Evolutionary Protection of Krüppel-Like Factors 2 and 4 in the Development of the Mature Hemovascular System
A properly functioning hemovascular system, consisting of circulating innate immune cells and endothelial cells (ECs), is essential in the distribution of nutrients to distant tissues while ensuring protection from invading pathogens. Professional phagocytes (e.g., macrophages) and ECs have co-evolv...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.645719/full |
| _version_ | 1818607494002376704 |
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| author | David R. Sweet David R. Sweet David R. Sweet Cherry Lam Mukesh K. Jain Mukesh K. Jain |
| author_facet | David R. Sweet David R. Sweet David R. Sweet Cherry Lam Mukesh K. Jain Mukesh K. Jain |
| author_sort | David R. Sweet |
| collection | DOAJ |
| description | A properly functioning hemovascular system, consisting of circulating innate immune cells and endothelial cells (ECs), is essential in the distribution of nutrients to distant tissues while ensuring protection from invading pathogens. Professional phagocytes (e.g., macrophages) and ECs have co-evolved in vertebrates to adapt to increased physiological demands. Intercellular interactions between components of the hemovascular system facilitate numerous functions in physiology and disease in part through the utilization of shared signaling pathways and factors. Krüppel-like factors (KLFs) 2 and 4 are two such transcription factors with critical roles in both cellular compartments. Decreased expression of either factor in myeloid or endothelial cells increases susceptibility to a multitude of inflammatory diseases, underscoring the essential role for their expression in maintaining cellular quiescence. Given the close evolutionary relationship between macrophages and ECs, along with their shared utilization of KLF2 and 4, we hypothesize that KLF genes evolved in such a way that protected their expression in myeloid and endothelial cells. Within this Perspective, we review the roles of KLF2 and 4 in the hemovascular system and explore evolutionary trends in their nucleotide composition that suggest a coordinated protection that corresponds with the development of mature myeloid and endothelial systems. |
| first_indexed | 2024-12-16T14:27:38Z |
| format | Article |
| id | doaj.art-7293f6e96b06474c855cd3118e55780c |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-16T14:27:38Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-7293f6e96b06474c855cd3118e55780c2022-12-21T22:28:20ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-05-01810.3389/fcvm.2021.645719645719Evolutionary Protection of Krüppel-Like Factors 2 and 4 in the Development of the Mature Hemovascular SystemDavid R. Sweet0David R. Sweet1David R. Sweet2Cherry Lam3Mukesh K. Jain4Mukesh K. Jain5Case Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH, United StatesHarrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesDepartment of Pathology, Case Western Reserve University, Cleveland, OH, United StatesDepartment of Biology, New York University, New York, NY, United StatesCase Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH, United StatesHarrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United StatesA properly functioning hemovascular system, consisting of circulating innate immune cells and endothelial cells (ECs), is essential in the distribution of nutrients to distant tissues while ensuring protection from invading pathogens. Professional phagocytes (e.g., macrophages) and ECs have co-evolved in vertebrates to adapt to increased physiological demands. Intercellular interactions between components of the hemovascular system facilitate numerous functions in physiology and disease in part through the utilization of shared signaling pathways and factors. Krüppel-like factors (KLFs) 2 and 4 are two such transcription factors with critical roles in both cellular compartments. Decreased expression of either factor in myeloid or endothelial cells increases susceptibility to a multitude of inflammatory diseases, underscoring the essential role for their expression in maintaining cellular quiescence. Given the close evolutionary relationship between macrophages and ECs, along with their shared utilization of KLF2 and 4, we hypothesize that KLF genes evolved in such a way that protected their expression in myeloid and endothelial cells. Within this Perspective, we review the roles of KLF2 and 4 in the hemovascular system and explore evolutionary trends in their nucleotide composition that suggest a coordinated protection that corresponds with the development of mature myeloid and endothelial systems.https://www.frontiersin.org/articles/10.3389/fcvm.2021.645719/fullmacrophageendothelial cellKruppel like factorevolutionGC contentmyeloid cell |
| spellingShingle | David R. Sweet David R. Sweet David R. Sweet Cherry Lam Mukesh K. Jain Mukesh K. Jain Evolutionary Protection of Krüppel-Like Factors 2 and 4 in the Development of the Mature Hemovascular System Frontiers in Cardiovascular Medicine macrophage endothelial cell Kruppel like factor evolution GC content myeloid cell |
| title | Evolutionary Protection of Krüppel-Like Factors 2 and 4 in the Development of the Mature Hemovascular System |
| title_full | Evolutionary Protection of Krüppel-Like Factors 2 and 4 in the Development of the Mature Hemovascular System |
| title_fullStr | Evolutionary Protection of Krüppel-Like Factors 2 and 4 in the Development of the Mature Hemovascular System |
| title_full_unstemmed | Evolutionary Protection of Krüppel-Like Factors 2 and 4 in the Development of the Mature Hemovascular System |
| title_short | Evolutionary Protection of Krüppel-Like Factors 2 and 4 in the Development of the Mature Hemovascular System |
| title_sort | evolutionary protection of kruppel like factors 2 and 4 in the development of the mature hemovascular system |
| topic | macrophage endothelial cell Kruppel like factor evolution GC content myeloid cell |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2021.645719/full |
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