Systems toxicology study reveals reduced impact of heated tobacco product aerosol extract relative to cigarette smoke on premature aging and exacerbation effects in aged aortic cells in vitro
Aging and smoking are major risk factors for cardiovascular diseases (CVD). Our in vitro study compared, in the context of aging, the effects of the aerosol of Tobacco Heating System 2.2 (THS; an electrically heated tobacco product) and 3R4F reference cigarette smoke (CS) on processes that contribut...
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| Veröffentlicht in: | Archives of toxicology 2021-10, Vol.95 (10), p.3341-3359 |
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| creator | Poussin, Carine van der Toorn, Marco Scheuner, Sophie Piault, Romain Kondylis, Athanasios Savioz, Rebecca Dulize, Rémi Peric, Dariusz Guedj, Emmanuel Maranzano, Fabio Merg, Celine Morelli, Moran Egesipe, Anne-Laure Johne, Stéphanie Majeed, Shoaib Pak, Claudius Schneider, Thomas Schlage, Walter K. Ivanov, Nikolai V. Peitsch, Manuel C. Hoeng, Julia |
| description | Aging and smoking are major risk factors for cardiovascular diseases (CVD). Our in vitro study compared, in the context of aging, the effects of the aerosol of Tobacco Heating System 2.2 (THS; an electrically heated tobacco product) and 3R4F reference cigarette smoke (CS) on processes that contribute to vascular pathomechanisms leading to CVD. Young and old human aortic smooth muscle cells (HAoSMC) were exposed to various concentrations of aqueous extracts (AE) from 3R4F CS [0.014–0.22 puffs/mL] or THS aerosol [0.11–1.76 puffs/mL] for 24 h. Key markers were measured by high-content imaging, transcriptomics profiling and multianalyte profiling. In our study, in vitro aging increased senescence, DNA damage, and inflammation and decreased proliferation in the HAoSMCs. At higher concentrations of 3R4F AE, young HAoSMCs behaved similarly to aged cells, while old HAoSMCs showed additional DNA damage and apoptosis effects. At 3R4F AE concentrations with the maximum effect, the THS AE showed no significant effect in young or old HAoSMCs. It required an approximately ten-fold higher concentration of THS AE to induce effects similar to those observed with 3R4F. These effects were independent of nicotine, which did not show a significant effect on HAoSMCs at any tested concentration. Our results show that 3R4F AE accelerates aging in young HAoSMCs and exacerbates the aging effect in old HAoSMCs in vitro, consistent with CS-related contributions to the risk of CVD. Relative to 3R4F AE, the THS AE showed a significantly reduced impact on HAoSMCs, suggesting its lower risk for vascular SMC-associated pathomechanisms leading to CVD. |
| doi_str_mv | 10.1007/s00204-021-03123-y |
| format | Article |
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Our in vitro study compared, in the context of aging, the effects of the aerosol of Tobacco Heating System 2.2 (THS; an electrically heated tobacco product) and 3R4F reference cigarette smoke (CS) on processes that contribute to vascular pathomechanisms leading to CVD. Young and old human aortic smooth muscle cells (HAoSMC) were exposed to various concentrations of aqueous extracts (AE) from 3R4F CS [0.014–0.22 puffs/mL] or THS aerosol [0.11–1.76 puffs/mL] for 24 h. Key markers were measured by high-content imaging, transcriptomics profiling and multianalyte profiling. In our study, in vitro aging increased senescence, DNA damage, and inflammation and decreased proliferation in the HAoSMCs. At higher concentrations of 3R4F AE, young HAoSMCs behaved similarly to aged cells, while old HAoSMCs showed additional DNA damage and apoptosis effects. At 3R4F AE concentrations with the maximum effect, the THS AE showed no significant effect in young or old HAoSMCs. It required an approximately ten-fold higher concentration of THS AE to induce effects similar to those observed with 3R4F. These effects were independent of nicotine, which did not show a significant effect on HAoSMCs at any tested concentration. Our results show that 3R4F AE accelerates aging in young HAoSMCs and exacerbates the aging effect in old HAoSMCs in vitro, consistent with CS-related contributions to the risk of CVD. Relative to 3R4F AE, the THS AE showed a significantly reduced impact on HAoSMCs, suggesting its lower risk for vascular SMC-associated pathomechanisms leading to CVD.</description><identifier>ISSN: 0340-5761</identifier><identifier>ISSN: 1432-0738</identifier><identifier>EISSN: 1432-0738</identifier><identifier>DOI: 10.1007/s00204-021-03123-y</identifier><identifier>PMID: 34313809</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Aerosols ; Aging ; Aging, Premature - etiology ; Aorta ; Aorta - cytology ; Aorta - drug effects ; Apoptosis ; Apoptosis - drug effects ; Biomedical and Life Sciences ; Biomedicine ; Cardiovascular diseases ; Cell Proliferation - drug effects ; Cells, Cultured ; Cellular Senescence ; Cigarette smoke ; Cigarettes ; Damage ; Deoxyribonucleic acid ; DNA ; DNA damage ; DNA Damage - drug effects ; Environmental Health ; Health risks ; Humans ; Inflammation - etiology ; Muscles ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - pathology ; Nicotine ; Occupational Medicine/Industrial Medicine ; Organ Toxicity and Mechanisms ; Pharmacology/Toxicology ; Risk analysis ; Risk factors ; Senescence ; Smoke ; Smoke - adverse effects ; Smoking - adverse effects ; Smooth muscle ; Tobacco ; Tobacco Products ; Toxicology</subject><ispartof>Archives of toxicology, 2021-10, Vol.95 (10), p.3341-3359</ispartof><rights>The Author(s) 2021</rights><rights>2021. The Author(s).</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-857a8ac1fcf5a8b30a800fb838acface65534c0deb19d3f405017bda62107c0e3</citedby><cites>FETCH-LOGICAL-c474t-857a8ac1fcf5a8b30a800fb838acface65534c0deb19d3f405017bda62107c0e3</cites><orcidid>0000-0001-9729-6853</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00204-021-03123-y$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00204-021-03123-y$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34313809$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Poussin, Carine</creatorcontrib><creatorcontrib>van der Toorn, Marco</creatorcontrib><creatorcontrib>Scheuner, Sophie</creatorcontrib><creatorcontrib>Piault, Romain</creatorcontrib><creatorcontrib>Kondylis, Athanasios</creatorcontrib><creatorcontrib>Savioz, Rebecca</creatorcontrib><creatorcontrib>Dulize, Rémi</creatorcontrib><creatorcontrib>Peric, Dariusz</creatorcontrib><creatorcontrib>Guedj, Emmanuel</creatorcontrib><creatorcontrib>Maranzano, Fabio</creatorcontrib><creatorcontrib>Merg, Celine</creatorcontrib><creatorcontrib>Morelli, Moran</creatorcontrib><creatorcontrib>Egesipe, Anne-Laure</creatorcontrib><creatorcontrib>Johne, Stéphanie</creatorcontrib><creatorcontrib>Majeed, Shoaib</creatorcontrib><creatorcontrib>Pak, Claudius</creatorcontrib><creatorcontrib>Schneider, Thomas</creatorcontrib><creatorcontrib>Schlage, Walter K.</creatorcontrib><creatorcontrib>Ivanov, Nikolai V.</creatorcontrib><creatorcontrib>Peitsch, Manuel C.</creatorcontrib><creatorcontrib>Hoeng, Julia</creatorcontrib><title>Systems toxicology study reveals reduced impact of heated tobacco product aerosol extract relative to cigarette smoke on premature aging and exacerbation effects in aged aortic cells in vitro</title><title>Archives of toxicology</title><addtitle>Arch Toxicol</addtitle><addtitle>Arch Toxicol</addtitle><description>Aging and smoking are major risk factors for cardiovascular diseases (CVD). Our in vitro study compared, in the context of aging, the effects of the aerosol of Tobacco Heating System 2.2 (THS; an electrically heated tobacco product) and 3R4F reference cigarette smoke (CS) on processes that contribute to vascular pathomechanisms leading to CVD. Young and old human aortic smooth muscle cells (HAoSMC) were exposed to various concentrations of aqueous extracts (AE) from 3R4F CS [0.014–0.22 puffs/mL] or THS aerosol [0.11–1.76 puffs/mL] for 24 h. Key markers were measured by high-content imaging, transcriptomics profiling and multianalyte profiling. In our study, in vitro aging increased senescence, DNA damage, and inflammation and decreased proliferation in the HAoSMCs. At higher concentrations of 3R4F AE, young HAoSMCs behaved similarly to aged cells, while old HAoSMCs showed additional DNA damage and apoptosis effects. At 3R4F AE concentrations with the maximum effect, the THS AE showed no significant effect in young or old HAoSMCs. It required an approximately ten-fold higher concentration of THS AE to induce effects similar to those observed with 3R4F. These effects were independent of nicotine, which did not show a significant effect on HAoSMCs at any tested concentration. Our results show that 3R4F AE accelerates aging in young HAoSMCs and exacerbates the aging effect in old HAoSMCs in vitro, consistent with CS-related contributions to the risk of CVD. Relative to 3R4F AE, the THS AE showed a significantly reduced impact on HAoSMCs, suggesting its lower risk for vascular SMC-associated pathomechanisms leading to CVD.</description><subject>Aerosols</subject><subject>Aging</subject><subject>Aging, Premature - etiology</subject><subject>Aorta</subject><subject>Aorta - cytology</subject><subject>Aorta - drug effects</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cardiovascular diseases</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Cellular Senescence</subject><subject>Cigarette smoke</subject><subject>Cigarettes</subject><subject>Damage</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage</subject><subject>DNA Damage - drug effects</subject><subject>Environmental Health</subject><subject>Health risks</subject><subject>Humans</subject><subject>Inflammation - etiology</subject><subject>Muscles</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - pathology</subject><subject>Nicotine</subject><subject>Occupational Medicine/Industrial Medicine</subject><subject>Organ Toxicity and Mechanisms</subject><subject>Pharmacology/Toxicology</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Senescence</subject><subject>Smoke</subject><subject>Smoke - adverse effects</subject><subject>Smoking - adverse effects</subject><subject>Smooth muscle</subject><subject>Tobacco</subject><subject>Tobacco Products</subject><subject>Toxicology</subject><issn>0340-5761</issn><issn>1432-0738</issn><issn>1432-0738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9ks1u1TAQhS0EoqXwAiyQJTZsAuPYSZwNEqr4kyqxANaW40xSlyS-2M5V83S8GnN7S_lZsBpp_J2ZOdZh7KmAlwKgeZUASlAFlKIAKUpZbPfYqVCyLKCR-j47BamgqJpanLBHKV0BiFK38iE7kUoKqaE9ZT8-bynjnHgO196FKYwbT3ntNx5xj3ZKVPvVYc_9vLMu8zDwS7SZGjl01rnAdzEQkbnFGFKYOF7neCAjTjb7PRLInR9txJyRpzl8Qx4WkuFs8xqR29EvI7dLT1LrMHYkIwCHAV1O3C9E0D4bYvaOO5ymm-be5xgeswcDXYlPbusZ-_ru7ZfzD8XFp_cfz99cFE41Khe6aqy2TgxuqKzuJFgNMHRaUnOgnXVVSeWgx060vRwUVCCarrd1KaBxgPKMvT7O3a3djL3DhUxOZhf9bONmgvXm75fFX5ox7I1WStetogEvbgfE8H3FlM3s08GLXTCsyZRVVdWyqaEi9Pk_6FVY40L2iGpkLWvVtkSVR8rRt6eIw90xAswhH-aYD0P5MDf5MBuJnv1p407yKxAEyCOQ6GkZMf7e_Z-xPwFqBs1E</recordid><startdate>20211001</startdate><enddate>20211001</enddate><creator>Poussin, Carine</creator><creator>van der Toorn, Marco</creator><creator>Scheuner, Sophie</creator><creator>Piault, Romain</creator><creator>Kondylis, Athanasios</creator><creator>Savioz, Rebecca</creator><creator>Dulize, Rémi</creator><creator>Peric, Dariusz</creator><creator>Guedj, Emmanuel</creator><creator>Maranzano, Fabio</creator><creator>Merg, Celine</creator><creator>Morelli, Moran</creator><creator>Egesipe, Anne-Laure</creator><creator>Johne, Stéphanie</creator><creator>Majeed, Shoaib</creator><creator>Pak, Claudius</creator><creator>Schneider, Thomas</creator><creator>Schlage, Walter K.</creator><creator>Ivanov, Nikolai V.</creator><creator>Peitsch, Manuel C.</creator><creator>Hoeng, Julia</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T2</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>MBDVC</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9729-6853</orcidid></search><sort><creationdate>20211001</creationdate><title>Systems toxicology study reveals reduced impact of heated tobacco product aerosol extract relative to cigarette smoke on premature aging and exacerbation effects in aged aortic cells in vitro</title><author>Poussin, Carine ; van der Toorn, Marco ; Scheuner, Sophie ; Piault, Romain ; Kondylis, Athanasios ; Savioz, Rebecca ; Dulize, Rémi ; Peric, Dariusz ; Guedj, Emmanuel ; Maranzano, Fabio ; Merg, Celine ; Morelli, Moran ; Egesipe, Anne-Laure ; Johne, Stéphanie ; Majeed, Shoaib ; Pak, Claudius ; Schneider, Thomas ; Schlage, Walter K. ; Ivanov, Nikolai V. ; Peitsch, Manuel C. ; Hoeng, Julia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-857a8ac1fcf5a8b30a800fb838acface65534c0deb19d3f405017bda62107c0e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aerosols</topic><topic>Aging</topic><topic>Aging, Premature - 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Our in vitro study compared, in the context of aging, the effects of the aerosol of Tobacco Heating System 2.2 (THS; an electrically heated tobacco product) and 3R4F reference cigarette smoke (CS) on processes that contribute to vascular pathomechanisms leading to CVD. Young and old human aortic smooth muscle cells (HAoSMC) were exposed to various concentrations of aqueous extracts (AE) from 3R4F CS [0.014–0.22 puffs/mL] or THS aerosol [0.11–1.76 puffs/mL] for 24 h. Key markers were measured by high-content imaging, transcriptomics profiling and multianalyte profiling. In our study, in vitro aging increased senescence, DNA damage, and inflammation and decreased proliferation in the HAoSMCs. At higher concentrations of 3R4F AE, young HAoSMCs behaved similarly to aged cells, while old HAoSMCs showed additional DNA damage and apoptosis effects. At 3R4F AE concentrations with the maximum effect, the THS AE showed no significant effect in young or old HAoSMCs. It required an approximately ten-fold higher concentration of THS AE to induce effects similar to those observed with 3R4F. These effects were independent of nicotine, which did not show a significant effect on HAoSMCs at any tested concentration. Our results show that 3R4F AE accelerates aging in young HAoSMCs and exacerbates the aging effect in old HAoSMCs in vitro, consistent with CS-related contributions to the risk of CVD. Relative to 3R4F AE, the THS AE showed a significantly reduced impact on HAoSMCs, suggesting its lower risk for vascular SMC-associated pathomechanisms leading to CVD.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>34313809</pmid><doi>10.1007/s00204-021-03123-y</doi><tpages>19</tpages><orcidid>https://orcid.org/0000-0001-9729-6853</orcidid><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8448694 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Aerosols Aging Aging, Premature - etiology Aorta Aorta - cytology Aorta - drug effects Apoptosis Apoptosis - drug effects Biomedical and Life Sciences Biomedicine Cardiovascular diseases Cell Proliferation - drug effects Cells, Cultured Cellular Senescence Cigarette smoke Cigarettes Damage Deoxyribonucleic acid DNA DNA damage DNA Damage - drug effects Environmental Health Health risks Humans Inflammation - etiology Muscles Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - pathology Nicotine Occupational Medicine/Industrial Medicine Organ Toxicity and Mechanisms Pharmacology/Toxicology Risk analysis Risk factors Senescence Smoke Smoke - adverse effects Smoking - adverse effects Smooth muscle Tobacco Tobacco Products Toxicology |
| title | Systems toxicology study reveals reduced impact of heated tobacco product aerosol extract relative to cigarette smoke on premature aging and exacerbation effects in aged aortic cells in vitro |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T08%3A50%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Systems%20toxicology%20study%20reveals%20reduced%20impact%20of%20heated%20tobacco%20product%20aerosol%20extract%20relative%20to%20cigarette%20smoke%20on%20premature%20aging%20and%20exacerbation%20effects%20in%20aged%20aortic%20cells%20in%20vitro&rft.jtitle=Archives%20of%20toxicology&rft.au=Poussin,%20Carine&rft.date=2021-10-01&rft.volume=95&rft.issue=10&rft.spage=3341&rft.epage=3359&rft.pages=3341-3359&rft.issn=0340-5761&rft.eissn=1432-0738&rft_id=info:doi/10.1007/s00204-021-03123-y&rft_dat=%3Cproquest_pubme%3E2573636499%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2573636499&rft_id=info:pmid/34313809&rfr_iscdi=true |