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Silicon dioxide (SiO<jats:sub>2<\/jats:sub>) has emerged as a promising therapy vector for the heart. However, its potential toxicity and mechanisms of damage remain poorly understood. This study provides the first exploration of SiO<jats:sub>2<\/jats:sub>-induced toxicity in cultured cardiomyocytes exposed to 7- or 670-nm SiO<jats:sub>2<\/jats:sub> particles. We evaluated the mechanism of cell death in isolated adult cardiomyocytes exposed to 24-h incubation. The SiO<jats:sub>2<\/jats:sub> cell membrane association and internalization were analyzed. SiO<jats:sub>2<\/jats:sub> showed a dose-dependent cytotoxic effect with a half-maximal inhibitory concentration for the 7 nm (99.5 \u00b1 12.4 \u00b5g\/ml) and 670 nm (&gt;1,500 \u00b5g\/ml) particles, which indicates size-dependent toxicity. We evaluated cardiomyocyte shortening and intracellular Ca<jats:sup>2+<\/jats:sup> handling, which showed impaired contractility and intracellular Ca<jats:sup>2+<\/jats:sup> transient amplitude during \u03b2-adrenergic stimulation in SiO<jats:sub>2<\/jats:sub> treatment. The time to 50% Ca<jats:sup>2+<\/jats:sup> decay increased 39%, and the Ca<jats:sup>2+<\/jats:sup> spark frequency and amplitude decreased by 35 and 21%, respectively, which suggest a reduction in sarcoplasmic reticulum Ca<jats:sup>2+<\/jats:sup>-ATPase (SERCA) activity. Moreover, SiO<jats:sub>2<\/jats:sub> treatment depolarized the mitochondrial membrane potential and decreased ATP production by 55%. Notable glutathione depletion and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> generation were also observed. These data indicate that SiO<jats:sub>2<\/jats:sub> increases oxidative stress, which leads to mitochondrial dysfunction and low energy status; these underlie reduced SERCA activity, shortened Ca<jats:sup>2+<\/jats:sup> release, and reduced cell shortening. This mechanism of SiO<jats:sub>2<\/jats:sub> cardiotoxicity potentially plays an important role in the pathophysiology mechanism of heart failure, arrhythmias, and sudden death. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Silica particles are used as novel nanotechnology-based vehicles for diagnostics and therapeutics for the heart. However, their potential hazardous effects remain unknown. Here, the cardiotoxicity of silica nanoparticles in rat myocytes has been described for the first time, showing an impairment of mitochondrial function that interfered directly with Ca<jats:sup>2+<\/jats:sup> handling. <\/jats:p>","DOI":"10.1152\/ajpheart.00564.2016","type":"journal-article","created":{"date-parts":[[2017,1,27]],"date-time":"2017-01-27T22:10:19Z","timestamp":1485555019000},"page":"H645-H661","source":"Crossref","is-referenced-by-count":66,"title":["Silica nanoparticles induce cardiotoxicity interfering with energetic status and Ca<sup>2+<\/sup> handling in adult rat cardiomyocytes"],"prefix":"10.1152","volume":"312","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5001-0093","authenticated-orcid":false,"given":"Carlos Enrique","family":"Guerrero-Beltr\u00e1n","sequence":"first","affiliation":[{"name":"C\u00e1tedra de Cardiolog\u00eda y Medicina Vascular, Escuela Nacional de Medicina, Tecnol\u00f3gico de Monterrey, Monterrey, M\u00e9xico;"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica, Hospital Zambrano-Hellion, Tecnol\u00f3gico de Monterrey, San Pedro Garza-Garc\u00eda, M\u00e9xico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Bernal-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Cardiolog\u00eda y Medicina Vascular, Escuela Nacional de Medicina, Tecnol\u00f3gico de Monterrey, Monterrey, M\u00e9xico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Lozano","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Cardiolog\u00eda y Medicina Vascular, Escuela Nacional de Medicina, Tecnol\u00f3gico de Monterrey, Monterrey, M\u00e9xico;"},{"name":"Namur Nanosafety Centre, Namur Research Institute for Life Sciences, Research Centre for the Physics of Matter and Radiation, University of Namur, Namur, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuriana","family":"Oropeza-Almaz\u00e1n","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Cardiolog\u00eda y Medicina Vascular, Escuela Nacional de Medicina, Tecnol\u00f3gico de Monterrey, Monterrey, M\u00e9xico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Cristina","family":"Castillo","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Cardiolog\u00eda y Medicina Vascular, Escuela Nacional de Medicina, Tecnol\u00f3gico de Monterrey, Monterrey, M\u00e9xico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas Roberto","family":"Garza","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Cardiolog\u00eda y Medicina Vascular, Escuela Nacional de Medicina, Tecnol\u00f3gico de Monterrey, Monterrey, M\u00e9xico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noem\u00ed","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Cardiolog\u00eda y Medicina Vascular, Escuela Nacional de Medicina, Tecnol\u00f3gico de Monterrey, Monterrey, M\u00e9xico;"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica, Hospital Zambrano-Hellion, Tecnol\u00f3gico de Monterrey, San Pedro Garza-Garc\u00eda, M\u00e9xico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Vela","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Cardiolog\u00eda y Medicina Vascular, Escuela Nacional de Medicina, Tecnol\u00f3gico de Monterrey, Monterrey, M\u00e9xico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7794-135X","authenticated-orcid":false,"given":"Alejandra","family":"Garc\u00eda-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Materiales Avanzados S.C. 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