Md Shenuarin Bhuiyan1, Kohji Fukunaga. 1. Tohoku University, Graduate School of Pharmaceutical Sciences, Department of Pharmacology, Aramaki-Aoba, Aoba-ku, Sendai 980-8578, Japan.
Abstract
OBJECTIVE: Decreased dehydroepiandrosterone (DHEA) levels are associated with endothelial dysfunction and increased cardiovascular mortality in postmenopausal women. We investigated the role of DHEA, also known as sigma-1 receptor (Sig-1R) agonist, in myocardial hypertrophy, cardiac functional recovery and defined mechanisms of cardioprotective action. METHODS: Wistar rats subjected to bilateral ovariectomy (OVX) were further treated with abdominal aortic stenosis. DHEA (15 and 30 mg/kg) was administered orally once a day for 14 days starting from 2 weeks after aortic banding. RESULTS: Time course study indicated that left ventricle (LV) weight:body weight (BW) ratio increased time-dependently from 1 to 4 weeks after pressure-overload (PO) with significant inversed regulation of Sig-1R expression. Treatment with the Sig-1R agonist, DHEA, significantly attenuated PO-induced myocardial hypertrophy with increased expression of Sig-1R in the LV. DHEA also attenuated hypertrophy-induced impaired LV end diastolic pressure, LV developed pressure and LV contractility (+/- dp/dt(max)). DHEA treatment significantly restored PO-induced impaired eNOS and Akt activity in the LV. CONCLUSION: We report, for the first time to our knowledge, the potential role of Sig-1R expression in the heart to attenuate PO-induced hypertrophy in ovariectomized rats. DHEA treatment protects against PO-induced cardiac injury via upregulation of Sig-1R and stimulation of Sig-1R-mediated Akt-eNOS signaling.
OBJECTIVE: Decreased dehydroepiandrosterone (DHEA) levels are associated with endothelial dysfunction and increased cardiovascular mortality in postmenopausal women. We investigated the role of DHEA, also known as sigma-1 receptor (Sig-1R) agonist, in myocardial hypertrophy, cardiac functional recovery and defined mechanisms of cardioprotective action. METHODS:Wistar rats subjected to bilateral ovariectomy (OVX) were further treated with abdominal aortic stenosis. DHEA (15 and 30 mg/kg) was administered orally once a day for 14 days starting from 2 weeks after aortic banding. RESULTS: Time course study indicated that left ventricle (LV) weight:body weight (BW) ratio increased time-dependently from 1 to 4 weeks after pressure-overload (PO) with significant inversed regulation of Sig-1R expression. Treatment with the Sig-1R agonist, DHEA, significantly attenuated PO-induced myocardial hypertrophy with increased expression of Sig-1R in the LV. DHEA also attenuated hypertrophy-induced impaired LV end diastolic pressure, LV developed pressure and LV contractility (+/- dp/dt(max)). DHEA treatment significantly restored PO-induced impaired eNOS and Akt activity in the LV. CONCLUSION: We report, for the first time to our knowledge, the potential role of Sig-1R expression in the heart to attenuate PO-induced hypertrophy in ovariectomized rats. DHEA treatment protects against PO-induced cardiac injury via upregulation of Sig-1R and stimulation of Sig-1R-mediated Akt-eNOS signaling.
Authors: Richa Aishwarya; Chowdhury S Abdullah; Naznin S Remex; Shafiul Alam; Mahboob Morshed; Sadia Nitu; Brandon Hartman; Judy King; Mohammad Alfrad Nobel Bhuiyan; A Wayne Orr; Christopher G Kevil; Md Shenuarin Bhuiyan Journal: Am J Pathol Date: 2021-10-25 Impact factor: 4.307
Authors: José Alexandre Salerno; Thayana Torquato; Jairo R Temerozo; Livia Goto-Silva; Karina Karmirian; Mayara A Mendes; Carolina Q Sacramento; Natalia Fintelman-Rodrigues; Letícia R Q Souza; Isis M Ornelas; Carla P Veríssimo; Luiz Guilherme H S Aragão; Gabriela Vitória; Carolina S G Pedrosa; Suelen da Silva Gomes Dias; Vinicius Cardoso Soares; Teresa Puig-Pijuan; Vinícius Salazar; Rafael Dariolli; Diogo Biagi; Daniel R Furtado; Luciana Barreto Chiarini; Helena L Borges; Patrícia T Bozza; Marilia Zaluar P Guimarães; Thiago M L Souza; Stevens K Rehen Journal: PeerJ Date: 2021-12-20 Impact factor: 2.984
Authors: Chowdhury S Abdullah; Shafiul Alam; Richa Aishwarya; Sumitra Miriyala; Manikandan Panchatcharam; Mohammad Alfrad Nobel Bhuiyan; Jonette M Peretik; A Wayne Orr; Jeanne James; Hanna Osinska; Jeffrey Robbins; John N Lorenz; Md Shenuarin Bhuiyan Journal: J Am Heart Assoc Date: 2018-10-16 Impact factor: 5.501