Biochemistry & Pharmacology: Open Access
Open Access

Abstract

Nuclear Factor Erythroid 2-Related Factor 2 is Activated by Rosuvastatin via p21cip1 Upregulation in Endothelial Cells

Chieko Ihoriya, Minoru Satoh, Norio Komai, Tamaki Sasaki and Naoki Kashihara

Oxidative stress is a key component in the development of cardiovascular diseases and chronic kidney diseases. Statins have cardio-protective activity, and previous reports have indicated that they activate nuclear factor erythroid 2-related factor 2 (Nrf2), although their molecular mechanism is unknown. Nrf2 is an oxidative stress-responsive transcription factor with a crucial role in cellular defense against oxidative stress. We investigated the molecular mechanisms of Nrf2 activation by rosuvastatin. Nrf2 activity and Nrf2-mediated antioxidant gene expression were upregulated by rosuvastatin in human umbilical vein endothelial cells. Rosuvastatin increased Nrf2 protein levels by reducing Nrf2 degradation and upregulating the interaction between Nrf2 and p21Cip1, which was inhibited by p21Cip1- targeted siRNA. Rosuvastatin-mediated activation of endothelial Nrf2 provides a possible therapeutic alternative for cardiovascular diseases.