Sweet David R, Lam Cherry, Jain Mukesh K
Case Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH, United States.
Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States.
Front Cardiovasc Med. 2021 May 17;8:645719. doi: 10.3389/fcvm.2021.645719. eCollection 2021.
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.
一个正常运作的血管系统，由循环的固有免疫细胞和内皮细胞（ECs）组成，在将营养物质输送到远处组织的同时确保抵御入侵病原体，这一点至关重要。专业吞噬细胞（如巨噬细胞）和内皮细胞在脊椎动物中共同进化，以适应不断增加的生理需求。血管系统各组成部分之间的细胞间相互作用部分通过利用共享的信号通路和因子，促进了生理学和疾病中的多种功能。Krüppel样因子（KLFs）2和4就是这样两种在两个细胞区室中都起关键作用的转录因子。髓系细胞或内皮细胞中任一因子的表达降低都会增加对多种炎症性疾病的易感性，这突出了它们的表达在维持细胞静止中的重要作用。鉴于巨噬细胞和内皮细胞之间密切的进化关系，以及它们对KLF2和4的共同利用，我们推测KLF基因的进化方式保护了它们在髓系细胞和内皮细胞中的表达。在本观点中，我们回顾了KLF2和4在血管系统中的作用，并探讨了它们核苷酸组成的进化趋势，这些趋势表明存在一种与成熟髓系和内皮系统发育相对应的协同保护机制。
