{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:02:16Z","timestamp":1787022136151,"version":"build-2736575974"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T00:00:00Z","timestamp":1704153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP22K06834"],"award-info":[{"award-number":["JP22K06834"]}]},{"DOI":"10.13039\/501100004330","name":"Smoking Research Foundation","doi-asserted-by":"publisher","award":["2021G014"],"award-info":[{"award-number":["2021G014"]}],"id":[{"id":"10.13039\/501100004330","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JSPS KAKENHI","award":["JP21K16067"],"award-info":[{"award-number":["JP21K16067"]}]},{"name":"JSPS KAKENHI","award":["JP21K09824"],"award-info":[{"award-number":["JP21K09824"]}]},{"DOI":"10.13039\/100009666","name":"Salt Science Research Foundation","doi-asserted-by":"publisher","award":["2330"],"award-info":[{"award-number":["2330"]}],"id":[{"id":"10.13039\/100009666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009666","name":"Salt Science Research Foundation","doi-asserted-by":"publisher","award":["2135"],"award-info":[{"award-number":["2135"]}],"id":[{"id":"10.13039\/100009666","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Cigarette smoke has been recognized as a major risk factor for cardiovascular disease. However, its direct effects on rodent and human cardiomyocytes and its cellular mechanisms are not fully understood. In this study, we examined the direct effects of cigarette smoke extract (CSE) on contractile functions, intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    dynamics, and mitochondrial function using cultured or freshly isolated rat ventricular myocytes and human induced pluripotent stem cell (iPS)-derived cardiomyocytes. In rat cardiomyocytes, CSE (\u22650.1%) resulted in a time- and concentration-dependent cessation of spontaneous beating of cultured cardiomyocytes, eventually leading to cell death, which indicates direct toxicity. In addition, 1% CSE reduced contractile function of freshly isolated ventricular myocytes. Similar contractile dysfunction (declined spontaneous beating rate and contractility) was also observed in human iPS-derived cardiomyocytes. Regarding intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    dynamics, 1% CSE increased the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transient amplitude by greatly increasing systolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    levels and slightly increasing diastolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    levels. CSE also accelerated the decay of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients, and triggered spike-shaped Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients in some cells. These results indicate that CSE causes abnormal Ca\n                    <jats:sup>2+<\/jats:sup>\n                    dynamics in cardiomyocytes. Furthermore, CSE induced a cascade of mitochondrial dysfunctions, including increased mitochondrial reactive oxygen species, opening of mitochondrial permeability transition pore, reduction of mitochondrial membrane potential, and release of cytochrome c from mitochondria. These results suggest that CSE-induced contractile dysfunction and myocardial cell death is caused by abnormal Ca\n                    <jats:sup>2+<\/jats:sup>\n                    dynamics and subsequent mitochondrial dysregulation, which would result in reduced bioenergetics and activation of cell death pathways.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0295737","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T13:53:00Z","timestamp":1704203580000},"page":"e0295737","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Direct toxicity of cigarette smoke extract on cardiac function mediated by mitochondrial dysfunction in Sprague-Dawley rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes"],"prefix":"10.1371","volume":"19","author":[{"given":"Sakiko","family":"Matsumura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jumpei","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Notomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3204-3921","authenticated-orcid":true,"given":"I-Shan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9991-9428","authenticated-orcid":true,"given":"Daichi","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muneki","family":"Hotomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0086-1022","authenticated-orcid":true,"given":"Tomoe 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