Research Article Small Interfering RNA Targeting Mitochondrial Calcium Uniporter Improves Cardiomyocyte Cell Viability in Hypoxia/Reoxygenation Injury by Reducing Calcium Overload Yuriana Oropeza-Almazán, 1 Eduardo Vázquez-Garza, 1 Héctor Chapoy-Villanueva, 1 Guillermo Torre-Amione, 1,2,3 and Gerardo García-Rivas 1,2 1 C´ atedra de Cardiolog´ ıa y Medicina Vascular, Escuela de Medicina, Tecnol´ ogico de Monterrey, Monterrey, NL, Mexico 2 Centro de Investigaci´ on Biom´ edica, Hospital Zambrano-Hellion, San Pedro Garza-Garc´ ıa, NL, Mexico 3 Methodist DeBakey Heart and Vascular Center, Te Methodist Hospital, Houston, TX, USA Correspondence should be addressed to Gerardo Garc´ ıa-Rivas; gdejesus@itesm.mx Received 6 October 2016; Revised 24 December 2016; Accepted 5 January 2017; Published 27 February 2017 Academic Editor: Leopoldo Aguilera-Aguirre Copyright © 2017 Yuriana Oropeza-Almaz´ an et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Intracellular Ca 2+ mishandling is an underlying mechanism in hypoxia/reoxygenation (H/R) injury that results in mitochondrial dysfunction and cardiomyocytes death. Tese events are mediated by mitochondrial Ca 2+ (mCa 2+ ) overload that is facilitated by the mitochondrial calcium uniporter (MCU) channel. Along this line, we evaluated the efect of siRNA-targeting MCU in cardiomyocytes subjected to H/R injury. First, cardiomyocytes treated with siRNA demonstrated a reduction of MCU expression by 67%, which resulted in signifcant decrease in mitochondrial Ca 2+ transport. siRNA treated cardiomyocytes showed decreased mitochondrial permeability pore opening and oxidative stress trigger by Ca 2+ overload. Furthermore, afer H/R injury MCU silencing decreased necrosis and apoptosis levels by 30% and 50%, respectively, and resulted in reduction in caspases 3/7, 9, and 8 activity. Our fndings are consistent with previous conclusions that demonstrate that MCU activity is partly responsible for cellular injury induced by H/R and support the concept of utilizing siRNA-targeting MCU as a potential therapeutic strategy. 1. Introduction Coronary heart disease (CHD) is the leading cause of death in industrialized and third-world countries [1]. Te efects of CHD are associated with the negative efects of ischemia- reperfusion. Ischemia-reperfusion injury normally arises in patients presenting myocardial infarction with acute ST- segment elevation in which timely and efective myocardial reperfusion is limiting the infarct size and death. However, several events that appear during myocardial reperfusion can induce further cell damage in a phenomenon known as reperfusion injury [2]. Numerous experimental studies have identifed some critical factors that act in concert to mediate the unfavorable efects of reperfusion injury. First, intracellular and mito- chondrial Ca 2+ (mCa 2+ ) overload are exacerbated during reperfusion due to oxidative stress-induced disruption of the sarcolemma and sarcoplasmic reticulum membranes [3]. Second, mitochondrial reenergization during reoxygenation allows the recovery of the membrane potential that drives the Ca 2+ uptake into the mitochondria through the mito- chondrial Ca 2+ uniporter (MCU) channel and subsequently induces mCa 2+ overload [4]. Tese events result in mito- chondrial dysfunction, leading to cardiomyocyte death by the opening of the mitochondrial transition pore (  PTP) [5]. Accordingly, targeting oxidative stress and/or modulating the activity of MCU by a selective blocker such as Ru 360 [6, 7] or the inhibition of  PTP opening by cyclosporine A (CsA) provide specifc targets for intervention [8]. Te role of MCU in the regulation of mCa 2+ overload is supported by the observations that, in a model of cardiac Hindawi Oxidative Medicine and Cellular Longevity Volume 2017, Article ID 5750897, 13 pages https://doi.org/10.1155/2017/5750897