Endothelial Cells

The great wall of the circulatory system

What if I told you that the blood vessel walls are made of cells that aren’t just bystanders, but actively participate in various functions? Endothelial cells form a wall in the inner lining of the blood vessels along with other cells, giving rise to an endocrine organ known as the endothelium [1]. Found all over the body, these cells are intricately involved in functions such as blood flow regulation, vascular permeability, barrier function, and inflammation. Since they are involved with the cardiovascular system and the immune system, their dysfunction can lead to debilitating diseases [2].

Many faces of endothelial cells

The endothelium was first described by the Swiss‐born embryologist Wilhelm His in 1865. Wilhelm His observed that cells derived from the mesoderm lined the inner cavities of the body, such as blood vessels and lymphatics. He named these cells ‘epithelia’ [3]. They are found throughout the human body, forming a single layer of approximately 1–6 × 1013 cells that occupy a surface area of 1–7 m2 [4].

Advances in electron microscopy techniques in the 1950s revealed that endothelial cells are anatomically heterogeneous; subsequently, single-cell RNA sequencing has demonstrated this heterogeneity to be tissue-specific [5]. Endothelial cells are commonly flat, but can also be plump or cuboidal in shape, giving them a characteristic cobblestone-like appearance. Their thickness can range from 0.1 μm in capillaries to 1 μm in the aorta [1, 6].

What makes endothelial cells so remarkable is their diversity in shape and function varies depending on the tissue type. For example, endothelial cells in the central nervous system form the blood-brain barrier, which protects the brain from harmful substances such as pathogens and toxins [7]. Additionally, endothelial cells play an important function in pregnancy through the expression of estrogen receptors, which facilitates pregnancy-related changes in the uterine artery endothelial cells [8].

Endothelial cells in immune response and inflammation

Endothelial cells not only act as a barrier against harmful invaders such as pathogens, but also play an active role in the immune system through several mechanisms. They serve as a means of transportation for mobile immune cells, release paracrine factors such as chemokines, interleukins and interferons, and mobilize immune cells to the site of inflammation using adhesion molecules [2]. They participate in innate immune response through the activation of toll-like receptors on endothelial cells which can detect pathogen-associated molecular patterns [9, 10]. However, there is tissue-specific variability in the expression of toll-like receptors. In fact, inflammation can induce the expression of toll-like receptors [11]. Additionally, endothelial cells can also mount an inflammatory response to tissue damage since they express receptors that can detect damage-associated molecular pattern molecules released by stressed or injured cells [2]. Therefore, endothelial cells must navigate a tough balancing act between promoting inflammation and facilitating the movement of immune cells to sites of inflammation.

Endothelial cells in diseases

Dysfunction in endothelial cells can lead to the pathogenesis of various vascular diseases since they are intricately involved in so many functions throughout the body. For example, improper mediation of vascular permeability can lead to the development of atheroma, which is a chronic inflammation where a lesion forms on the endothelial wall. This lesion might prevent blood flow to the organ fed by the artery, possibly causing an infarct or stroke. Consequently, treatment options include the application of an antibody for vascular endothelial growth factor A, which may inhibit the growth of an atheroma [12].

Additionally, many therapies that treat vascular and inflammatory dysfunction also target endothelial cells. This includes statins which target adhesion molecules to treat atherosclerosis, non-steroidal anti-inflammatory agents which lower blood flow to reduce inflammation, and anti-histamines which lower vascular permeability to treat allergic rhinitis to name a few [13].

Recognizing and appreciating the labs working in this space

• Friedrich Jung, Institute of Biotechnology, Molecular Cell Biology, Brandenburg University of Technology, Senftenberg, Germany. https://www.b-tu.de/en/molecular-cell-biology/team/group-members
• Caterina Sturtzel, Innovative Cancer Models, St. Anna Children’s Cancer Research Institute, Vienna, Austria. https://www.zandr-ccri.at/team/caterina-sturtzel-phd/
• Kristy Red-Horse, Institute for Stem Cell Biology and Regenerative Medicine, Department of Biology, Stanford University, California, USA. https://redhorselab.com/research
• William C Aird, Division of Molecular and Vascular Medicine, Department of Medicine, and Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Massachusetts, USA. https://www.linkedin.com/in/william-aird/
• Luisa Iruela-Arispe, Department of Cell & Developmental Biology, Northwestern University Feinberg School of Medicine, Illinois, USA. https://labs.feinberg.northwestern.edu/arispe/ , X: @NUFeinbergMed
• Mayra B. Pastore, Department of Obstetrics/Gynecology, Perinatal Research Laboratories, University of Wisconsin-Madison, Wisconsin, USA. https://ingrahamlab.ucsf.edu/content/mayra-b-pastore-phd
• Stanislav Kotlyarov, Department of Nursing, Ryazan State Medical University, Ryazan, Russia. https://www.researchgate.net/profile/Stanislav-Kotlyarov , X: @DrKotlyarov
• Judith Hellman, Department of Anesthesia and Perioperative Care, University of California, California, USA. https://bms.ucsf.edu/people/judith-hellman-md
• Jordan Pober, Pathology and Dermatology, Yale University School of Medicine, Connecticut, USA. https://medicine.yale.edu/profile/jordan-pober/
• William Sessa, Pharmacology, Yale University School of Medicine, Connecticut, USA. https://medicine.yale.edu/lab/sessa/

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References

1. Krüger-Genge, A. et al. “Vascular Endothelial Cell Biology: An Update.” Int J Mol Sci, vol. 20, no. 18, 2019, doi:10.3390/ijms20184411.
2. Sturtzel, C. “Endothelial Cells.” Adv Exp Med Biol, vol. 1003, 2017, pp. 71–91, doi:10.1007/978–3–319–57613–8_4.
3. Richardson, M. K. and G. Keuck. “The Revolutionary Developmental Biology of Wilhelm His, Sr.” Biol Rev Camb Philos Soc, vol. 97, no. 3, 2022, pp. 1131–60, doi:10.1111/brv.12834.
4. Favero, G. et al. “Endothelium and Its Alterations in Cardiovascular Diseases: Life Style Intervention.” Biomed Res Int, vol. 2014, 2014, p. 801896, doi:10.1155/2014/801896.
5. Paik, D. T. et al. “Single-Cell Rna Sequencing Unveils Unique Transcriptomic Signatures of Organ-Specific Endothelial Cells.” Circulation, vol. 142, no. 19, 2020, pp. 1848–62, doi:10.1161/circulationaha.119.041433.
6. Aird, W. C. “Phenotypic Heterogeneity of the Endothelium: I. Structure, Function, and Mechanisms.” Circ Res, vol. 100, no. 2, 2007, pp. 158–73, doi:10.1161/01.RES.0000255691.76142.4a.
7. Domigan, C. K. and M. L. Iruela-Arispe. “Recent Advances in Vascular Development.” Curr Opin Hematol, vol. 19, no. 3, 2012, pp. 176–83, doi:10.1097/MOH.0b013e3283523e90.
8. Pastore, M. B. et al. “Estrogen Receptor-Α and Estrogen Receptor-Β in the Uterine Vascular Endothelium during Pregnancy: Functional Implications for Regulating Uterine Blood Flow.” Semin Reprod Med, vol. 30, no. 1, 2012, pp. 46–61, doi:10.1055/s-0031–1299597.
9. Kotlyarov, S. “Immune Function of Endothelial Cells: Evolutionary Aspects, Molecular Biology and Role in Atherogenesis.” Int J Mol Sci, vol. 23, no. 17, 2022, doi:10.3390/ijms23179770.
10. Khakpour, S. et al. “Vascular Endothelial Cell Toll-Like Receptor Pathways in Sepsis.” Innate Immun, vol. 21, no. 8, 2015, pp. 827–46, doi:10.1177/1753425915606525.
11. Fitzner, N. et al. “Human Skin Endothelial Cells Can Express All 10 Tlr Genes and Respond to Respective Ligands.” Clin Vaccine Immunol, vol. 15, no. 1, 2008, pp. 138–46, doi:10.1128/cvi.00257–07.
12. Hansson, G. K. and P. Libby. “The Immune Response in Atherosclerosis: A Double-Edged Sword.” Nat Rev Immunol, vol. 6, no. 7, 2006, pp. 508–19, doi:10.1038/nri1882.
13. Pober, J. S. and W. C. Sessa. “Evolving Functions of Endothelial Cells in Inflammation.” Nat Rev Immunol, vol. 7, no. 10, 2007, pp. 803–15, doi:10.1038/nri2171.

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About the author:

DR. NOWRIN AHMED

Content Editor The League of Extraordinary Cell Types, Sci-Illustrate Stories

Dr. Nowrin Ahmed has a PhD in Behavioral and Neural Sciences from Rutgers University-Newark (NJ, USA) where she studied the interactions between the midline thalamus and the amygdala. She also studied amygdala circuits during her post-doctoral fellowship at Rutgers University — Newark. Currently, she works as a freelance medical writer. Dr. Nowrin enjoys sharing the beauty of science with diverse audiences.

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Nelli Aghekyan, did a bachelor’s and master’s in Architecture in Armenia, after studying architecture and interior design for 6 years, she concentrated on her drawing skills and continued her path in the illustration world. She works mainly on children’s book illustrations, some of her books are now being published. Currently living in Italy, she works as a full-time freelance artist, collaborating with different companies and clients.

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DR. EMANUELE PETRETTO

Animator The League of Extraordinary Cell Types, Sci-Illustrate Stories

Dr. Petretto received his Ph.D. in Biochemistry at the University of Fribourg, Switzerland, focusing on the behavior of matter at nanoscopic scales and the stability of colloidal systems. Using molecular dynamics simulations, he explored the delicate interaction among particles, interfaces, and solvents.

Currently, he is fully pursuing another delicate interaction: the intricate interplay between art and science. Through data visualization, motion design, and games, he wants to show the wonders of the complexity surrounding us.

About the series:

The League of Extraordinary Cell types

The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types in our body, that make our hearts tick ❤.

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