Nan-Qian Zhou1, Ning Liu2, Peng Li3, Song Ping3, Qi-Sheng Peng4, Wei-Dong Shi1. 1. a Department of Ultrasound, China-Japan Union Hospital , Jilin University , Changchun , China. 2. b Central Laboratory, the Second Hospital , Jilin University , Changchun , China. 3. c Department of Pharmacology, College of Pharmacy , Xinxiang Medical University , Xinxiang , China. 4. d Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis , Jilin University , Changchun , China.
Abstract
BACKGROUND: Hypertension is an increased risk of heart failure and acute myocardial infarction (MI). Tert-butylhydroquinone (tBHQ), as an antioxidant, shows multiple cardioprotective actions including the reduction in blood pressure. The aim of this study was to investigate whether and how tBHQ improves heart functions in rats. METHODS: The MI model was established in WKY and spontaneously hypertensive rats (SHRs) by ligation of left anterior descending coronary artery. Akt phosphorylation was examined by western blot in human umbilical vein endothelial cells (HUVECs) or in rats. Angiogenesis was assessed by immunohistochemistry and immunofluorescence. Heart function was determined by echocardiography. RESULTS: tBHQ increased Akt phosphorylation, promoted cell proliferations and migrations in HUVECs, which were abolished by Akt inhibitor wortmannin. In SHRs following MI, administration of tBHQ significantly increased Akt phosphorylation, promoted angiogenesis, reduced infarct size, and improved heart functions after 14 postoperative days. Importantly, these in vivo effects of tBHQ were ablated by wortmannin in SHRs. CONCLUSION: tBHQ via Akt activation promotes ischemia-induced angiogenesis and improves heart functions in hypertensive rats. In perspectives, the application of tBHQ should be considered in patients with ischemic diseases such as MI and stroke.
BACKGROUND:Hypertension is an increased risk of heart failure and acute myocardial infarction (MI). Tert-butylhydroquinone (tBHQ), as an antioxidant, shows multiple cardioprotective actions including the reduction in blood pressure. The aim of this study was to investigate whether and how tBHQ improves heart functions in rats. METHODS: The MI model was established in WKY and spontaneously hypertensiverats (SHRs) by ligation of left anterior descending coronary artery. Akt phosphorylation was examined by western blot in human umbilical vein endothelial cells (HUVECs) or in rats. Angiogenesis was assessed by immunohistochemistry and immunofluorescence. Heart function was determined by echocardiography. RESULTS:tBHQ increased Akt phosphorylation, promoted cell proliferations and migrations in HUVECs, which were abolished by Akt inhibitor wortmannin. In SHRs following MI, administration of tBHQ significantly increased Akt phosphorylation, promoted angiogenesis, reduced infarct size, and improved heart functions after 14 postoperative days. Importantly, these in vivo effects of tBHQ were ablated by wortmannin in SHRs. CONCLUSION:tBHQ via Akt activation promotes ischemia-induced angiogenesis and improves heart functions in hypertensiverats. In perspectives, the application of tBHQ should be considered in patients with ischemic diseases such as MI and stroke.
Authors: Iolanda Lazaro; Laura Lopez-Sanz; Susana Bernal; Ainhoa Oguiza; Carlota Recio; Ana Melgar; Luna Jimenez-Castilla; Jesus Egido; Julio Madrigal-Matute; Carmen Gomez-Guerrero Journal: Front Pharmacol Date: 2018-07-31 Impact factor: 5.810