Caihong Liu , Yanwei Zhang , Jianli Zhao , John Zhang , Zhijun Meng , Yuhui Yang , Yaoli Xie , Xiangying Jiao , Bin Liang , Jimin Cao , Yajing Wang
{"title":"吸烟/电子烟诱导的肺细胞外囊泡通过ERK5的转位加剧了心肌细胞损伤。","authors":"Caihong Liu , Yanwei Zhang , Jianli Zhao , John Zhang , Zhijun Meng , Yuhui Yang , Yaoli Xie , Xiangying Jiao , Bin Liang , Jimin Cao , Yajing Wang","doi":"10.1016/j.lfs.2024.123195","DOIUrl":null,"url":null,"abstract":"<div><h3>Aims</h3><div>The impact of e-cigarettes/vaping on cardiac function remains contradictory owing to insufficient direct evidence of interorgan communication. Extracellular vesicles (EVs) have protective or detrimental effects depending on pathological conditions, making it crucial to understand their role in lung-cardiac cell interactions mediated by vaping inhalation.</div></div><div><h3>Methods and key findings</h3><div>Pulmonary EVs were characterized from animals that underwent 12 weeks of nicotine inhalation (vaping component) (EVs<sup>Nicotine</sup>) or vehicle control (EVs<sup>Vehicle</sup>). EVs<sup>Nicotine</sup> significantly increased in size and abundance compared with EVs<sup>Vehicle</sup>. The direct effect of EVs <sup>Nicotine</sup> and EVs <sup>Vehicle</sup> on cardiomyocytes was then assessed in vitro and in vivo. EVs <sup>Nicotine</sup> led to a decrease in cardiac function as manifested by reduced cardiac contractility and impaired relaxation. EVs <sup>Nicotine</sup> induced increased levels of cleaved caspase-1 and cleaved caspase-11 in cardiomyocytes, indicating the promotion of pyroptosis. Meanwhile, EVs<sup>Nicotine</sup> stimulated the secretion of fibrotic factors. Further analysis revealed that nicotine inhalation stimulated EVs <sup>Nicotine</sup> enriched with high levels of ERK5 (EVs <sup>Nicotine</sup>-ERK5). It was discovered that these EVs derived from pulmonary epithelial cells. Furthermore, inhibiting cardiac ERK5 blunted the EVs <sup>Nicotine</sup>-induced pyroptosis and fibrotic factor secretion. We further identified GATA4, a pro-pyroptosis transcription factor, as being activated through ERK5-dependent phosphorylation.</div></div><div><h3>Significance</h3><div>Our research demonstrates that nicotine inhalation exacerbates cardiac injury through the activation of EVs derived from the lungs during e-cigarettes/vaping. Specifically, the EVs containing ERK5 play a crucial role in mediating the detrimental effects on cardiac function. This research provides new insights into the cardiac toxicity of vaping and highlights the role of EVs <sup>Nicotine</sup>-ERK5 in this process.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123195"},"PeriodicalIF":5.2000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Vaping/e-cigarette-induced pulmonary extracellular vesicles contribute to exacerbated cardiomyocyte impairment through the translocation of ERK5\",\"authors\":\"Caihong Liu , Yanwei Zhang , Jianli Zhao , John Zhang , Zhijun Meng , Yuhui Yang , Yaoli Xie , Xiangying Jiao , Bin Liang , Jimin Cao , Yajing Wang\",\"doi\":\"10.1016/j.lfs.2024.123195\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Aims</h3><div>The impact of e-cigarettes/vaping on cardiac function remains contradictory owing to insufficient direct evidence of interorgan communication. Extracellular vesicles (EVs) have protective or detrimental effects depending on pathological conditions, making it crucial to understand their role in lung-cardiac cell interactions mediated by vaping inhalation.</div></div><div><h3>Methods and key findings</h3><div>Pulmonary EVs were characterized from animals that underwent 12 weeks of nicotine inhalation (vaping component) (EVs<sup>Nicotine</sup>) or vehicle control (EVs<sup>Vehicle</sup>). EVs<sup>Nicotine</sup> significantly increased in size and abundance compared with EVs<sup>Vehicle</sup>. The direct effect of EVs <sup>Nicotine</sup> and EVs <sup>Vehicle</sup> on cardiomyocytes was then assessed in vitro and in vivo. EVs <sup>Nicotine</sup> led to a decrease in cardiac function as manifested by reduced cardiac contractility and impaired relaxation. EVs <sup>Nicotine</sup> induced increased levels of cleaved caspase-1 and cleaved caspase-11 in cardiomyocytes, indicating the promotion of pyroptosis. Meanwhile, EVs<sup>Nicotine</sup> stimulated the secretion of fibrotic factors. Further analysis revealed that nicotine inhalation stimulated EVs <sup>Nicotine</sup> enriched with high levels of ERK5 (EVs <sup>Nicotine</sup>-ERK5). It was discovered that these EVs derived from pulmonary epithelial cells. Furthermore, inhibiting cardiac ERK5 blunted the EVs <sup>Nicotine</sup>-induced pyroptosis and fibrotic factor secretion. We further identified GATA4, a pro-pyroptosis transcription factor, as being activated through ERK5-dependent phosphorylation.</div></div><div><h3>Significance</h3><div>Our research demonstrates that nicotine inhalation exacerbates cardiac injury through the activation of EVs derived from the lungs during e-cigarettes/vaping. Specifically, the EVs containing ERK5 play a crucial role in mediating the detrimental effects on cardiac function. This research provides new insights into the cardiac toxicity of vaping and highlights the role of EVs <sup>Nicotine</sup>-ERK5 in this process.</div></div>\",\"PeriodicalId\":18122,\"journal\":{\"name\":\"Life sciences\",\"volume\":\"358 \",\"pages\":\"Article 123195\"},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2024-10-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Life sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0024320524007859\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0024320524007859","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Vaping/e-cigarette-induced pulmonary extracellular vesicles contribute to exacerbated cardiomyocyte impairment through the translocation of ERK5
Aims
The impact of e-cigarettes/vaping on cardiac function remains contradictory owing to insufficient direct evidence of interorgan communication. Extracellular vesicles (EVs) have protective or detrimental effects depending on pathological conditions, making it crucial to understand their role in lung-cardiac cell interactions mediated by vaping inhalation.
Methods and key findings
Pulmonary EVs were characterized from animals that underwent 12 weeks of nicotine inhalation (vaping component) (EVsNicotine) or vehicle control (EVsVehicle). EVsNicotine significantly increased in size and abundance compared with EVsVehicle. The direct effect of EVs Nicotine and EVs Vehicle on cardiomyocytes was then assessed in vitro and in vivo. EVs Nicotine led to a decrease in cardiac function as manifested by reduced cardiac contractility and impaired relaxation. EVs Nicotine induced increased levels of cleaved caspase-1 and cleaved caspase-11 in cardiomyocytes, indicating the promotion of pyroptosis. Meanwhile, EVsNicotine stimulated the secretion of fibrotic factors. Further analysis revealed that nicotine inhalation stimulated EVs Nicotine enriched with high levels of ERK5 (EVs Nicotine-ERK5). It was discovered that these EVs derived from pulmonary epithelial cells. Furthermore, inhibiting cardiac ERK5 blunted the EVs Nicotine-induced pyroptosis and fibrotic factor secretion. We further identified GATA4, a pro-pyroptosis transcription factor, as being activated through ERK5-dependent phosphorylation.
Significance
Our research demonstrates that nicotine inhalation exacerbates cardiac injury through the activation of EVs derived from the lungs during e-cigarettes/vaping. Specifically, the EVs containing ERK5 play a crucial role in mediating the detrimental effects on cardiac function. This research provides new insights into the cardiac toxicity of vaping and highlights the role of EVs Nicotine-ERK5 in this process.
期刊介绍：
Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed.
The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.
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