scholarly journals Angiogenesis and angiocrines regulating heart growth

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.

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.


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.


2021 ◽  
Vol 18 (3) ◽  
pp. 336-344
Author(s):  
V. V. Klimontov ◽  
D. M. Bulumbaeva

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.


Blood ◽  
2016 ◽  
Vol 128 (9) ◽  
pp. 1169-1173 ◽  
Author(s):  
John D. Welsh ◽  
Mark L. Kahn ◽  
Daniel T. Sweet

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.


Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 78
Author(s):  
Pasquale Ambrosino ◽  
Guido Grassi ◽  
Mauro Maniscalco

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 [...]


2019 ◽  
Vol 18 (1) ◽  
pp. 104-112 ◽  
Author(s):  
G. I. Lobov

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.


2020 ◽  
Vol 20 (8) ◽  
pp. 1262-1267
Author(s):  
Haojun Yang ◽  
Hanyang Liu ◽  
YuWen Jiao ◽  
Jun Qian

Background: G protein-coupled bile acid receptor (TGR5) is involved in a number of metabolic diseases. The aim of this study was to identify the role of TGR5 after Roux-en-Y gastric bypass (GBP). Methods: Wild type and TGR5 knockout mice (tgr5-/-) were fed a high-fat diet (HFD) to establish the obesity model. GBP was performed. The changes in body weight and food intake were measured. The levels of TGR5 and peptide YY (PYY) were evaluated by RT-PCR, Western blot, and ELISA. Moreover, the L-cells were separated from wild type and tgr5-/- mice. The levels of PYY in L-cells were evaluated by ELISA. Results: The body weights were significantly decreased after GBP in wild type mice (p<0.05), but not tgr5-/- mice (p>0.05). Food intake was reduced after GBP in wild type mice, but also not significantly affected in tgr5-/- mice (p>0.05). The levels of PYY were significantly increased after GBP compared with the sham group (p<0.05); however, in tgr5-/- mice the expression of PYY was not significantly affected (p>0.05). After INT-777 stimulation in L-cells obtained from murine intestines, the levels of PYY were significantly increased in L-cells tgr5+/+ (p<0.05). Conclusion: Our study suggests that GBP up-regulated the expression of TGR5 in murine intestines, and increased the levels of PYY, which further reduced food intake and decreased the body weight.


2021 ◽  
Vol 8 (7) ◽  
pp. 117
Author(s):  
Giovanni Cilia ◽  
Laura Zavatta ◽  
Rosa Ranalli ◽  
Antonio Nanetti ◽  
Laura Bortolotti

The deformed wing virus (DWV) is one of the most common honey bee pathogens. The virus may also be detected in other insect species, including Bombus terrestris adults from wild and managed colonies. In this study, individuals of all stages, castes, and sexes were sampled from three commercial colonies exhibiting the presence of deformed workers and analysed for the presence of DWV. Adults (deformed individuals, gynes, workers, males) had their head exscinded from the rest of the body and the two parts were analysed separately by RT-PCR. Juvenile stages (pupae, larvae, and eggs) were analysed undissected. All individuals tested positive for replicative DWV, but deformed adults showed a higher number of copies compared to asymptomatic individuals. Moreover, they showed viral infection in their heads. Sequence analysis indicated that the obtained DWV amplicons belonged to a strain isolated in the United Kingdom. Further studies are needed to characterize the specific DWV target organs in the bumblebees. The result of this study indicates the evidence of DWV infection in B. terrestris specimens that could cause wing deformities, suggesting a relationship between the deformities and the virus localization in the head. Further studies are needed to define if a specific organ could be a target in symptomatic bumblebees.


Author(s):  
Minsoo Kang ◽  
Sun Kyoung Han ◽  
Suhyun Kim ◽  
Sungyeon Park ◽  
Yerin Jo ◽  
...  

Abstract Hepatic gluconeogenesis is the central pathway for glucose generation in the body. The imbalance between glucose synthesis and uptake leads to metabolic diseases such as obesity, diabetes, and cardiovascular diseases. Small leucine zipper protein (sLZIP) is an isoform of LZIP and it mainly functions as a transcription factor. Although sLZIP is known to regulate the transcription of genes involved in various cellular processes, the role of sLZIP in hepatic glucose metabolism is not known. In this study, we investigated the regulatory role of sLZIP in hepatic gluconeogenesis and its involvement in metabolic disorder. We found that sLZIP expression was elevated during glucose starvation, leading to the promotion of phosphoenolpyruvate carboxylase and glucose-6-phosphatase expression in hepatocytes. However, sLZIP knockdown suppressed the expression of the gluconeogenic enzymes under low glucose conditions. sLZIP also enhanced glucose production in the human liver cells and mouse primary hepatic cells. Fasting-induced cyclic adenosine monophosphate impeded sLZIP degradation. Results of glucose and pyruvate tolerance tests showed that sLZIP transgenic mice exhibited abnormal blood glucose metabolism. These findings suggest that sLZIP is a novel regulator of gluconeogenic enzyme expression and plays a role in blood glucose homeostasis during starvation.


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