The BRD4-DOT1L axis in vascular smooth muscle cell phenotypic transitions and cardiovascular diseases

The smooth muscle cell (SMC) is crucial for maintaining vascular function and homeostasis. SMCs exhibit remarkable plasticity, enabling them to undergo phenotypic transitions in response to various stimulations. These transitions are implicated in the pathogenesis of cardiovascular diseases which pose significant health challenges in the United States. Increasingly, studies reveal that epigenetic modifications are actively involved in SMC phenotypic transitions; however, the mechanistic understanding of how epigenetic regulations influence these transitions in cardiovascular diseases is still limited. This dissertation focuses on two potential epigenetic regulators, bromodomain-containing protein 4 (BRD4) and DOT1 like histone lysine methyltransferase (DOT1L). Our central hypothesis is that the BRD4-DOT1L are the functional major epigenetic regulators that stimulate SMC phenotype changes, thereby promoting cardiovascular diseases.