The Counter-Regulatory Effects of ESE-1 During Angiotensin II-Mediated Vascular Inflammation and Remodeling

Abstract

Angiotensin II (Ang II) is a critical mediator vascular inflammation and remodeling in a number of diseases including hypertension and atherosclerosis. The purpose of this study was to evaluate the role of the epithelium-specific ETS transcription factor-1 (ESE-1), a member of E26 transformation-specific sequence (ETS) transcription factors, as a mediator of Ang II-mediated vascular responses. ESE-1 knockout mice were used to evaluate the role of ESE-1 in regulating Ang II-mediated vascular inflammation and remodeling. ESE-1 levels are low to undetectable under basal conditions but rapidly increase in response to Ang II. Intimal medial thickness and perivascular fibrosis of the aorta were significantly greater in ESE-1 knockout mice compared with the wild-type littermate controls. Proliferating cell nuclear antigen (PCNA) staining was also greater in the aorta of the Ang II-infused ESE-1 knockout mice compared with the controls. The infiltration of T cells and macrophage into the vessel wall of the aorta was dramatically enhanced in the ESE-1 knockout mice compared with the controls. Finally, Ang II-induced expression of a known downstream target of ESE-1, nitric oxide synthase 2 (NOS2), was significantly blunted in ESE-1 knockout mice compared to littermate controls. The alterations in vascular inflammation and remodeling were associated with an exaggerated systolic blood pressure response to Ang II in ESE-1 knockout mice. ESE-1 is an Ang II-inducible transcription factor that plays an important counter-regulatory role in the setting of vascular inflammation and remodeling.