Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4640
O. Mcelvaney, D. Fraughen, T. Carroll, M. Herron, M. Casey, L. Alhaddah, E. Reeves, O. Mcelvaney, R. Heeney, M. Murphy, A. Rostron, J. Scott, J. Simpson, N. Mcelvaney
{"title":"Secretion and Retention of Z AAT in Response to SARS-CoV-2 Infection and Similar Stimuli","authors":"O. Mcelvaney, D. Fraughen, T. Carroll, M. Herron, M. Casey, L. Alhaddah, E. Reeves, O. Mcelvaney, R. Heeney, M. Murphy, A. Rostron, J. Scott, J. Simpson, N. Mcelvaney","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4640","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4640","url":null,"abstract":"","PeriodicalId":256335,"journal":{"name":"C65. COPD: PRE-CLINICAL MODELS AND MECHANISMS","volume":"68 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121142292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4628
C. Barrero, F. Wang, M. Rico, M. Florez, B. Kosmider, K. Bahmed, G. Criner
{"title":"Type II Pneumocytes Accumulates Hyperacetylated Histone H3.3 in Smokers and Chronic Obstructive Pulmonary Disease Subjects","authors":"C. Barrero, F. Wang, M. Rico, M. Florez, B. Kosmider, K. Bahmed, G. Criner","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4628","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4628","url":null,"abstract":"","PeriodicalId":256335,"journal":{"name":"C65. COPD: PRE-CLINICAL MODELS AND MECHANISMS","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115834819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4641
D.D. Xing, V. Lin, Y. Wu, G. A. Payne, C. McNicholas, J. M. Wells
Rationale: Angiotensin-converting enzyme 2 (ACE2) is a vasoactive enzyme involved in regulation of vascular tone and blood pressure by reducing angiotensin II and increasing ang(1-7). It is also implicated in the pathogenesis of coronaviruses including SARS-CoV-2. Epidemiological reports differ in implicating cigarette smoking as a risk factor for SARS-CoV-2 infection (COVID-19). Previous studies have been conflicting regarding the implications of cigarette smoke exposure on ACE2 signaling. We hypothesized that cigarette smoke exposure will increase ACE2 expression and impair endothelial cell function. Methods: Female 8-week-old A/J mice were randomly assigned to either air exposure or 48 minutes per day, 5 days per week of cigarette smoke exposure. Mainstream whole-body cigarette smoke exposure was delivered by the SCIREQ “InExpose” smoking system with standard 3R4F research cigarettes. Mouse were sacrificed at 1 and 12 weeks of smoke exposure, and lungs were homogenized and subjected to ACE2 ELISA (Abcam). To investigate the effect of smoking on ACE2 expression and endothelial barrier function, serum starved human pulmonary microvascular endothelial cells (PMVECs) were exposed to cigarette smoke extract (CSE). CSE was prepared at a concentration of 1 cigarette/5 ml in serumfree DMEM and quiescent PMVECs were treated with 1% CSE, 3% CSE or vehicle. Cells were processed for real-time RT-PCR and ELISA 4 hours later, assessment of apoptosis, or underwent TEER to assess endothelial cell barrier function. Results: Lung tissue ACE2 levels were significantly elevated following 1-week of cigarette smoke-exposure. This increase was accompanied by increased macrophage count in bronchoalveolar lavage. Interestingly, at 12-weeks of cigarette smoke-exposure, lung ACE2 was reduced by 15% response. Chronic cigarette smoke-exposure was accompanied by increased right ventricular systolic pressure and Fulton index. In PMVEC models, CSE dose-dependently increased ACE2 mRNA and protein expression. This was accompanied by altered EC barrier function and EC apoptosis. Conclusions: The dose and duration of cigarette smoke exposure affects ACE2 signaling, leading to altered apoptosis and endothelial cell barrier function. These findings have implications for SARS-CoV-2 pathogenesis as well as for furthering our understanding of the effects of smoking on vascular health.
{"title":"Cigarette Smoke Regulates Endothelial ACE2 Expression in the Lung","authors":"D.D. Xing, V. Lin, Y. Wu, G. A. Payne, C. McNicholas, J. M. Wells","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4641","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4641","url":null,"abstract":"Rationale: Angiotensin-converting enzyme 2 (ACE2) is a vasoactive enzyme involved in regulation of vascular tone and blood pressure by reducing angiotensin II and increasing ang(1-7). It is also implicated in the pathogenesis of coronaviruses including SARS-CoV-2. Epidemiological reports differ in implicating cigarette smoking as a risk factor for SARS-CoV-2 infection (COVID-19). Previous studies have been conflicting regarding the implications of cigarette smoke exposure on ACE2 signaling. We hypothesized that cigarette smoke exposure will increase ACE2 expression and impair endothelial cell function. Methods: Female 8-week-old A/J mice were randomly assigned to either air exposure or 48 minutes per day, 5 days per week of cigarette smoke exposure. Mainstream whole-body cigarette smoke exposure was delivered by the SCIREQ “InExpose” smoking system with standard 3R4F research cigarettes. Mouse were sacrificed at 1 and 12 weeks of smoke exposure, and lungs were homogenized and subjected to ACE2 ELISA (Abcam). To investigate the effect of smoking on ACE2 expression and endothelial barrier function, serum starved human pulmonary microvascular endothelial cells (PMVECs) were exposed to cigarette smoke extract (CSE). CSE was prepared at a concentration of 1 cigarette/5 ml in serumfree DMEM and quiescent PMVECs were treated with 1% CSE, 3% CSE or vehicle. Cells were processed for real-time RT-PCR and ELISA 4 hours later, assessment of apoptosis, or underwent TEER to assess endothelial cell barrier function. Results: Lung tissue ACE2 levels were significantly elevated following 1-week of cigarette smoke-exposure. This increase was accompanied by increased macrophage count in bronchoalveolar lavage. Interestingly, at 12-weeks of cigarette smoke-exposure, lung ACE2 was reduced by 15% response. Chronic cigarette smoke-exposure was accompanied by increased right ventricular systolic pressure and Fulton index. In PMVEC models, CSE dose-dependently increased ACE2 mRNA and protein expression. This was accompanied by altered EC barrier function and EC apoptosis. Conclusions: The dose and duration of cigarette smoke exposure affects ACE2 signaling, leading to altered apoptosis and endothelial cell barrier function. These findings have implications for SARS-CoV-2 pathogenesis as well as for furthering our understanding of the effects of smoking on vascular health.","PeriodicalId":256335,"journal":{"name":"C65. COPD: PRE-CLINICAL MODELS AND MECHANISMS","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123965582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4651
U. Sajjan
{"title":"COPD Airway Epithelial Cells Show TLR2 Desensitization Due to Reduced IRAK-1 Expression","authors":"U. Sajjan","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4651","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4651","url":null,"abstract":"","PeriodicalId":256335,"journal":{"name":"C65. COPD: PRE-CLINICAL MODELS AND MECHANISMS","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125295517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4643
C. Cottage, H. Bolt, J. Connor, R. Lemaire, S. Hawkins, A. Berlin, A. Migneault
{"title":"Intratracheal Induction of Lung Senescence by Doxorubicin to Evaluate Senolytics","authors":"C. Cottage, H. Bolt, J. Connor, R. Lemaire, S. Hawkins, A. Berlin, A. Migneault","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4643","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4643","url":null,"abstract":"","PeriodicalId":256335,"journal":{"name":"C65. COPD: PRE-CLINICAL MODELS AND MECHANISMS","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134104176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4653
H. Chand, D. Devadoss, M. Manevski, B. Moukette, S. Kawaguchi, M.N. Sapulveda, N. Barupala, H. Unwalla, I. Rahman, G. Borchert, I.-M. Kim
{"title":"MiR-150-5p Modulates Pulmonary Inflammation and Secretory Mucin Expression Associated with Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease","authors":"H. Chand, D. Devadoss, M. Manevski, B. Moukette, S. Kawaguchi, M.N. Sapulveda, N. Barupala, H. Unwalla, I. Rahman, G. Borchert, I.-M. Kim","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4653","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4653","url":null,"abstract":"","PeriodicalId":256335,"journal":{"name":"C65. COPD: PRE-CLINICAL MODELS AND MECHANISMS","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124577962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4645
A. Bosacoma Armora, Y. Roger, Vea, I. Blanco, O. Tura-Ceide, J. Barberà, V. Peinado
{"title":"Soluble Guanylate Cyclase Stimulators Reverse In Vitro the Effects of Cigarette Smoke Through Normalization of the c-Jun N-Terminal Kinase (JNK) Pathway in Pulmonary Artery Smooth Muscle Cells","authors":"A. Bosacoma Armora, Y. Roger, Vea, I. Blanco, O. Tura-Ceide, J. Barberà, V. Peinado","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4645","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4645","url":null,"abstract":"","PeriodicalId":256335,"journal":{"name":"C65. COPD: PRE-CLINICAL MODELS AND MECHANISMS","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132382173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4642
O. Ukponmwan, A. Dabo, P. Geraghty, R. Foronjy
we the PP2R2C if is critical for the activity of and its influence on Methods: PPP2R2C expression levels were quantified in human small airway epithelial (SAE) cells isolated from healthy subjects and COPD subjects, and mice exposed to cigarette smoke. SAE cells were transfected with PPP2R2C siRNA and were treated with 5% cigarette smoke extract (CSE). Protein and RNA levels of genes of interest were quantified to investigate effect of PPP2R2C expression on cytokine secretion, caspase-3 activity and MAPK activity. Results: Expression of PPP2R2C is decreased in CSE treated cells, and SAE cells isolated from COPD compared to cells from healthy subjects. MMP1, IL-6 and IL-1β expressions increased in CSE exposed cells Silencing 2C increased basal IL-1β protein levels and caused trend increases in other cytokines. Loss of PPP2R2C increased MAPK, NF-κB, and JNK activities. Conclusions of the study: These data demonstrate that reduced expression of PPP2R2C is observed in SAE cells from COPD
{"title":"Suppression of the Protein Phosphatase 2A 2C B Subunit (PPP2R2C) Enhances Immune Responses in Human Bronchiole Small Airway Epithelial Cells","authors":"O. Ukponmwan, A. Dabo, P. Geraghty, R. Foronjy","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4642","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4642","url":null,"abstract":"we the PP2R2C if is critical for the activity of and its influence on Methods: PPP2R2C expression levels were quantified in human small airway epithelial (SAE) cells isolated from healthy subjects and COPD subjects, and mice exposed to cigarette smoke. SAE cells were transfected with PPP2R2C siRNA and were treated with 5% cigarette smoke extract (CSE). Protein and RNA levels of genes of interest were quantified to investigate effect of PPP2R2C expression on cytokine secretion, caspase-3 activity and MAPK activity. Results: Expression of PPP2R2C is decreased in CSE treated cells, and SAE cells isolated from COPD compared to cells from healthy subjects. MMP1, IL-6 and IL-1β expressions increased in CSE exposed cells Silencing 2C increased basal IL-1β protein levels and caused trend increases in other cytokines. Loss of PPP2R2C increased MAPK, NF-κB, and JNK activities. Conclusions of the study: These data demonstrate that reduced expression of PPP2R2C is observed in SAE cells from COPD","PeriodicalId":256335,"journal":{"name":"C65. COPD: PRE-CLINICAL MODELS AND MECHANISMS","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132688807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4621
A. Ito, M. Hashimoto, J. Tanihata, S. Matsubayashi, R. Sasaki, S. Fujimoto, H. Kawamoto, N. Watanabe, T. Kadota, Y. Fujita, S. Ito, D. Takekoshi, S. Minagawa, T. Numata, H. Hara, J. Araya, M. Saito, K. Kuwano
{"title":"Involvement of Parkin-Mediated Mitophagy in the Pathogenesis of COPD-Related Sarcopenia","authors":"A. Ito, M. Hashimoto, J. Tanihata, S. Matsubayashi, R. Sasaki, S. Fujimoto, H. Kawamoto, N. Watanabe, T. Kadota, Y. Fujita, S. Ito, D. Takekoshi, S. Minagawa, T. Numata, H. Hara, J. Araya, M. Saito, K. Kuwano","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4621","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4621","url":null,"abstract":"","PeriodicalId":256335,"journal":{"name":"C65. COPD: PRE-CLINICAL MODELS AND MECHANISMS","volume":"55 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132064369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4620
B. Richmond, C. Marshall, B. Lehmann, V. Polosukhin, T. Blackwell, J. Pietenpol
{"title":"p73 Is Suppressed by Cigarette Smoke and Reduced in the Lungs of Patients with Chronic Obstructive Pulmonary Disease","authors":"B. Richmond, C. Marshall, B. Lehmann, V. Polosukhin, T. Blackwell, J. Pietenpol","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4620","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4620","url":null,"abstract":"","PeriodicalId":256335,"journal":{"name":"C65. COPD: PRE-CLINICAL MODELS AND MECHANISMS","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134493064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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