Faculty Opinions recommendation of Functionally specialized junctions between endothelial cells of lymphatic vessels.

Author(s):  
William A Muller
Angiogenesis ◽  
2021 ◽  
Author(s):  
Corina Marziano ◽  
Gael Genet ◽  
Karen K. Hirschi

AbstractThere are two vascular networks in mammals that coordinately function as the main supply and drainage systems of the body. The blood vasculature carries oxygen, nutrients, circulating cells, and soluble factors to and from every tissue. The lymphatic vasculature maintains interstitial fluid homeostasis, transports hematopoietic cells for immune surveillance, and absorbs fat from the gastrointestinal tract. These vascular systems consist of highly organized networks of specialized vessels including arteries, veins, capillaries, and lymphatic vessels that exhibit different structures and cellular composition enabling distinct functions. All vessels are composed of an inner layer of endothelial cells that are in direct contact with the circulating fluid; therefore, they are the first responders to circulating factors. However, endothelial cells are not homogenous; rather, they are a heterogenous population of specialized cells perfectly designed for the physiological demands of the vessel they constitute. This review provides an overview of the current knowledge of the specification of arterial, venous, capillary, and lymphatic endothelial cell identities during vascular development. We also discuss how the dysregulation of these processes can lead to vascular malformations, and therapeutic approaches that have been developed for their treatment.


Author(s):  
Esak Lee ◽  
Niranjan B. Pandey ◽  
Aleksander S. Popel

Tumour and organ microenvironments are crucial for cancer progression and metastasis. Crosstalk between multiple non-malignant cell types in the microenvironments and cancer cells promotes tumour growth and metastasis. Blood and lymphatic endothelial cells (BEC and LEC) are two of the components in the microenvironments. Tumour blood vessels (BV), comprising BEC, serve as conduits for blood supply into the tumour, and are important for tumour growth as well as haematogenous tumour dissemination. Lymphatic vessels (LV), comprising LEC, which are relatively leaky compared with BV, are essential for lymphogenous tumour dissemination. In addition to describing the conventional roles of the BV and LV, we also discuss newly emerging roles of these endothelial cells: their crosstalk with cancer cells via molecules secreted by the BEC and LEC (also called angiocrine and lymphangiocrine factors). This review suggests that BEC and LEC in various microenvironments can be orchestrators of tumour progression and proposes new mechanism-based strategies to discover new therapies to supplement conventional anti-angiogenic and anti-lymphangiogenic therapies.


2009 ◽  
Vol 69 (6) ◽  
pp. 2669-2676 ◽  
Author(s):  
Francesca Spinella ◽  
Emirena Garrafa ◽  
Valeriana Di Castro ◽  
Laura Rosanò ◽  
Maria Rita Nicotra ◽  
...  

2017 ◽  
Vol 215 (1) ◽  
pp. 35-49 ◽  
Author(s):  
Tatiana V. Petrova ◽  
Gou Young Koh

Recent discoveries of novel functions and diverse origins of lymphatic vessels have drastically changed our view of lymphatic vasculature. Traditionally regarded as passive conduits for fluid and immune cells, lymphatic vessels now emerge as active, tissue-specific players in major physiological and pathophysiological processes. Lymphatic vessels show remarkable plasticity and heterogeneity, reflecting their functional specialization to control the tissue microenvironment. Moreover, alternative developmental origins of lymphatic endothelial cells in some organs may contribute to the diversity of their functions in adult tissues. This review aims to summarize the most recent findings of organotypic differentiation of lymphatic endothelial cells in terms of their distinct (patho)physiological functions in skin, lymph nodes, small intestine, brain, and eye. We discuss recent advances in our understanding of the heterogeneity of lymphatic vessels with respect to the organ-specific functional and molecular specialization of lymphatic endothelium, such as the hybrid blood-lymphatic identity of Schlemm’s canal, functions of intestinal lymphatics in dietary fat uptake, and discovery of meningeal lymphatic vasculature and perivascular brain lymphatic endothelial cells.


2012 ◽  
Vol 23 (6) ◽  
pp. 707-710 ◽  
Author(s):  
Ana Carolina de Mesquita Netto ◽  
Mariana Batista de Oliveira ◽  
Vanessa Fátima Bernardes ◽  
Carolina Cavaliéri Gomes ◽  
Ricardo Santiago Gomez

Lymphangiomas are benign hamartomatous lesions of lymphatic vessels. Wilms Tumor 1 (WT1) is a transcription factor that is activated in some human neoplasias. WT1 protein expression is observed in endothelial cells during angiogenesis and is a useful marker to distinguish between vascular proliferations and vascular malformations. The purpose of the present study is to report a case series of oral lymphangiomas together with an immunohistochemical investigation of WT1. Seventeen cases of oral lymphangioma were retrieved and reviewed. Immunohistochemical analysis of WT1 protein was performed and pyogenic granuloma samples were used as positive controls. The male/female ratio was 1.125 and most of the lesions occurred in young subjects. While pyogenic granuloma showed positive staining for WT1, the endothelial cells lining the thin-walled dilated lymphatic vessels of lymphangiomas were negative for this protein. The findings strengthen the idea that oral lymphangioma is a vascular malformation characterized by lymphatic dilatation without significant endothelial proliferation.


1996 ◽  
Vol 176 (1) ◽  
pp. 76-85 ◽  
Author(s):  
Jörg Wilting ◽  
Ralf Birkenhäger ◽  
Anne Eichmann ◽  
Haymo Kurz ◽  
Georg Martiny-Baron ◽  
...  

2002 ◽  
Vol 82 (3) ◽  
pp. 673-700 ◽  
Author(s):  
Lotta Jussila ◽  
Kari Alitalo

Blood and lymphatic vessels develop in a parallel, but independent manner, and together form the circulatory system allowing the passage of fluid and delivering molecules within the body. Although the lymphatic vessels were discovered already 300 years ago, at the same time as the blood circulation was described, the lymphatic system has remained relatively neglected until recently. This is in part due to the difficulties in recognizing these vessels in tissues because of a lack of specific markers. Over the past few years, several molecules expressed specifically in the lymphatic endothelial cells have been characterized, and knowledge about the lymphatic system has started to accumulate again. The vascular endothelial growth factor (VEGF) family of growth factors and receptors is involved in the development and growth of the vascular endothelial system. Two of its family members, VEGF-C and VEGF-D, regulate the lymphatic endothelial cells via their receptor VEGFR-3. With the aid of these molecules, lymphatic endothelial cells can be isolated and cultured, allowing detailed studies of the molecular properties of these cells. Also the role of the lymphatic endothelium in immune responses and certain pathological conditions can be studied in more detail, as the blood and lymphatic vessels seem to be involved in many diseases in a coordinated manner. Discoveries made so far will be helpful in the diagnosis of certain vascular tumors, in the design of specific treatments for lymphedema, and in the prevention of metastatic tumor spread via the lymphatic system.


2012 ◽  
Vol 302 (1) ◽  
pp. H215-H223 ◽  
Author(s):  
Zhi-Xin Yan ◽  
Zhao-Hua Jiang ◽  
Ning-Fei Liu

Angiopoietin (Ang)-2, a ligand of the receptor tyrosine kinase Tie2, is known to be involved in the regulation of embryonic lymphangiogenesis. However, the role of Ang-2 in postnatal pathological lymphangiogenesis, such as inflammation, is largely unknown. We used a combination of imaging, molecular, and cellular approaches to investigate whether Ang-2 is involved in inflammatory lymphangiogenesis. We observed strong and continuous expression of Ang-2 on newly generated lymphatic vessels for 2 wk in sutured corneas of BALB/c mice. This expression was concurrent with an increased number of lymphatic vessels. TNF-α expression also increased, with peak TNF-α expression occurring before peak Ang-2 expression was reached. In vitro experiments showed that TNF-α stimulates Ang-2 and Tie2 and ICAM-1 expression on human lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BECs). Ang-2 alone did not affect the biological behavior of LECs, whereas Ang-2 combined with TNF-α significantly promoted the proliferation of LECs but not BECs. In mouse models, blockade of Ang-2 with L1-10, an Ang-2-specific inhibitor, significantly inhibited lymphangiogenesis but promoted angiogenesis. These results clearly indicate that Ang-2 acts as a crucial regulator of inflammatory lymphangiogenesis by sensitizing the lymphatic vasculature to inflammatory stimuli, thereby directly promoting lymphangiogenesis. The involvement of Ang-2 in inflammatory lymphangiogenesis provides a strong rationale for the exploitation of anti-Ang-2 treatment in the prevention and treatment of tumor metastasis and transplant rejection.


Author(s):  
Noriki Fujimoto ◽  
Yuliang He ◽  
Marco D’Addio ◽  
Carlotta Tacconi ◽  
Michael Detmar ◽  
...  

ABSTRACTLymph nodes (LNs) are highly organized secondary lymphoid organs that mediate adaptive immune responses to antigens delivered via afferent lymphatic vessels. Lymphatic endothelial cells (LECs) line intranodal lymphatic sinuses and organize lymph and antigen distribution. LECs also directly regulate T cells, mediating peripheral tolerance to self-antigens, and play a major role in many diseases including cancer metastasis. However, little is known about the phenotypic and functional heterogeneity of LN LECs. Using single-cell RNA sequencing, we comprehensively defined the transcriptome of LECs in murine skin-draining LNs, and identified new markers and functions of distinct LEC subpopulations. We found that LECs residing in the subcapsular sinus have an unanticipated function in scavenging of modified LDL and also identified a specific cortical LEC subtype implicated in rapid lymphocyte egress from LNs. Our data provide new insights into the diversity of LECs in murine lymph nodes and a rich resource for future studies into the regulation of immune responses by lymph node LECs.


2020 ◽  
Vol 2 (1) ◽  
pp. R93-R104 ◽  
Author(s):  
Karthik Amudhala Hemanthakumar ◽  
Riikka Kivelä

Endothelial cells (ECs) line the inner surface of all blood and lymphatic vessels throughout the body, making endothelium one of the largest tissues. In addition to its transport function, endothelium is now appreciated as a dynamic organ actively participating in angiogenesis, permeability and vascular tone regulation, as well as in the development and regeneration of tissues. The identification of endothelial-derived secreted factors, angiocrines, has revealed non-angiogenic mechanisms of endothelial cells in both physiological and pathological tissue remodeling. In the heart, ECs play a variety of important roles during cardiac development as well as in growth, homeostasis and regeneration of the adult heart. To date, several angiocrines affecting cardiomyocyte growth in response to physiological or pathological stimuli have been identified. In this review, we discuss the effects of angiogenesis and EC-mediated signaling in the regulation of cardiac hypertrophy. Identification of the molecular and metabolic signals from ECs during physiological and pathological cardiac growth could provide novel therapeutic targets to treat heart failure, as endothelium is emerging as one of the potential target organs in cardiovascular and metabolic diseases.


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