Emerging Approaches to Understanding Microvascular Endothelial Heterogeneity: A Roadmap for Developing Anti-Inflammatory Therapeutics
The endothelium is the inner layer of all blood vessels and it regulates hemostasis. It also plays an active role in the regulation of the systemic inflammatory response. Systemic inflammatory disease often results in alterations in vascular endothelium barrier function, increased permeability, exce...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/15/7770 |
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| author | Qingliang Yang Harshani Wijerathne Jordan C. Langston Mohammad F. Kiani Laurie E. Kilpatrick |
| author_facet | Qingliang Yang Harshani Wijerathne Jordan C. Langston Mohammad F. Kiani Laurie E. Kilpatrick |
| author_sort | Qingliang Yang |
| collection | DOAJ |
| description | The endothelium is the inner layer of all blood vessels and it regulates hemostasis. It also plays an active role in the regulation of the systemic inflammatory response. Systemic inflammatory disease often results in alterations in vascular endothelium barrier function, increased permeability, excessive leukocyte trafficking, and reactive oxygen species production, leading to organ damage. Therapeutics targeting endothelium inflammation are urgently needed, but strong concerns regarding the level of phenotypic heterogeneity of microvascular endothelial cells between different organs and species have been expressed. Microvascular endothelial cell heterogeneity in different organs and organ-specific variations in endothelial cell structure and function are regulated by intrinsic signals that are differentially expressed across organs and species; a result of this is that neutrophil recruitment to discrete organs may be regulated differently. In this review, we will discuss the morphological and functional variations in differently originated microvascular endothelia and discuss how these variances affect systemic function in response to inflammation. We will review emerging in vivo and in vitro models and techniques, including microphysiological devices, proteomics, and RNA sequencing used to study the cellular and molecular heterogeneity of endothelia from different organs. A better understanding of microvascular endothelial cell heterogeneity will provide a roadmap for developing novel therapeutics to target the endothelium. |
| first_indexed | 2024-03-10T09:16:17Z |
| format | Article |
| id | doaj.art-c34f57b236214d4ba7a530a9d97e4d56 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:16:17Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c34f57b236214d4ba7a530a9d97e4d562023-11-22T05:38:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012215777010.3390/ijms22157770Emerging Approaches to Understanding Microvascular Endothelial Heterogeneity: A Roadmap for Developing Anti-Inflammatory TherapeuticsQingliang Yang0Harshani Wijerathne1Jordan C. Langston2Mohammad F. Kiani3Laurie E. Kilpatrick4Department of Mechanical Engineering, Temple University, Philadelphia, PA 19122, USADepartment of Chemistry, University of Kansas, Lawrence, KS 66045, USADepartment of Bioengineering, Temple University, Philadelphia, PA 19122, USADepartment of Mechanical Engineering, Temple University, Philadelphia, PA 19122, USACenter for Inflammation, Clinical and Translational Lung Research, Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USAThe endothelium is the inner layer of all blood vessels and it regulates hemostasis. It also plays an active role in the regulation of the systemic inflammatory response. Systemic inflammatory disease often results in alterations in vascular endothelium barrier function, increased permeability, excessive leukocyte trafficking, and reactive oxygen species production, leading to organ damage. Therapeutics targeting endothelium inflammation are urgently needed, but strong concerns regarding the level of phenotypic heterogeneity of microvascular endothelial cells between different organs and species have been expressed. Microvascular endothelial cell heterogeneity in different organs and organ-specific variations in endothelial cell structure and function are regulated by intrinsic signals that are differentially expressed across organs and species; a result of this is that neutrophil recruitment to discrete organs may be regulated differently. In this review, we will discuss the morphological and functional variations in differently originated microvascular endothelia and discuss how these variances affect systemic function in response to inflammation. We will review emerging in vivo and in vitro models and techniques, including microphysiological devices, proteomics, and RNA sequencing used to study the cellular and molecular heterogeneity of endothelia from different organs. A better understanding of microvascular endothelial cell heterogeneity will provide a roadmap for developing novel therapeutics to target the endothelium.https://www.mdpi.com/1422-0067/22/15/7770microvascular endothelial cellsheterogeneityinflammationendothelial barrier permeabilityleukocytestransmigration |
| spellingShingle | Qingliang Yang Harshani Wijerathne Jordan C. Langston Mohammad F. Kiani Laurie E. Kilpatrick Emerging Approaches to Understanding Microvascular Endothelial Heterogeneity: A Roadmap for Developing Anti-Inflammatory Therapeutics International Journal of Molecular Sciences microvascular endothelial cells heterogeneity inflammation endothelial barrier permeability leukocytes transmigration |
| title | Emerging Approaches to Understanding Microvascular Endothelial Heterogeneity: A Roadmap for Developing Anti-Inflammatory Therapeutics |
| title_full | Emerging Approaches to Understanding Microvascular Endothelial Heterogeneity: A Roadmap for Developing Anti-Inflammatory Therapeutics |
| title_fullStr | Emerging Approaches to Understanding Microvascular Endothelial Heterogeneity: A Roadmap for Developing Anti-Inflammatory Therapeutics |
| title_full_unstemmed | Emerging Approaches to Understanding Microvascular Endothelial Heterogeneity: A Roadmap for Developing Anti-Inflammatory Therapeutics |
| title_short | Emerging Approaches to Understanding Microvascular Endothelial Heterogeneity: A Roadmap for Developing Anti-Inflammatory Therapeutics |
| title_sort | emerging approaches to understanding microvascular endothelial heterogeneity a roadmap for developing anti inflammatory therapeutics |
| topic | microvascular endothelial cells heterogeneity inflammation endothelial barrier permeability leukocytes transmigration |
| url | https://www.mdpi.com/1422-0067/22/15/7770 |
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