The FOX transcription factors regulate vascular pathology, diabetes and Tregs

Abstract

A small number of upstream master genes in "higher hierarchy" controls the expression of a large number of downstream genes and integrates the signaling pathways underlying the pathogenesis of cardiovascular diseases with or without autoimmune inflammatory mechanisms. In this brief review, we organize our analysis of recent progress in characterization of forkhead (FOX) transcription factor family members in vascular pathology, diabetes and regulatory T cells into the following sections: (1) Overview of the FOX transcription factor superfamily; (2) Vascular pathology of mice deficient in FOX transcription factors; (3) Roles of FOX transcription factors in endothelial cell pathology; (4) Roles of FOX transcription factors in vascular smooth muscle cells; (5) Roles of FOX transcription factors in the pathogenesis of diabetes; and (6) Immune system phenotypes of mice deficient in FOX transcription factors. Advances in these areas suggest that the FOX transcription factor family plays important roles in vascular development and in the pathogenesis of autoimmune inflammatory cardiovascular diseases.

Figure 1. FOX transcription factors in endothelial cells

Various FOX transcription factors affect endothelial cell (EC) and endothelial progenitor cell (EPC) growth and apoptosis.

Figure 2. FOX transcription factors in immune responses and inflammation

Various FOX transcription factors mediate immune responses that regulate inflammation. Dashed lines represent pathways that do not necessarily produce inflammation. PAI-1 Plasminogen Activator Inhibitor-1, NF-κB Nuclear Factor-κB.