics near the cribriform plate undergo VEGFR3-dependent lymphangiogenesis during experimental autoimmune encephalomyelitis (EAE) to facilitate excess drainage. Using single-cell RNA sequencing (scRNA-seq), we report that neuroinflammation changes the phenotype and function of cribriform plate lymphatic endothelial cells (cpLECs). Upregulation of genes involved in antigen presentation, adhesion to leukocytes, and immunoregulatory molecules were verified by flow cytometry and functional assays. The inflamed cpLECs retain dendritic cells and to lesser extent CD4 T cells, creating an immune-regulatory niche that represents a previously underappreciated interface in the regulation of neuroinflammation. Additionally, the discontinuity of the arachnoid membrane near cpLECs provides unrestricted access to the cerebrospinal fluid (CSF) for immune surveillance. These findings may lead to new therapeutic approaches to neuroinflammatory diseases.


2020 ◽  
Vol 16 (6) ◽  
pp. 899-907
Author(s):  
O. Yu. Isaykina ◽  
V. B. Rozanov ◽  
А. А. Aleksandrov ◽  
M. B. Kotova

Aim. To study the association of smoking with indicators of the structure and function of blood vessels in a sample of middle-aged men.Material and methods. This study is part of a 32-year prospective cohort observation of males starting in childhood (11-12 years). The study included 301 (30.0%) representatives of the original population sample aged 41-44 years. The examination included a survey on a standard questionnaire with an assessment of the status and intensity of smoking, of anthropometric indicators, blood pressure (BP), and determination of the blood lipid spectrum. The stiffness of the arterial wall and central pressure were measured by the method of applanation tonometry. The carotid intima-media thickness of the common carotid artery (C-IMT) was estimated by the method of ultrasonic duplex scanning of the main vessels of the neck.Results. Of the 301 men examined, aged 41-44 years, 92 (30.6%) people never smoked, 73 (24.3%) smoked in the past and 136 (45.2%) people currently smoke. Former smokers were divided by the intensity of smoking in the past as follows: less than 20 cigarettes/day were smoked by 41 (56.0%) people, and ≥20 cigarettes/day - 32 (44.0%) people. Among current smokers, less than 20 cigarettes/day were smoked by 63 (46.0%) people, and ≥20 cigarettes - 73 (54.0%) people. Current smokers have a statistically significantly higher level of triglycerides and lower cholesterol of high density lipoproteins in the blood, augmentation index (AIx), augmentation blood pressure and C-IMT thicker than non-smokers. The thickness of the C-IMT and AIx was statistically significantly greater among current smokers who smoked 20 or more cigarettes daily. Men who smoked in the past had significantly greater body weight, waist circumference and pulse wave velocity. 12.4% of AIx variability was attributable to current smoking combined with variability in alcohol consumption, blood glucose, and heart rate. The body mass index (BMI) and ethanol consumption are independent determinants of peripheral and central systolic pressure, and account for 17.8% and 18.6% of their variance, respectively. The combined contribution of current smoking, age, BMI, low-density lipoprotein cholesterol and plasma glucose to the thickness variability of C-IMT was 13.7%. Among men with a smoking duration in the past >10 years, the levels of total cholesterol, triglycerides and arterial stiffness indicators - AIx, pulse pressure amplification were higher compared to peers with a shorter smoking duration.Conclusion. Current smoking is associated with atherogenic changes in the blood lipid spectrum, impaired structure and function of the main arteries. Moreover, the severity of structural and functional disorders of the arteries is associated with the intensity of current smoking. If you give up smoking, there is a potential possibility of reversibility of these vascular disorders.


Author(s):  
K.E. Krizan ◽  
J.E. Laffoon ◽  
M.J. Buckley

With increase use of tissue-integrated prostheses in recent years it is a goal to understand what is happening at the interface between haversion bone and bulk metal. This study uses electron microscopy (EM) techniques to establish parameters for osseointegration (structure and function between bone and nonload-carrying implants) in an animal model. In the past the interface has been evaluated extensively with light microscopy methods. Today researchers are using the EM for ultrastructural studies of the bone tissue and implant responses to an in vivo environment. Under general anesthesia nine adult mongrel dogs received three Brånemark (Nobelpharma) 3.75 × 7 mm titanium implants surgical placed in their left zygomatic arch. After a one year healing period the animals were injected with a routine bone marker (oxytetracycline), euthanized and perfused via aortic cannulation with 3% glutaraldehyde in 0.1M cacodylate buffer pH 7.2. Implants were retrieved en bloc, harvest radiographs made (Fig. 1), and routinely embedded in plastic. Tissue and implants were cut into 300 micron thick wafers, longitudinally to the implant with an Isomet saw and diamond wafering blade [Beuhler] until the center of the implant was reached.


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