Kruppel-Like Factors in Thrombosis and Hemostasis

Armed with the appreciation that the blood and vascular system share common origins and cooperate to ensure fundamental processes (e.g. blood flow/fluidity, oxygen/nutrient delivery, immunity) essential for organismal survival, we posited that shared molecular pathways may be operative in coordinating the function of both systems. Over the past 2 decades, studies from our group and others have identified a family of transcription factors termed Kruppel-like factors (KLFs) as essential for development, differentiation, and function of cellular constituents of both the hematopoietic and vascular systems. In this presentation, discussion will focus on the role KLFs in control of endothelium and myeloid cell biology in physiology and disease. Specifically, cellular and in vivo evidence will be discussed implicating KLFs as master regulators of all cardinal endothelial functions (permeability, vasoreactivity, blood fluidity, and inflammation). Further, studies demonstrating KLF-control of myeloid cell development, subset specification, and pro-inflammatory activation will be reviewed with particular emphasis on results of efforts altering myeloid KLFs in the context of acute (e.g. bacterial infection, sepsis) and chronic (e.g. atherosclerosis, arterial/venous thrombosis) inflammatory processes. Correlative studies in human subjects will be presented. And finally, insights into how targeting KLFs can be exploited for therapeutic gain will be discussed.