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Lymphatic Vascular Growth and Remodeling in Pathophysiology-New Findings and Avenues

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (10 March 2023) | Viewed by 3570

Special Issue Editors


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Guest Editor
Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Interests: lymphangiogenesis; inflammatory regulation; immune responses; fibrosis; secondary lymphedema; T cells; lymphatic trafficking
Special Issues, Collections and Topics in MDPI journals
Meinig School of Biomedical Engineering, College of Engineering, Cornell University, Ithaca, NY 14853, USA
Interests: biomedical engineering; organs-on-chips; immunity; lymphatics; cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The lymphatic system consists of a network of unidirectional vasculature, with single-layered, permeable initial lymphatics leading to multilayered, larger collecting vessels. Fluid and immune cells are absorbed from these initial lymphatics, propelled by collectors, and sent to immunological filters, known as lymph nodes, where antigens are trapped, immune responses are generated, and clear fluid further mixes with systemic circulation. Thus, the lymphatic system plays a major role in fluid and immune homeostasis. Even though lymphatic vessels were identified several centuries ago, only with the last 2–3 decades has lymphatic research started to grow.

Before the surge in lymphatic research, in earlier years, lymphatic research identified and characterized lymphatic growth factors, and signaling cascades during development and adulthood. Within the last decade or so, more research was also performed to understand the role of lymphatics in lymphedema, cancer, and obesity pathologies. Together, these findings showed that the lymphatic system not only actively drains fluids, immune cells, and lipids but also plays a major role in multiple pathophysiological conditions involving different organ systems such as the heart, the brain, the kidneys, the lungs, the liver, and skin, to mention a few. An impaired lymphatic function has been implicated in several pathologies such as cancer, lymphedema, cardiovascular diseases, hypertension, atherosclerosis, inflammation, obesity, inflammatory bowel disease, asthma, emphysema, chronic obesity, glaucoma, Alzheimer’s disease, and several others. With every year, new aspects related to the lymphatic system are revealed by research but is accompanied by an equal number of intriguing new questions. This wealth of knowledge and the pursuit of answers to these new questions will immensely help develop therapeutic interventions to alter lymphatic function that can pave the way to curing the above mentioned myriad of diseases.

This Special Issue aims to summarize our current progress and to provide a better understanding of the molecular and pathological aspects of lymphatics in different organ systems. This issue also invites cutting-edge research findings that shed light on several unanswered questions that were raised in lymphatic research during the recent decade.

Dr. Raghu P. Kataru
Dr. Esak Lee
Guest Editors

Manuscript Submission Information

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Keywords

  • lymphatic vessel growth
  • lymphatic vessels in development and physiology
  • tumor lymphatic vessels
  • lymphatic vessels in obesity and metabolic disorders
  • secondary lymphedema
  • lymphatic dysfunction
  • lymphatic regression and apoptosis

Published Papers (2 papers)

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Research

11 pages, 3179 KiB  
Article
Molecular Profiling of Lymphatic Endothelial Cell Activation In Vitro
by Marta Turati, Gianluca Mattei, Alessia Boaretto, Alberto Magi, Maura Calvani and Roberto Ronca
Int. J. Mol. Sci. 2023, 24(23), 16587; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242316587 - 22 Nov 2023
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Abstract
The lymphatic vascular system plays a key role in cancer progression. Indeed, the activation of lymphatic endothelial cells (LECs) through the lymphangiogenic process allows for the formation of new lymphatic vessels (LVs) that represent the major route for the dissemination of solid tumors. [...] Read more.
The lymphatic vascular system plays a key role in cancer progression. Indeed, the activation of lymphatic endothelial cells (LECs) through the lymphangiogenic process allows for the formation of new lymphatic vessels (LVs) that represent the major route for the dissemination of solid tumors. This process is governed by a plethora of cancer-derived and microevironmental mediators that strictly activate and control specific molecular pathways in LECs. In this work we used an in vitro model of LEC activation to trigger lymphangiogenesis using a mix of recombinant pro-lymphangiogenic factors (VFS) and a co-culture system with human melanoma cells. Both systems efficiently activated LECs, and under these experimental conditions, RNA sequencing was exploited to unveil the transcriptional profile of activated LECs. Our data demonstrate that both recombinant and tumor cell-mediated activation trigger significant molecular pathways associated with endothelial activation, morphogenesis, and cytokine-mediated signaling. In addition, this system provides information on new genes to be further investigated in the lymphangiogenesis process and open the possibility for further exploitation in other tumor contexts where lymphatic dissemination plays a relevant role. Full article
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18 pages, 2704 KiB  
Article
E-Cigarette Aerosol Condensate Leads to Impaired Coronary Endothelial Cell Health and Restricted Angiogenesis
by Michael Chhor, Esra Tulpar, Tara Nguyen, Charles G. Cranfield, Catherine A. Gorrie, Yik Lung Chan, Hui Chen, Brian G. Oliver, Lana McClements and Kristine C. McGrath
Int. J. Mol. Sci. 2023, 24(7), 6378; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24076378 - 28 Mar 2023
Cited by 1 | Viewed by 1905
Abstract
Cardiovascular disease (CVD) is a leading cause of mortality worldwide, with cigarette smoking being a major preventable risk factor. Smoking cessation can be difficult due to the addictive nature of nicotine and the withdrawal symptoms following cessation. Electronic cigarettes (e-Cigs) have emerged as [...] Read more.
Cardiovascular disease (CVD) is a leading cause of mortality worldwide, with cigarette smoking being a major preventable risk factor. Smoking cessation can be difficult due to the addictive nature of nicotine and the withdrawal symptoms following cessation. Electronic cigarettes (e-Cigs) have emerged as an alternative smoking cessation device, which has been increasingly used by non-smokers; however, the cardiovascular effects surrounding the use of e-Cigs remains unclear. This study aimed to investigate the effects of e-Cig aerosol condensate (EAC) (0 mg and 18 mg nicotine) in vitro on human coronary artery endothelial cells (HCAEC) and in vivo on the cardiovascular system using a mouse model of ‘e-vaping’. In vitro results show a decrease in cell viability of HCAEC when exposed to EAC either directly or after exposure to conditioned lung cell media (p < 0.05 vs. control). Reactive oxygen species were increased in HCAEC when exposed to EAC directly or after exposure to conditioned lung cell media (p < 0.0001 vs. control). ICAM-1 protein expression levels were increased after exposure to conditioned lung cell media (18 mg vs. control, p < 0.01). Ex vivo results show an increase in the mRNA levels of anti-angiogenic marker, FKBPL (p < 0.05 vs. sham), and endothelial cell adhesion molecule involved in barrier function, ICAM-1 (p < 0.05 vs. sham) in murine hearts following exposure to electronic cigarette aerosol treatment containing a higher amount of nicotine. Immunohistochemistry also revealed an upregulation of FKBPL and ICAM-1 protein expression levels. This study showed that despite e-Cigs being widely used for tobacco smoking cessation, these can negatively impact endothelial cell health with a potential to lead to the development of cardiovascular disease. Full article
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