scholarly journals Endothelial Dysfunction: From a Pathophysiological Mechanism to a Potential Therapeutic Target

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 78
Author(s):  
Pasquale Ambrosino ◽  
Guido Grassi ◽  
Mauro Maniscalco
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Therapeutic Target ◽  
Lymphatic Vessels ◽  
The Body ◽  
Pathophysiological Mechanism ◽  
Potential Therapeutic Target ◽  
Interior Surface

The endothelium is considered the largest organ of the body, composed of a monolayer of endothelial cells (ECs) lining the interior surface of blood and lymphatic vessels [...]

scholarly journals Vascular endothelial cell specification in health and disease

Angiogenesis ◽  
2021 ◽  
Author(s):  
Corina Marziano ◽  
Gael Genet ◽  
Karen K. Hirschi
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Current Knowledge ◽  
Vascular Malformations ◽  
Immune Surveillance ◽  
Vascular Endothelial Cell ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cell ◽  
The Body ◽  
Vascular Networks

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.

Vascular Growth Factors and Lymphangiogenesis

2002 ◽  
Vol 82 (3) ◽  
pp. 673-700 ◽  
Author(s):  
Lotta Jussila ◽  
Kari Alitalo
Keyword(s):  
Endothelial Cells ◽  
Growth Factors ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
The Body ◽  
Vascular Tumors ◽  
Vascular Endothelial ◽  
Lymphatic Endothelial Cells ◽  
Independent Manner ◽  
Tumor Spread

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.

scholarly journals Angiogenesis and angiocrines regulating heart growth

2020 ◽  
Vol 2 (1) ◽  
pp. R93-R104 ◽  
Author(s):  
Karthik Amudhala Hemanthakumar ◽  
Riikka Kivelä
Keyword(s):  
Endothelial Cells ◽  
Vascular Tone ◽  
Metabolic Diseases ◽  
Cardiac Development ◽  
Lymphatic Vessels ◽  
The Body ◽  
Transport Function ◽  
Secreted Factors ◽  
Target Organs ◽  
Treat Heart Failure

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.

scholarly journals Lymphatic system and adipose tissue: Crosstalk in health and disease

2021 ◽  
Vol 18 (3) ◽  
pp. 336-344
Author(s):  
V. V. Klimontov ◽  
D. M. Bulumbaeva
Keyword(s):  
Endothelial Cells ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Inflammatory Cells ◽  
The Body ◽  
Push Button ◽  
Secondary Lymphedema

The lymphatic system (LS) is one of the main integrative systems of the body, providing protective and transport functions. In recent years, interactions between LS and adipose tissue (AT) have been of particular interest. Lymphatic vessels play an important role in metabolic and regulatory functions of AT, acting as a collector of lipolysis products and adipokines. In its turn, hormones and adipocytokines that produced in adipocytes (including leptin, adiponectin, IL-6, TNF-α, etc.) affect the function of lymphatic endothelial cells and control the growth of lymphatic vessels. Cooperation between LS and AT becomes pathogenetically and clinically important in lymphedema and obesity. It is known that both primary and secondary lymphedema are characterized by increased fat accumulation which is associated with the severity of lymphostasis and inflammation. Similarly, in obesity, the drainage function of LS is impaired, which is accompanied by perilymphatic mononuclear infiltration in the AT. The development of these changes is facilitated by endocrine dysfunction of adipocytes and impaired production of adipocytokines. The increase in the production of inflammatory mediators and the disruption of the traffic of inflammatory cells causes a further deterioration in the outflow of interstitial fluid and exacerbates the inflammation of the AT, thereby forming a vicious circle. The role of lymphangiogenesis in AT remodeling in obesity needs further research. Another promising area of research is the study of the role of intestinal LS in the development of obesity and related disorders. It has been shown that the transport of chylomicrons from the intestine depends on the expression of a number of molecular mediators (VEGF-C, DLL-4, neuropilin-1, VEGFR-1, CD36/FAT, etc.)in the endotheliocytes of the intestinal lymphatic vessels, as well as the functioning of «push-button» and “zippering” junctions between endothelial cells. New approach to the treatment of obesity based on blockade of lymphatic chylomicrontransport has been experimentally substantiated. Further identification of the molecular mechanisms and signaling pathways that determine the remodeling of AT in lymphedema and obesity are likely to provide new approaches to the treatment of these diseases.

scholarly journals Lymphovenous hemostasis and the role of platelets in regulating lymphatic flow and lymphatic vessel maturation

Blood ◽  
2016 ◽  
Vol 128 (9) ◽  
pp. 1169-1173 ◽  
Author(s):  
John D. Welsh ◽  
Mark L. Kahn ◽  
Daniel T. Sweet
Keyword(s):  
Endothelial Cells ◽  
Lymphatic Vessel ◽  
Vascular System ◽  
Lymphatic Vessels ◽  
Lymph Flow ◽  
The Body ◽  
Lymphatic Endothelial Cells ◽  
Lymphatic Circulation ◽  
Vessel Maturation

Abstract Aside from the established role for platelets in regulating hemostasis and thrombosis, recent research has revealed a discrete role for platelets in the separation of the blood and lymphatic vascular systems. Platelets are activated by interaction with lymphatic endothelial cells at the lymphovenous junction, the site in the body where the lymphatic system drains into the blood vascular system, resulting in a platelet plug that, with the lymphovenous valve, prevents blood from entering the lymphatic circulation. This process, known as “lymphovenous hemostasis,” is mediated by activation of platelet CLEC-2 receptors by the transmembrane ligand podoplanin expressed by lymphatic endothelial cells. Lymphovenous hemostasis is required for normal lymph flow, and mice deficient in lymphovenous hemostasis exhibit lymphedema and sometimes chylothorax phenotypes indicative of lymphatic insufficiency. Unexpectedly, the loss of lymph flow in these mice causes defects in maturation of collecting lymphatic vessels and lymphatic valve formation, uncovering an important role for fluid flow in driving endothelial cell signaling during development of collecting lymphatics. This article summarizes the current understanding of lymphovenous hemostasis and its effect on lymphatic vessel maturation and synthesizes the outstanding questions in the field, with relationship to human disease.

scholarly journals The role of the lymphatic system in the homeostasis of the interstitial fluid in the lung and pleural liquid

2019 ◽  
Vol 18 (1) ◽  
pp. 104-112 ◽  
Author(s):  
G. I. Lobov
Keyword(s):  
Endothelial Cells ◽  
Respiratory System ◽  
Interstitial Fluid ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Current Data ◽  
The Body ◽  
Almost All ◽  
Preclinical And Clinical Studies

Accomplishments in the identifcation of lymphatic endothelial cells and the ability to differentiate them from the endothelial cells of blood vessels have contributed to progress in recent decades in studying the role of the lymphatic system in the body. Preclinical and clinical studies of the last decade have shown that changes in the lymphatic vascular network are observed in almost all lung diseases. At the same time, it remains unclear whether the lymphatic vessels and lung nodes are being part of the overall process of lung remodeling or they make a defnite contribution to the pathogenesis of diseases of the respiratory system. This review presents current data on the morphology and physiology of lymphatic vessels and nodes, their role in the regulation of interstitial fluid homeostasis, lipid transportation and immune responses as well as describes the mechanisms of regulation of the transport function of lymphatic vessels. Data on the role of the lymphatic system of the lungs in the exchange of fluid in the interstitial space of the lungs are presented in the review. The results of studies of the last two decades on the formation and reabsorption of pleural fluid and the role of various lymphatic networks in regulating its volume are described. Finally, modern ideas on the mechanisms of pulmonary edema are outlined and important questions of the lymphatic biology of the respiratory system are identifed, still remaining unanswered today.

Wake-up call for endothelial cells

Blood ◽  
2010 ◽  
Vol 115 (12) ◽  
pp. 2336-2337 ◽  
Author(s):  
Yihai Cao
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Therapeutic Target ◽  
Potential Therapeutic Target

VEGF exhibits broad vascular functions by activation of its VEGFRs in endothelial cells. In this issue of Blood, Suehiro and colleagues show that VEGF-induced endothelial activities are mediated by activation of Egr-3 transcription factor and that Egr-3 is a potential therapeutic target for angiogenesis-related diseases.

scholarly journals Stromal cell-derived factor-1 as a potential therapeutic target for osteoarthritis and rheumatoid arthritis

2019 ◽  
Vol 10 ◽  
pp. 204062231988253 ◽  
Author(s):  
Robert Bragg ◽  
William Gilbert ◽  
Ahmed M. Elmansi ◽  
Carlos M. Isales ◽  
Mark W. Hamrick ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Target ◽  
Animal Studies ◽  
Stromal Cell ◽  
Degenerative Joint Disease ◽  
The Body ◽  
Joint Disease ◽  
Endochondral Bone Formation ◽  
Potential Therapeutic Target ◽  
Stromal Cell Derived Factor

With age, joints become subject to chronic inflammatory processes that lead to degeneration of articular cartilage. Although multifactorial, cytokines have been shown to play a role in the pathogenesis of these chronic disease states. Stromal cell-derived factor 1 (SDF-1) is a chemokine that has been shown to be active in homeostatic mechanisms and developmental processes throughout the body, such as endochondral bone formation. SDF-1 plays a role in the transition from cartilage to bone. Although it has been shown to be a factor in normal development, it has also been shown to involve in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA). In RA, SDF-1 has been shown to stimulate the recruitment of proinflammatory cells, as well as osteoclasts to the synovium, aiding in the facilitation of synovial degradation. Similarly, in OA, SDF-1 has been shown to regulate key proteins involved in the degradation of the cartilage of the joint. Because of its role in degenerative joint disease, SDF-1 has been investigated as a potential therapeutic target. Animal studies have been employing SDF-1 inhibitors, such as AMD3100 and T140, to study their effects on attenuating degenerative joint disease. These studies have shown promising results in slowing the progression of cartilage degradation and could potentially be used as therapeutic target for humans OA and RA.

scholarly journals Experimental faecal peritonitis alters response to 5-hydroxytryptamine in mesenteric lymphatic vessels

2020 ◽  
Vol 5 (3) ◽  
pp. 35-41
Author(s):  
A. A. Egorova ◽  
E. A. Avramenko
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Blood Vessels ◽  
Intraperitoneal Injection ◽  
Lymphatic Vessels ◽  
Faecal Peritonitis ◽  
Contraction Amplitude ◽  
Contraction Frequency ◽  
Endothelial Denudation ◽  
Pressure Myograph

Aim. To compare the reactions to 5-hydroxytryptamine (5-HT, serotonin) in the mesenteric lymphangions upon endothelial denudation and during experimental faecal peritonitis as compared with the control lymphangions. Materials and Methods. Experiments were performed on the intestinal lymph trunk lymphangions of rats using a pressure myograph system. We examined the changes in contraction frequency and amplitude as well as tonic reactions upon the addition of 5-HT (10-8-10-4 M). Experimental peritonitis was caused by an intraperitoneal injection of feces. Results. Faecal peritonitis reduced contraction frequency and amplitude in mesenteric lymphangions. 5-HT increased contraction amplitude only at low concentration (10-8 M) and did not alter the tonic reactions. Upon endothelial denudation, serotonin inhibited contraction frequency and amplitude in the lymphangions. As 5-HT stimulates motility through 5-НТ2 receptors and α2-adrenoceptors on endothelial cells, faecal peritonitis abates the sensitivity of such receptors to 5-HT. Conclusion. In experimental faecal peritonitis, alterations in lymphatic vessels are reminiscent of those in blood vessels. Endothelial dysfunction disturbs the response of lymphatic vessels to 5-HT.

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