Jekaterina Aid, Ajime Tom Tanjeko, Jef Serré, Moritz Eggelbusch, Wendy Noort, Gerard M. J. de Wit, Michel van Weeghel, Marju Puurand, Kersti Tepp, Ghislaine Gayan-Ramirez, Hans Degens, Tuuli Käämbre, Rob C. I. Wüst
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We hypothesized that smoking negatively affects cardiac metabolism and induces local inflammation in mice, which do not readily reverse upon 2-week smoking cessation.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Mice were exposed to air or cigarette smoke for 14 weeks with or without 1- or 2-week smoke cessation. We measured cardiac mitochondrial respiration by high-resolution respirometry, cardiac mitochondrial density, abundance of mitochondrial supercomplexes by electrophoresis, and capillarization, fibrosis, and macrophage infiltration by immunohistology, and performed cardiac metabolome and lipidome analysis by mass spectrometry.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Mitochondrial protein, supercomplex content, and respiration (all <i>p</i> < 0.03) were lower after smoking, which were largely reversed within 2-week smoking cessation. Metabolome and lipidome analyses revealed alterations in mitochondrial metabolism, a shift from fatty acid to glucose metabolism, which did not revert to control upon smoking cessation. Capillary density was not different after smoking but increased after smoking cessation (<i>p</i> = 0.02). Macrophage infiltration and fibrosis (<i>p</i> < 0.04) were higher after smoking but did not revert to control upon smoking cessation.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>While cigarette-impaired smoking-induced cardiac mitochondrial function was reversed by smoking cessation, the remaining fibrosis and macrophage infiltration may contribute to the increased risk of cardiovascular events after smoking cessation.</p>\n </section>\n </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":5.6000,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14145","citationCount":"0","resultStr":"{\"title\":\"Smoking cessation only partially reverses cardiac metabolic and structural remodeling in mice\",\"authors\":\"Jekaterina Aid, Ajime Tom Tanjeko, Jef Serré, Moritz Eggelbusch, Wendy Noort, Gerard M. 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引用次数: 0
摘要
目的主动吸烟是慢性阻塞性肺病的一个主要危险因素,戒烟后吸烟率仍会升高。吸烟后骨骼肌功能障碍已得到充分证实,但人们对心脏对吸烟的适应性却知之甚少。独立于生活方式因素的潜在细胞和分子心脏适应性以及戒烟后可逆性的时间过程仍不清楚。我们假设吸烟会对小鼠的心脏新陈代谢产生负面影响并诱发局部炎症,而戒烟 2 周后这些影响并不会轻易逆转。我们用高分辨率呼吸测定法测量了心脏线粒体呼吸,用电泳法测定了心脏线粒体密度、线粒体超级复合物丰度,用免疫组织学方法测量了毛细血管化、纤维化和巨噬细胞浸润,并用质谱法进行了心脏代谢组和脂质组分析。结果吸烟后线粒体蛋白、超级复合物含量和呼吸量降低(均 p < 0.03),但在戒烟两周内基本逆转。代谢组和脂质组分析显示线粒体代谢发生了改变,从脂肪酸代谢转向葡萄糖代谢,但戒烟后并未恢复到控制水平。毛细血管密度在吸烟后没有变化,但在戒烟后有所增加(p = 0.02)。结论虽然戒烟可逆转吸烟导致的心脏线粒体功能受损,但残留的纤维化和巨噬细胞浸润可能是戒烟后心血管事件风险增加的原因。
Smoking cessation only partially reverses cardiac metabolic and structural remodeling in mice
Aims
Active cigarette smoking is a major risk factor for chronic obstructive pulmonary disease that remains elevated after cessation. Skeletal muscle dysfunction has been well documented after smoking, but little is known about cardiac adaptations to cigarette smoking. The underlying cellular and molecular cardiac adaptations, independent of confounding lifestyle factors, and time course of reversibility by smoking cessation remain unclear. We hypothesized that smoking negatively affects cardiac metabolism and induces local inflammation in mice, which do not readily reverse upon 2-week smoking cessation.
Methods
Mice were exposed to air or cigarette smoke for 14 weeks with or without 1- or 2-week smoke cessation. We measured cardiac mitochondrial respiration by high-resolution respirometry, cardiac mitochondrial density, abundance of mitochondrial supercomplexes by electrophoresis, and capillarization, fibrosis, and macrophage infiltration by immunohistology, and performed cardiac metabolome and lipidome analysis by mass spectrometry.
Results
Mitochondrial protein, supercomplex content, and respiration (all p < 0.03) were lower after smoking, which were largely reversed within 2-week smoking cessation. Metabolome and lipidome analyses revealed alterations in mitochondrial metabolism, a shift from fatty acid to glucose metabolism, which did not revert to control upon smoking cessation. Capillary density was not different after smoking but increased after smoking cessation (p = 0.02). Macrophage infiltration and fibrosis (p < 0.04) were higher after smoking but did not revert to control upon smoking cessation.
Conclusions
While cigarette-impaired smoking-induced cardiac mitochondrial function was reversed by smoking cessation, the remaining fibrosis and macrophage infiltration may contribute to the increased risk of cardiovascular events after smoking cessation.
期刊介绍:
Acta Physiologica is an important forum for the publication of high quality original research in physiology and related areas by authors from all over the world. Acta Physiologica is a leading journal in human/translational physiology while promoting all aspects of the science of physiology. The journal publishes full length original articles on important new observations as well as reviews and commentaries.