Studying the relationship between allergo-inflammation and left atrium and pulmonary vein pathological changes in allergic asthma
Main Article Content
Keywords
remodeling, heart, lung, inflammation, cytokine
Abstract
Allergic asthma is an inflammatory airway disease influenced by genetic and environmental factors and orchestrated by imbalance between T helper 1 cell (Th1) and two immune responses. Inflammation contributes to pathological changes and remodeling in tissues such as the vascular, lung, heart, and beds. The purpose for this study was to evaluate the effects of allergic asthma on heart pathology and remodeling. In methodology, mice were allocated into two healthy and asthma groups, followed by the assessment of airway hyperresponsiveness (AHR), cell enumeration in bronchoalveolar lavage fluid (BALF), measurement of interleukin (IL)-4, IL-33, IL-5, interferon gamma (IFN-γ), and IL-13, total immunoglobulin E (IgE) levels, and analysis of remodeling factors. Also, gene expression analysis was performed for troponin, suppressor of mothers against decapentaplegic (SMAD)2, myocyte enhancer factor 2 (MEF-2), and SMAD3. Finally, histopathological study was conducted. The result revealed that asthma induction augmented AHR and elevated eosinophil percentage, elevated the levels of IL-13, IL-33, IL-5, IL-4, IgE, Helicobacter pylori (HP), and transforming growth factor beta (TGF-β), and the gene expression of SMAD3. Also, eosinophilic inflammation, goblet cell meta/hyperplasia, and mucus secretion were increased in asthmatic versus healthy mice. The level of IFN-γ was lower in the asthma compared to the control group; however, the expressions of troponin, SMAD2, and MEF-2 genes showed no significant differences. It was concluded that allergic asthma changed the balance between type 1 and 2 cytokines, which could possibly lead to profound effects on the cardiovascular system’s structure and/or function.
References
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2 Bagheri Lankarani K, Honarvar B, Athari SS. The mechanisms underlying helicobacter pylori-mediated protection against allergic asthma. Tanaffos. 2017;16(4):251–9.
3 Athari SM, Mehrabi Nasab E, Athari SS. Study effect of Ocimum basilicum seeds on mucus production and cytokine gene expression in allergic asthma mice model. Rev Fr Allergol. 2018;58(7):489–93.
4 Minmin HE, Mehrabi Nasab E, Athari SS. Immunoregulatory effect of mesenchymal stem cell via mitochondria signaling pathways in allergic asthma. Saudi J Biol Sci. 2021;28:6957–62. 10.1016/j.sjbs.2021.07.071
5 Mehrabi Nasab E, Athari SM, Motlagh B, Athari SS Effects of oral administration of Ocimum basilicum on goblet cell hyperplasia and upstream cytokine gene expression in allergic asthma. Rev Fr Allergol. 2020;. 60:64–8.
6 Jiang J, Mehrabi Nasab E, Athari SM, Athari SS. Effects of vitamin E and selenium on allergic rhinitis and asthma pathophysiology. Respir Physiol Neurobiol. 2021;286:103614. 10.1016/j.resp.2020.103614
7 Esmaeilzadeh A, Tahmasebi S, Athari SS. Chimeric antigen receptor T cell therapy: Applications and challenges in treatment of allergy and asthma. Biomed Pharmacother. 2020;123:109685. 10.1016/j.biopha.2019.109685
8 Hajimohammadi B, Athari SM, Abdollahi M, Vahedi G, Athari SS. Oral administration of acrylamide worsens the inflammatory responses in the airways of asthmatic mice through agitation of oxidative stress in the lungs. Front Immunol. 2020;11:1940. 10.3389/fimmu.2020.01940
9 Hoit BD. Evaluation of left atrial function: Current status. Struct Heart. 2017;1:(3–4):109–20. 10.1080/24748706.2017.1353718
10 To AC, Flamm SD, Marwick TH, Klein AL. Clinical utility of multimodality LA imaging: Assessment of size, function, and structure. JACC. 2011;4:788–98. 10.1016/j.jcmg.2011.02.018
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12 Pandey NN, Taxak A, Kumar S. Normal pulmonary venous anatomy and non-anomalous variations demonstrated on CT angiography: What the radiologist needs to know? Br J Radiol. 2020;93:20200595. 10.1259/bjr.20200595
13 Athari SS, Athari SM. The importance of eosinophil, platelet and dendritic cell in asthma. Asian Pac J Trop Dis. 2014;4(1):S41–7. 10.1016/S2222-1808(14)60413-8
14 Zhou Y, Li L, Yu Z, Gu X, Pan R, Li Q , et al. Dermatophagoides pteronyssinus allergen Der p 22: Cloning, expression, IgE-binding in asthmatic children, and immunogenicity. Pediatr Allergy Immunol. 2022; 33(8):e13835.
15 Wang H, Li B, Sun Y, Ma Q, Feng Y, Jia Y, et al. NIR-II AIE Luminogen-Based Erythrocyte-Like Nanoparticles with Granuloma-Targeting and Self-Oxygenation Characteristics for Combined Phototherapy of Tuberculosis. Adv Mater. 2024; 36(38):e2406143.
16 Luo J, Li X, Zhang L, Deng M, Zhao J, Zhang J, et al. 5-deoxy-rutaecarpine protects against LPS-induced acute lung injury via inhibiting NLRP3 inflammasome-related inflammation. Front Pharmacol. 2025; 16:1522146.
17 Athari SS. Targeting cell signaling in allergic asthma. Signal Transduct Target Ther. 2019;4:45. 10.1038/s41392-019-0079-0
18 Buckner K. Cardiac asthma. Immunol Allergy Clin N Am. 2013;33:35–44. 10.1016/j.iac.2012.10.012
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24 Tattersall MC, Dasiewicz AS, McClelland RL, Gepner AD, Kalscheur MM, Field ME, et al. Persistent asthma is associated with increased risk for incident atrial fibrillation in the MESA. Circ Arrhythm Electrophysiol. 2020;13(2):e007685. 10.1161/CIRCEP.119.007685
25 Lip GY, Rumley A, Dunn FG, Lowe GD. Plasma fibrinogen and fibrin D-dimer in patients with atrial fibrillation: Effects of cardioversion to sinus rhythm. Int J Cardiol. 1995;51:245–51. 10.1016/0167-5273(95)02434-x
26 Yalcin AD, Celik B, Gumuslu S. D-dimer levels decreased in severe allergic asthma and chronic urticaria patients with the omalizumab treatment. Expert Opin Biol Ther. 2014; 14:283–6. 10.1517/14712598.2014.875525.
27 de Boer JD, Majoor CJ, van’t Veer C, Bel EH, van der Poll T. Asthma and coagulation. Blood. 2012;119:3236–44. 10.1182/blood-2011-11-391532
28 Lowe GD, Rumley A, McMahon AD, Ford I, O’Reilly DS, Packard CJ. Interleukin-6, fibrin D-dimer, and coagulation factors VII and XIIa in prediction of coronary heart disease. Arterioscler Thromb Vasc Biol. 2004;24:1529–34. 10.1161/01.ATV.0000135995.39488.6c
29 Cepelis C, Brumpton BM, Malmo V, Laugsand LE, Loennechen JP, Ellekjar H, et al. Associations of asthma and asthma control with atrial fibrillation risk results from the Nord-Trondelag Health Study (HUNT). JAMA. 10.1001/jamacardio.2018.1901
30 Menezes AR, Lavie CJ, DiNicolantonio JJ, O’Keefe J, Morin DP, Khatib S, Milani RV.. Atrial fibrillation in the 21st century: a current understanding of risk factors and primary prevention strategies. Mayo Clin Proc. 2013;88(4):394–409. 10.1016/j.mayocp.2013.01.022
31 Li J, Solus J, Chen Q, Rho YH, Milne G, C Michael Stein CM, et al. Role of inflammation and oxidative stress in atrial fibrillation. Heart Rhythm. 2010;7(4):438–44. 10.1016/j.hrthm.2009.12.009
32 Avdalovic M. Pulmonary vasculature and critical asthma syndromes: A comprehensive review. Clinic Rev Allerg Immunol. 2015;48:97–103. 10.1007/s12016-014-8420-4
33 Folmsbee SS, Budinger GRS, Bryce PJ, Gottardi CJ. The cardiomyocyte protein alpha-T-catenin contributes to asthma through regulating pulmonary vein inflammation. J Allergy Clin Immunol. 2016;138(1):123–9.e2. 10.1016/j.jaci.2015.11.037
34 Ma K, Li C, Xu J, Ren F, Xu X, Liu C, et al. LncRNA Gm16410 regulates PM2.5-induced lung endothelial-mesenchymal transition via the TGF-β1/Smad3/p-Smad3 pathway. Ecotoxicol Environ Saf. 2020;205:111327. 10.1016/j.ecoenv.2020.111327
35 Zhou Y, Duan Q, Yang D. In vitro human cell-based models to study airway remodeling in asthma. Biomed Pharmacother. 2023;159:114218. 10.1016/j.biopha.2023.114218
36 Bernard DJ. Both SMAD2 and SMAD3 mediate activin-stimulated expression of the follicle-stimulating hormone–Subunit in mouse gonadotrope cells. Mol Endocrinol. 2004;18(3):606–23. 10.1210/me.2003-0264
37 Sun B, Wu H, Lu J, Zhang R, Shen X, Gu Y, et al. Irisin reduces bone fracture by facilitating osteogenesis and antagonizing TGF-β/Smad signaling in a growing mouse model of osteogenesis imperfecta. J Orthop Translat. 2023;38:175–89. 10.1016/j.jot.2022.10.012
38 Watanabe R, Yamada Y, Ihara Y, Someya Y, Kubota A, Kagimoto S, et al. The MH1 domains of Smad2 and Smad3 are involved in the regulation of the ALK7 signals. Biochem Biophys Res Commun. 1999;254:707–12. 10.1006/bbrc.1998.0118
39 Umezu T, Nakamura S, Sato Y, Kobayashi T, Ito E, Abe T, et al. Smad2 and Smad3 expressed in skeletal muscle promote immobilization-induced bone atrophy in mice. Biochem Biophys Res Commun. 2021;582:111e117. 10.1016/j.bbrc.2021.10.043
40 Moir LM, Burgess JK, Black JL. Transforming growth factor beta 1 increases fibronectin deposition through integrin receptor alpha 5 beta 1 on human airway smooth muscle. J Allergy Clin Immunol. 2008;121:1034–39. 10.1016/j.jaci.2007.12.1159
41 Waseem AM, Kim M-S, Adachi M, Morris MJ, Qi X, Richardson JA, et al. In vivo analysis of MEF2 transcription factors in synapse regulation and neuronal survival. PLoS ONE. 2012;7(4):e34863. 10.1371/journal.pone.0034863
42 Jain P, Lavorgna A, Sehgal M, Gao L, Ginwala R, Sagar D, et al. Myocyte enhancer factor (MEF)-2 plays essential roles in T-cell transformation associated with HTLV-1 infection by stabilizing complex between tax and CREB. Retrovirology. 2015;12:23. 10.1186/s12977-015-0140-1
43 Lu J, McKinsey TA, Zhang C-L, Olson EN. Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases. Mol Cell. 2000;6:233–44. 10.1016/s1097-2765(00)00025-3
44 Jung C-C, Su H-J. Long-term allergen exposure induces adipose tissue inflammation and circulatory system injury. Cellular Immunol. 2016;303:34–42. 10.1016/j.cellimm.2016.03.002
45 Xue Z, Guo S, Liu X, Ma J, Zhu W, Zhou Y, et al. Impact of COPD or asthma on the risk of atrial fibrillation: A systematic review and meta-analysis. Front Cardiovasc Med. 2022;9:872446. 10.3389/fcvm.2022.872446
46 Goudis CA. Chronic obstructive pulmonary disease and atrial fibrillation: An unknown relationship. J Cardiol. 2017;69:699–705. 10.1016/j.jjcc.2016.12.013
47 Ganga HV, Nair SU, Puppala VK, Miller WL. Risk of newonset atrial fibrillation in elderly patients with the overlap syndrome: A retrospective cohort study. J Geriatr Cardiol. 2013;10:129–34. 10.3969/j.issn.1671-5411.2013.02.001
48 Yang X, Zhang L, Liu H, Shao Y, Zhang S. Cardiac sympathetic denervation suppresses atrial fibrillation and blood pressure in a chronic intermittent hypoxia rat model of obstructive sleep apnea. J Am Heart Assoc. 2019;8:e010254. 10.1161/JAHA.118.010254
49 Kang H, Bae BS, Kim JH, Jang HS, Lee BR, Jung BC. The relationship between chronic atrial fibrillation and reduced pulmonary function in cases of preserved left ventricular systolic function. Korean Circ J. 2009;39:372–7. 10.4070/kcj.2009.39.9.372
50 Simons SO, Elliott A, Sastry M, Hendriks JM, Arzt M, Rienstra M, et al. Chronic obstructive pulmonary disease and atrial fibrillation: An interdisciplinary perspective. Eur Heart J. 2021;42:532–40. 10.1093/eurheartj/ehaa822
51 R. Khan. Identifying and understanding the role of pulmonary vein activity in atrial fibrillation. Cardiovasc Res. 2004;64(3):387–94. 10.1016/j.cardiores.2004.07.025
52 Liu M, Chen R, Zheng Z, Xu S, Hou C, Ding Y, et al. Mechanisms of inflammatory microenvironment formation in cardiometabolic diseases: molecular and cellular perspectives. Front Cardiovasc Med. 2025; 11:1529903.
53 Liu T, Zeng J, Zhao X, Fu R, Peng L, Li X, et al. Relationship between vascular aging and left ventricular geometry in patients with obstructive sleep apnea hypopnea syndrome-related hypertension. Sci Rep. 2025; 15:6191
54 Edriss H, Denega T, Test V, Nugent K. Pulmonary vein stenosis complicating radiofrequency catheter ablation for atrial fibrillation: A literature review. Respir Med. 2016;117:215–22. 10.1016/j.rmed.2016.06.014
2 Bagheri Lankarani K, Honarvar B, Athari SS. The mechanisms underlying helicobacter pylori-mediated protection against allergic asthma. Tanaffos. 2017;16(4):251–9.
3 Athari SM, Mehrabi Nasab E, Athari SS. Study effect of Ocimum basilicum seeds on mucus production and cytokine gene expression in allergic asthma mice model. Rev Fr Allergol. 2018;58(7):489–93.
4 Minmin HE, Mehrabi Nasab E, Athari SS. Immunoregulatory effect of mesenchymal stem cell via mitochondria signaling pathways in allergic asthma. Saudi J Biol Sci. 2021;28:6957–62. 10.1016/j.sjbs.2021.07.071
5 Mehrabi Nasab E, Athari SM, Motlagh B, Athari SS Effects of oral administration of Ocimum basilicum on goblet cell hyperplasia and upstream cytokine gene expression in allergic asthma. Rev Fr Allergol. 2020;. 60:64–8.
6 Jiang J, Mehrabi Nasab E, Athari SM, Athari SS. Effects of vitamin E and selenium on allergic rhinitis and asthma pathophysiology. Respir Physiol Neurobiol. 2021;286:103614. 10.1016/j.resp.2020.103614
7 Esmaeilzadeh A, Tahmasebi S, Athari SS. Chimeric antigen receptor T cell therapy: Applications and challenges in treatment of allergy and asthma. Biomed Pharmacother. 2020;123:109685. 10.1016/j.biopha.2019.109685
8 Hajimohammadi B, Athari SM, Abdollahi M, Vahedi G, Athari SS. Oral administration of acrylamide worsens the inflammatory responses in the airways of asthmatic mice through agitation of oxidative stress in the lungs. Front Immunol. 2020;11:1940. 10.3389/fimmu.2020.01940
9 Hoit BD. Evaluation of left atrial function: Current status. Struct Heart. 2017;1:(3–4):109–20. 10.1080/24748706.2017.1353718
10 To AC, Flamm SD, Marwick TH, Klein AL. Clinical utility of multimodality LA imaging: Assessment of size, function, and structure. JACC. 2011;4:788–98. 10.1016/j.jcmg.2011.02.018
11 Simard T, Sarma D, Miranda WR, Jain CC, Anderson JH, Collins JD, et al. Pathogenesis, evaluation, and management of pulmonary vein stenosis. JACC. 2023;81(24):2361–73. 10.1016/j.jacc.2023.04.016
12 Pandey NN, Taxak A, Kumar S. Normal pulmonary venous anatomy and non-anomalous variations demonstrated on CT angiography: What the radiologist needs to know? Br J Radiol. 2020;93:20200595. 10.1259/bjr.20200595
13 Athari SS, Athari SM. The importance of eosinophil, platelet and dendritic cell in asthma. Asian Pac J Trop Dis. 2014;4(1):S41–7. 10.1016/S2222-1808(14)60413-8
14 Zhou Y, Li L, Yu Z, Gu X, Pan R, Li Q , et al. Dermatophagoides pteronyssinus allergen Der p 22: Cloning, expression, IgE-binding in asthmatic children, and immunogenicity. Pediatr Allergy Immunol. 2022; 33(8):e13835.
15 Wang H, Li B, Sun Y, Ma Q, Feng Y, Jia Y, et al. NIR-II AIE Luminogen-Based Erythrocyte-Like Nanoparticles with Granuloma-Targeting and Self-Oxygenation Characteristics for Combined Phototherapy of Tuberculosis. Adv Mater. 2024; 36(38):e2406143.
16 Luo J, Li X, Zhang L, Deng M, Zhao J, Zhang J, et al. 5-deoxy-rutaecarpine protects against LPS-induced acute lung injury via inhibiting NLRP3 inflammasome-related inflammation. Front Pharmacol. 2025; 16:1522146.
17 Athari SS. Targeting cell signaling in allergic asthma. Signal Transduct Target Ther. 2019;4:45. 10.1038/s41392-019-0079-0
18 Buckner K. Cardiac asthma. Immunol Allergy Clin N Am. 2013;33:35–44. 10.1016/j.iac.2012.10.012
19 Ware LB, Matthay MA. Clinical practice: Acute pulmonary edema. N Engl J Med. 2005;353:2788. 10.1056/NEJMcp052699
20 Gehlbach BK, Geppert E. The pulmonary manifestations of left heart failure. Chest. 2004;125(2):669–82. 10.1378/chest.125.2.669
21 Matthay MA, Martin TR. Pulmonary edema and acute lung injury. In: Murray JF, Nadel JA, Mason RJ, et al., editors. Textbook of respiratory medicine. 5th edition. Philadelphia: WB Saunders Company; 2010, pp. 1283–355.
22 Dimopoulou I, Daganou M, Tsintzas OK, Tzelepis GE. Effects of severity of long-standing congestive heart failure on pulmonary function. Respir Med. 1998;92:1321–5. 10.1016/s0954-6111(98)90136-6
23 Mann DL, Bristow MR. Mechanisms and models in heart failure: The biomechanical and beyond. Circulation. 2005;111:2837. 10.1161/CIRCULATIONAHA.104.500546
24 Tattersall MC, Dasiewicz AS, McClelland RL, Gepner AD, Kalscheur MM, Field ME, et al. Persistent asthma is associated with increased risk for incident atrial fibrillation in the MESA. Circ Arrhythm Electrophysiol. 2020;13(2):e007685. 10.1161/CIRCEP.119.007685
25 Lip GY, Rumley A, Dunn FG, Lowe GD. Plasma fibrinogen and fibrin D-dimer in patients with atrial fibrillation: Effects of cardioversion to sinus rhythm. Int J Cardiol. 1995;51:245–51. 10.1016/0167-5273(95)02434-x
26 Yalcin AD, Celik B, Gumuslu S. D-dimer levels decreased in severe allergic asthma and chronic urticaria patients with the omalizumab treatment. Expert Opin Biol Ther. 2014; 14:283–6. 10.1517/14712598.2014.875525.
27 de Boer JD, Majoor CJ, van’t Veer C, Bel EH, van der Poll T. Asthma and coagulation. Blood. 2012;119:3236–44. 10.1182/blood-2011-11-391532
28 Lowe GD, Rumley A, McMahon AD, Ford I, O’Reilly DS, Packard CJ. Interleukin-6, fibrin D-dimer, and coagulation factors VII and XIIa in prediction of coronary heart disease. Arterioscler Thromb Vasc Biol. 2004;24:1529–34. 10.1161/01.ATV.0000135995.39488.6c
29 Cepelis C, Brumpton BM, Malmo V, Laugsand LE, Loennechen JP, Ellekjar H, et al. Associations of asthma and asthma control with atrial fibrillation risk results from the Nord-Trondelag Health Study (HUNT). JAMA. 10.1001/jamacardio.2018.1901
30 Menezes AR, Lavie CJ, DiNicolantonio JJ, O’Keefe J, Morin DP, Khatib S, Milani RV.. Atrial fibrillation in the 21st century: a current understanding of risk factors and primary prevention strategies. Mayo Clin Proc. 2013;88(4):394–409. 10.1016/j.mayocp.2013.01.022
31 Li J, Solus J, Chen Q, Rho YH, Milne G, C Michael Stein CM, et al. Role of inflammation and oxidative stress in atrial fibrillation. Heart Rhythm. 2010;7(4):438–44. 10.1016/j.hrthm.2009.12.009
32 Avdalovic M. Pulmonary vasculature and critical asthma syndromes: A comprehensive review. Clinic Rev Allerg Immunol. 2015;48:97–103. 10.1007/s12016-014-8420-4
33 Folmsbee SS, Budinger GRS, Bryce PJ, Gottardi CJ. The cardiomyocyte protein alpha-T-catenin contributes to asthma through regulating pulmonary vein inflammation. J Allergy Clin Immunol. 2016;138(1):123–9.e2. 10.1016/j.jaci.2015.11.037
34 Ma K, Li C, Xu J, Ren F, Xu X, Liu C, et al. LncRNA Gm16410 regulates PM2.5-induced lung endothelial-mesenchymal transition via the TGF-β1/Smad3/p-Smad3 pathway. Ecotoxicol Environ Saf. 2020;205:111327. 10.1016/j.ecoenv.2020.111327
35 Zhou Y, Duan Q, Yang D. In vitro human cell-based models to study airway remodeling in asthma. Biomed Pharmacother. 2023;159:114218. 10.1016/j.biopha.2023.114218
36 Bernard DJ. Both SMAD2 and SMAD3 mediate activin-stimulated expression of the follicle-stimulating hormone–Subunit in mouse gonadotrope cells. Mol Endocrinol. 2004;18(3):606–23. 10.1210/me.2003-0264
37 Sun B, Wu H, Lu J, Zhang R, Shen X, Gu Y, et al. Irisin reduces bone fracture by facilitating osteogenesis and antagonizing TGF-β/Smad signaling in a growing mouse model of osteogenesis imperfecta. J Orthop Translat. 2023;38:175–89. 10.1016/j.jot.2022.10.012
38 Watanabe R, Yamada Y, Ihara Y, Someya Y, Kubota A, Kagimoto S, et al. The MH1 domains of Smad2 and Smad3 are involved in the regulation of the ALK7 signals. Biochem Biophys Res Commun. 1999;254:707–12. 10.1006/bbrc.1998.0118
39 Umezu T, Nakamura S, Sato Y, Kobayashi T, Ito E, Abe T, et al. Smad2 and Smad3 expressed in skeletal muscle promote immobilization-induced bone atrophy in mice. Biochem Biophys Res Commun. 2021;582:111e117. 10.1016/j.bbrc.2021.10.043
40 Moir LM, Burgess JK, Black JL. Transforming growth factor beta 1 increases fibronectin deposition through integrin receptor alpha 5 beta 1 on human airway smooth muscle. J Allergy Clin Immunol. 2008;121:1034–39. 10.1016/j.jaci.2007.12.1159
41 Waseem AM, Kim M-S, Adachi M, Morris MJ, Qi X, Richardson JA, et al. In vivo analysis of MEF2 transcription factors in synapse regulation and neuronal survival. PLoS ONE. 2012;7(4):e34863. 10.1371/journal.pone.0034863
42 Jain P, Lavorgna A, Sehgal M, Gao L, Ginwala R, Sagar D, et al. Myocyte enhancer factor (MEF)-2 plays essential roles in T-cell transformation associated with HTLV-1 infection by stabilizing complex between tax and CREB. Retrovirology. 2015;12:23. 10.1186/s12977-015-0140-1
43 Lu J, McKinsey TA, Zhang C-L, Olson EN. Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases. Mol Cell. 2000;6:233–44. 10.1016/s1097-2765(00)00025-3
44 Jung C-C, Su H-J. Long-term allergen exposure induces adipose tissue inflammation and circulatory system injury. Cellular Immunol. 2016;303:34–42. 10.1016/j.cellimm.2016.03.002
45 Xue Z, Guo S, Liu X, Ma J, Zhu W, Zhou Y, et al. Impact of COPD or asthma on the risk of atrial fibrillation: A systematic review and meta-analysis. Front Cardiovasc Med. 2022;9:872446. 10.3389/fcvm.2022.872446
46 Goudis CA. Chronic obstructive pulmonary disease and atrial fibrillation: An unknown relationship. J Cardiol. 2017;69:699–705. 10.1016/j.jjcc.2016.12.013
47 Ganga HV, Nair SU, Puppala VK, Miller WL. Risk of newonset atrial fibrillation in elderly patients with the overlap syndrome: A retrospective cohort study. J Geriatr Cardiol. 2013;10:129–34. 10.3969/j.issn.1671-5411.2013.02.001
48 Yang X, Zhang L, Liu H, Shao Y, Zhang S. Cardiac sympathetic denervation suppresses atrial fibrillation and blood pressure in a chronic intermittent hypoxia rat model of obstructive sleep apnea. J Am Heart Assoc. 2019;8:e010254. 10.1161/JAHA.118.010254
49 Kang H, Bae BS, Kim JH, Jang HS, Lee BR, Jung BC. The relationship between chronic atrial fibrillation and reduced pulmonary function in cases of preserved left ventricular systolic function. Korean Circ J. 2009;39:372–7. 10.4070/kcj.2009.39.9.372
50 Simons SO, Elliott A, Sastry M, Hendriks JM, Arzt M, Rienstra M, et al. Chronic obstructive pulmonary disease and atrial fibrillation: An interdisciplinary perspective. Eur Heart J. 2021;42:532–40. 10.1093/eurheartj/ehaa822
51 R. Khan. Identifying and understanding the role of pulmonary vein activity in atrial fibrillation. Cardiovasc Res. 2004;64(3):387–94. 10.1016/j.cardiores.2004.07.025
52 Liu M, Chen R, Zheng Z, Xu S, Hou C, Ding Y, et al. Mechanisms of inflammatory microenvironment formation in cardiometabolic diseases: molecular and cellular perspectives. Front Cardiovasc Med. 2025; 11:1529903.
53 Liu T, Zeng J, Zhao X, Fu R, Peng L, Li X, et al. Relationship between vascular aging and left ventricular geometry in patients with obstructive sleep apnea hypopnea syndrome-related hypertension. Sci Rep. 2025; 15:6191
54 Edriss H, Denega T, Test V, Nugent K. Pulmonary vein stenosis complicating radiofrequency catheter ablation for atrial fibrillation: A literature review. Respir Med. 2016;117:215–22. 10.1016/j.rmed.2016.06.014