The pleiotropic effects of GATA2 on atheroma development

Abstract

Atherosclerosis is a chronic inflammatory disease driven by complex interactions between vascular cells and the immune system. Transcriptional regulation plays a significant role in coordinating these interactions; however, how key transcription factors contribute to these processes remains unknown. GATA binding protein 2 (GATA2), a zinc-finger transcription factor essential for hematopoiesis, has recently emerged as an important regulator of both vascular and immune cell function in atherogenesis. Additionally, genetic variation in the GATA2 gene is associated with hematologic, inflammatory, and cardiovascular disease, underscoring its broad relevance to human pathology. This review summarizes the pleiotropic roles of GATA2 in atherosclerosis, highlighting its impact across multiple cell types. In macrophages, GATA2 overexpression promotes proliferation, impairs efferocytosis, and disrupts lipid handling, contributing to foam cell formation and necrotic core development. In vascular smooth muscle cells, GATA2 is implicated in phenotypic switching and transdifferentiation to macrophage-like cells, while in endothelial cells it regulates pathways involved in vascular permeability, inflammation, and angiogenesis. Collectively, this work positions GATA2 as a central transcriptional regulator linking immune dysfunction, vascular remodelling, and disease progression in atherosclerosis. Therefore, targeting GATA2 or GATA2-dependent pathways could represent a promising avenue for therapeutic development.