Нейроопосредованные и эндотелийзависимые механизмы формирования хронической обструктивной болезни легких
DOI: 10.26442/00403660.2020.03.000347
________________________________________________
Brodskaya T.A., Nevzorova V.A., Vasileva M.S., Lavrenyuk V.V. Endothelium-related and neuro-mediated mechanisms of emphysema development in chronic obstructive pulmonary disease. Therapeutic Archive. 2020; 92 (3): 116–124.
DOI: 10.26442/00403660.2020.03.000347
Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Ключевые слова: хроническая обструктивная болезнь легких, курение, эмфизема, эндотелий, сосуды, нейрокинины.
________________________________________________
Emphysema is one of the main manifestations of chronic obstructive pulmonary disease (COPD), and smoking is one of the most significant risk factors. The results of studies in humans and animals show the vascular endothelium initiates and modulates the main pathological processes in COPD and smoking is an important factor initiating, developing and persisting inflammation and remodeling of blood vessels and tissues, including the destruction of small respiratory tracts with the development of lung tissue destruction and emphysema. The latest studies describe mechanisms not just associated with the endothelium, but specific neuro-mediated mechanisms. There is reason to believe that neuro-mediated and neuro-similar mechanisms associated and not related to endothelial dysfunction may play the significant role in the pathogenesis of COPD and emphysema formation. Information about components and mechanisms of neurogenic inflammation in emphysema development is fragmentary and not systematized in the literature. It is described that long-term tobacco smoking can initiate processes not only of cells and tissues damage, but also become a trigger for excessive release of neurotransmitters, which entails whole cascades of adverse reactions that have an effect on emphysema formation. With prolonged and/or intensive stimulation of sensor fibers, excessive release of neuropeptides is accompanied by a number of plastic and destructive processes due to a cascade of pathological reactions of neurogenic inflammation, the main participants of which are classical neuropeptides and their receptors. The most important consequences can be the maintenance and stagnation of chronic inflammation, activation of the mechanisms of destruction and remodeling, inadequate repair processes in response to damage, resulting in irreversible loss of lung tissue. For future research, there is interest to evaluate the possibilities of therapeutic and prophylactic effects on neuro-mediated mechanisms of endothelial dysfunction and damage emphysema in COPD and smoking development.
Key words: chronic obstructive pulmonary disease, smoking, emphysema, endothelium, vessels, neurokinins.
2. Woodruff PG, Barr RG, Bleecker E, et al. Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function. N Engl J Med. 2016;374(19):1811-21. doi: 10.1056/nejmoa1505971
3. Regan EA, Lynch DA, Curran-Everett D, et al. Clinical and Radiologic Disease in Smokers With Normal Spirometry. JAMA Intern Med. 2015;175(9):1539. doi: 10.1001/jamainternmed.2015.2735
4. Nevzorova V, Brodskaya T, Zakharchuk N. Smoking, Respiratory Diseases and Endothelial Dysfunction. Endothelial Dysfunction – Old Concepts and New Challenges. 2018. doi: 10.5772/intechopen.
73555
5. Alford SK, Beek EJRV, Mclennan G, Hoffman EA. Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers. Proceed Nat Acad Sci. 2010;107(16):7485-90. doi: 10.1073/pnas.0913880107
6. Iyer KS, Newell JD, Jin D, et al. Quantitative Dual-Energy Computed Tomography Supports a Vascular Etiology of Smoking-induced Inflammatory Lung Disease. Am J Respir Crit Care Med. 2016;193(6):652-61. doi: 10.1164/rccm.201506-1196oc
7. Peinado VI, Pizarro S, Barberà JA. Pulmonary Vascular Involvement in COPD. Chest. 2008;134(4):808-14. doi: 10.1378/chest.08-0820
8. Sakao S, Voelkel NF, Tatsumi K. The vascular bed in COPD: pulmonary hypertension and pulmonary vascular alterations. Eur Respir Rev. 2014;23(133):350-5. doi: 10.1183/09059180.00007913
9. Бродская Т.А., Гельцер Б.И., Невзорова В.А. Артериальная ригидность и болезни органов дыхания (патофизиологические механизмы и клиническое значение). Владивосток: Дальнаука, 2008 [Brodskaya TA, Gel'tser BI, Nevzorova VA. Arterial stiffness and respiratory deseases (pathophysiological mechanisms and clinical significance). Vladivostok: Dal'nauka, 2008 (In Russ.)].
10. Cui M, Cui R, Liu K, et al. Associations of Tobacco Smoking with Impaired Endothelial Function: The Circulatory Risk in Communities Study (CIRCS). J Atherosclerosis Thrombosis. 2018;25(9):836-45. doi: 10.5551/jat.42150
11. García-Lucio J, Peinado VI, Jover LD, et al. Imbalance between endothelial damage and repair capacity in chronic obstructive pulmonary disease. Plos One. 2018;13(4). doi: 10.1371/journal.pone.0195724
12. Green CE, Turner AM. The role of the endothelium in asthma and chronic obstructive pulmonary disease (COPD). Respir Res. 2017;18(1). doi: 10.1186/s12931-017-0505-1
13. Huertas A, Guignabert C, Barberà JA, et al. Pulmonary vascular endothelium: the orchestra conductor in respiratory diseases. Eur Respir J. 2018;51(4):1700745. doi: 10.1183/13993003.00745-2017
14. Letsiou E, Bauer N. Endothelial Extracellular Vesicles in Pulmonary Function and Disease. Cur Topics Membranes Pulmonary Vasc Dis. 2018:197-256. doi: 10.1016/bs.ctm.2018.09.002
15. Lu Q, Gottlieb E, Rounds S. Effects of cigarette smoke on pulmonary endothelial cells. Am J Physiology-Lung Cell Molecular Physiol. 2018;314(5). doi: 10.1152/ajplung.00373.2017
16. Skurikhin EG, Krupin VA, Pershina OV, et al. Endothelial Progenitor Cells and Notch-1 Signaling as Markers of Alveolar Endothelium Regeneration in Pulmonary Emphysema. Bull Experim Biol Med. 2018;166(2):201-6. doi: 10.1007/s10517-018-4314-4
17. Atanasova KR, Reznikov LR. Neuropeptides in asthma, chronic obstructive pulmonary disease and cystic fibrosis. Respir Res. 2018;19(1). doi: 10.1186/s12931-018-0846-4
18. Calzetta L, Rogliani P, Facciolo F, et al. N-Acetylcysteine protects human bronchi by modulating the release of neurokinin A in an ex vivo model of COPD exacerbation. Biomed Pharmacother. 2018;103:1-8. doi: 10.1016/j.biopha.2018.04.011
19. Chavan SS, Pavlov VA, Tracey KJ. Mechanisms and Therapeutic Relevance of Neuro-immune Communication. Immunity. 2017;46(6):927-42. doi: 10.1016/j.immuni.2017.06.008
20. Бродская Т.А., Невзорова В.А., Гельцер Б.И., Моткина Е.В. Эндотелиальная дисфункция и болезни органов дыхания. Терапевтический архив. 2007;3(79):76-84 [Brodskaya TA, Nevzorova VA, Gel'tser BI, Motkina EV. Endothelial dysfunction and respiratory diseases. Therapeutic Archive. 2007;3(79):76-84 (In Russ.)]. PMID: 17526203
21. Polverino F, Celli BR, Owen CA. COPD as an endothelial disorder: endothelial injury linking lesions in the lungs and other organs? (2017 Grover Conference Series). Pulmon Circulation. 2018;8(1):204589401875852. doi: 10.1177/2045894018758528
22. Moro L, Pedone C, Scarlata S, et al. Endothelial Dysfunction in Chronic Obstructive Pulmonary Disease. Angiology. 2008;59(3):357-64. doi: 10.1177/0003319707306141
23. Dugac AV, Ruzic A, Samarzija M, et al. Persistent endothelial dysfunction turns the frequent exacerbator COPD from respiratory disorder into a progressive pulmonary and systemic vascular disease. Medical Hypotheses. 2015;84(2):155-8. doi: 10.1016/j.mehy.2014.11.017
24. Voelkel NF. Cigarette Smoke Is an Endothelial Cell Toxin. Am J Respir Crit Care Med. 2018;197(2):274. doi: 10.1164/rccm.201706-1123le
25. Yasuo M, Mizuno S, Kraskauskas D, et al. Hypoxia inducible factor-1 in human emphysema lung tissue. Eur Respir J. 2010;37(4):775-83. doi: 10.1183/09031936.00022910
26. Brodskaya T, Nevzorova V, Zakharchuk N, Repina N. Aortic stiffness and polymorphisms of collagen-1 type 1a gene in COPD patients.
J Lung Pulm Respir Res. 2018;5(3):81-5. doi: 10.15406/jlprr. 2018.05.00167
27. Kasahara Y, Tuder RM, Taraseviciene-Stewart L, et al. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Investigation. 2000;106(11):1311-9. doi: 10.1172/jci10259
28. Voelkel N, Cool C. Pulmonary vascular involvement in chronic obstructive pulmonary disease. Eur Respir J. 2003;22(Suppl. 46). doi: 10.1183/09031936.03.00000503
29. Tuder RM, Zhen L, Cho CY, et al. Oxidative Stress and Apoptosis Interact and Cause Emphysema Due to Vascular Endothelial Growth Factor Receptor Blockade. Am J Respir Cell Molecular Biol. 2003;29(1):88-97. doi: 10.1165/rcmb.2002-0228oc
30. Kasahara Y, Tuder RM, Cool CD, et al. Endothelial Cell Death and Decreased Expression of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor 2 in Emphysema. Am J Respir Crit Care Med. 2001;163(3):737-44. doi: 10.1164/ajrccm.163.3.2002117
31. Lee J-H. Decreased Number of Circulating Endothelial Progenitor Cells in Patients with Emphysema. Proceed Am Thoracic Soc. 2006;3(6):545-45. doi: 10.1513/pats.200603-047ms
32. Yamada M, Ichinose M. The cholinergic anti-inflammatory pathway: an innovative treatment strategy for respiratory diseases and their comorbidities. Cur Opinion Pharmacol. 2018;40:18-25. doi: 10.1016/j.coph.2017.12.003
33. Gupta M, Bansal V, Chhabra SK. Autonomic Dysfunction In Chronic Obstructive Pulmonary Disease. B41 Copd And Associated Comorbidities. 2011. doi: 10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a2995
34. Mohammed J, Meeus M, Derom E, et al. Evidence for Autonomic Function and Its Influencing Factors in Subjects With COPD: A Systematic Review. Respir Care. 2015:60(12):1841-51. doi: 10.4187/respcare. 04174
35. Audrit KJ, Delventhal L, Aydin Ö, Nassenstein C. The nervous system of airways and its remodeling in inflammatory lung diseases. Cell Tissue Res. 2017;367(3):571-90. doi: 10.1007/s00441-016-2559-7
36. Voisin T, Bouvier A, Chiu IM. Neuro-immune interactions in allergic diseases: novel targets for therapeutics. Intern Immunol. 2017;29(6):247-61. doi: 10.1093/intimm/dxx040
37. Ricciardolo FL, Folkerts G, Folino A, Mognetti B. Bradykinin in asthma: Modulation of airway inflammation and remodelling. Eur
J Pharmacol. 2018;827:181-8. doi: 10.1016/j.ejphar.2018.03.017
38. Burbach JPH. What Are Neuropeptides? Methods Molecular Biol Neuropeptides. 2011:1-36. doi: 10.1007/978-1-61779-310-3_1
39. Burbach JPH. Neuropeptides from concept to online database www.neuropeptides.nl. Eur J Pharmacol. 2010;626(1):27-48. doi: 10.1016/ j.ejphar.2009.10.015
40. Merighi A, Salio C, Ferrini F, Lossi L. Neuromodulatory function of neuropeptides in the normal CNS. J Chem Neuroanat. 2011;42(4):276-87. doi: 10.1016/j.jchemneu.2011.02.001
41. Coles SJ, Bhaskar KR, Osullivan DD, et al. Airway Mucus: Composition and Regulation of its Secretion by Neuropeptides in vitro. Ciba Foundation Symposium 109 – Mucus and Mucosa Novartis Foundation Symposia. 2008:40-60. doi:10.1002/9780470720905.ch4
42. Bradley SJ, Wiegman CH, Iglesias MM, et al. Mapping physiological G protein-coupled receptor signaling pathways reveals a role for receptor phosphorylation in airway contraction. Proceed Nat Acad Sci. 2016;113(16):4524-9. doi: 10.1073/pnas.1521706113
43. Swert KOD, Joos GF. Extending the understanding of sensory neuropeptides. Eur J Pharmacol. 2006;533(1-3):171-81. doi: 10.1016/
j.ejphar.2005.12.066
44. Pedragosa-Badia X, Stichel J, Beck-Sickinger AG. Neuropeptide Y receptors: how to get subtype selectivity. Frontiers Endocrinol. 2013;4. doi: 10.3389/fendo.2013.00005
45. Yi M, Li H, Wu Z, et al. A Promising Therapeutic Target for Metabolic Diseases: Neuropeptide Y Receptors in Humans. Cell Physiol Biochem. 2017;45(1):88-107. doi: 10.1159/000486225
46. Jensen RT, Battey JF, Spindel ER, Benya RV. International Union of Pharmacology. LXVIII. Mammalian Bombesin Receptors: Nomenclature, Distribution, Pharmacology, Signaling, and Functions in Normal and Disease States. Pharmacol Rev. 2008;60(1):1-42. doi: 10.1124/pr.107.07108
47. Xu R, Li Q, Zhou J, et al. Secretoneurin Induces Airway Mucus Hypersecretion by Enhancing the Binding of EGF to NRP1. Cell Physiol Biochem. 2014;33(2):446-56. doi: 10.1159/000358625
48. Branchfield K, Nantie L, Verheyden JM, et al. Pulmonary neuroendocrine cells function as airway sensors to control lung immune response. Science. 2016;351(6274):707-10. doi: 10.1126/science.aad7969
49. Sui P, Wiesner DL, Xu J, et al. Pulmonary neuroendocrine cells amplify allergic asthma responses. Science. 2018;360(6393). doi: 10.1126/
science.aan8546
50. Cutz E, Yeger H, Pan J. Pulmonary Neuroendocrine Cell System in Pediatric Lung Disease – Recent Advances. Pediatric Developmental Pathology. 2007;10(6):419-35. doi: 10.2350/07-04-0267.1
51. Pan J, Copland I, Post M, et al. Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells: implications for lung development. Am J Physiology-Lung Cell Molecular Physiol. 2006;290(1). doi: 10.1152/ajplung.00167.2005
52. Weichselbaum M, Sparrow MP, Hamilton EJ, et al. A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium. Respir Res. 2005;6(1). doi: 10.1186/1465-9921-6-115
53. Steinhoff MS, Mentzer BV, Geppetti P, et al. Tachykinins and Their Receptors: Contributions to Physiological Control and the Mechanisms of Disease. Physiol Rev. 2014;94(1):265-301. doi: 10.1152/physrev. 00031.2013
54. Xu J, Xu F, Lin Y. Cigarette Smoke Synergizes Lipopolysaccharide-Induced InterIeukin-1β and Tumor Necrosis Factor-α Secretion from Macrophages via Substance P-Mediated Nuclear Factor-κB Activation. Am J Respir Cell Molecular Biol. 2011;44(3):302-8. doi: 10.1165/rcmb.2009-0288oc
55. Choi JY, Khansaheb M, Joo NS, et al. Substance P stimulates human airway submucosal gland secretion mainly via a CFTR-dependent process. J Clin Investigation. 2009;119(5):1189-200. doi: 10.1172/jci37284
56. Khansaheb M, Choi JY, Joo NS, et al. Properties of substance P-stimulated mucus secretion from porcine tracheal submucosal glands. Am
J Physiology-Lung Cell Molecular Physiol. 2011;300(3). doi: 10.1152/ajplung.00372.2010
57. Garcia-Recio S, Gascón P. Biological and Pharmacological Aspects of the NK1-Receptor. BioMed Res Intern. 2015;2015:1-14. doi: 10.1155/2015/495704
58. Dinh Q, Klapp B, Fischer A. Die sensible Atemwegsinnervation und die Tachykinine bei Asthma und chronisch-obstruktiver Lungenerkrankung (COPD). Pneumologie. 2006;60(02):80-5. doi: 10.1055/s-2005-915587
59. Hens G, Raap U, Vanoirbeek J, et al. Selective Nasal Allergen Provocation Induces Substance P-mediated Bronchial Hyperresponsiveness. Am J Respir Cell Molecular Biol. 2011;44(4):517-23. doi: 10.1165/rcmb.2009-0425oc
60. Swert KOD, Bracke KR, Demoor T, et al. Role of the tachykinin NK1 receptor in a murine model of cigarette smoke-induced pulmonary inflammation. Respir Res. 2009;10(1). doi: 10.1186/1465-9921-10-37
61. Bera MM, Lu B, Martin TR, et al. Th17 Cytokines Are Critical for Respiratory Syncytial Virus-Associated Airway Hyperreponsiveness through Regulation by Complement C3a and Tachykinins. J Immunol. 2011;187(8):4245-55. doi: 10.4049/jimmunol.1101789
62. Goravanahally MP, Hubbs AF, Fedan JS, et al. Diacetyl Increases Sensory Innervation and Substance P Production in Rat Trachea. Toxicol Pathol. 2013;42(3):582-90. doi: 10.1177/0192623313493689
63. Manorak W, Idahosa C, Gupta K, et al. Upregulation of Mas-related G Protein coupled receptor X2 in asthmatic lung mast cells and its activation by the novel neuropeptide hemokinin-1. Respir Res. 2018;19(1). doi: 10.1186/s12931-017-0698-3
64. Kwong K, Wu Z-X, Kashon ML, et al. Chronic Smoking Enhances Tachykinin Synthesis and Airway Responsiveness in Guinea Pigs. Am
J Respir Cell Molecular Biol. 2001;25(3):299-305. doi: 10.1165/ajrcmb.25.3.4557
65. Phillips JE, Hey JA, Corboz MR. Tachykinin NK3 and NK1receptor activation elicits secretion from porcine airway submucosal glands. Br
J Pharmacol. 2003;138(1):254-60. doi: 10.1038/sj.bjp.0705029
66. Vergnolle N, Cenac N, Altier C, et al. A role for transient receptor potential vanilloid 4 in tonicity-induced neurogenic inflammation. Br
J Pharmacol. 2010;159(5):1161-73. doi: 10.1111/j.1476-5381.2009. 00590.x
67. Patacchini R, Lecci A, Holzer P, Maggi CA. Newly discovered tachykinins raise new questions about their peripheral roles and the tachykinin nomenclature. Trends Pharmacol Sci. 2004;25(1):1-3. doi: 10.1016/j.tips.2003.11.005
68. Kim J-S, Okamoto K, Arima S, Rubin BK. Vasoactive intestinal peptide stimulates mucus secretion, but nitric oxide has no effect on mucus secretion in the ferret trachea. J Applied Physiol. 2006;101(2):486-91. doi: 10.1152/japplphysiol.01264.2005
69. Paulis L, Rajkovicova R, Simko F. New Developments in the Pharmacological Treatment of Hypertension: Dead-End or a Glimmer at the Horizon? Cur Hypertension Rep. 2015;17(6). doi: 10.1007/s11906-015-0557-x
70. Burian B, Angela S, Nadler B, et al. Inhaled Vasoactive Intestinal Peptide (Vip) Improves The 6-Minute Walk Test And Quality Of Life In Patients With Copd: The Vip/copd-Trial. Chest. 2006;130(4). doi: 10.1378/chest.130.4_meetingabstracts.121s-c
71. Kim V, Criner GJ. Chronic Bronchitis and Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2013;187(3):228-37. doi: 10.1164/rccm.201210-1843ci
72. Miotto D. Vasoactive intestinal peptide receptors in the airways of smokers with chronic bronchitis. Eur Respir J. 2004;24(6):958-63. doi: 10.1183/09031936.04.10031504
73. Springer J, Geppetti P, Fischer A, Groneberg DA. Calcitonin gene-related peptide as inflammatory mediator. Pulm Pharmacol Ther. 2003;16(3):121-30. doi: 10.1016/s1094-5539(03)00049-x
74. Gu X, Karp PH, Brody SL, et al. Chemosensory Functions for Pulmonary Neuroendocrine Cells. Am J Respir Cell Molecular Biol. 2014;50(3):637-46. doi: 10.1165/rcmb.2013-0199oc
75. Groneberg DA, Folkerts G, Peiser C, et al. Neuropeptide Y (NPY). Pulm Pharmacol Ther. 2004;17(4):173-80. doi: 10.1016/j.pupt.2004.04.003
76. Wheway J, Herzog H, Mackay F. NPY and Receptors in Immune and Inflammatory Diseases. Cur Topics Med Chem. 2007;7(17):1743-52. doi: 10.2174/156802607782341046
77. Makinde TO, Steininger R, Agrawal DK. Expression Of NPY And NPY Receptors In Airway Structural And Inflammatory Cells In Allergic Asthma. C37 Mediators Of Asthma And Allergic Lung Disease. 2012. doi: 10.1164/ajrccm-conference.2012.185.1_meetingabstracts. a4284
78. Li S, Koziol-White C, Jude J, et al. Epithelium-generated neuropeptide Y induces smooth muscle contraction to promote airway hyperresponsiveness. J Clin Investigation. 2016;126(5):1978-82. doi: 10.1172/ jci81389
79. Joos G, Oconnor B. Indirect airway challenges. Eur Respir J. 2003;21(6):1050-68. doi: 10.1183/09031936.03.00008403
80. Mapp CE, Miotto D, Braccioni F, et al. The Distribution of Neurokinin-1 and Neurokinin-2 Receptors in Human Central Airways. Am J Respir Crit Care Med. 2000;161(1):207-15. doi: 10.1164/ajrccm.161.1. 9903137
81. Wu Z-X, Benders KB, Hunter DD, Dey RD. Early postnatal exposure of mice to side-steam tobacco smoke increases neuropeptide Y in lung. Am J Physiology-Lung Cell Molecular Physiol. 2012;302(1). doi: 10.1152/ajplung.00071.2011
82. Thangaratnarajah C, Dinger K, Vohlen C, et al. Novel role of NPY in neuroimmune interaction and lung growth after intrauterine growth restriction. Am J Physiology-Lung Cell Molecular Physiol. 2017;313(3). doi: 10.1152/ajplung.00432.2016
83. Fleming MS, Ramos D, Han SB, et al. The Majority of Dorsal Spinal Cord Gastrin Releasing Peptide is Synthesized Locally Whereas Neuromedin B is Highly Expressed in Pain- and Itch-Sensing Somatosensory Neurons. Molecular Pain. 2012;8. doi: 10.1186/1744-8069-8-52
84. Liu H, Peng L, Liu C, et al. Activation of Bombesin Receptor Subtype-3 Promotes Antigen-Presenting Action in Human Bronchial Epithelial Cells. Int Arch Allergy Immunol. 2018;175(1-2):53-60. doi: 10.1159/000485895
85. Helle KB, Metz-Boutigue M-H, Cerra MC, Angelone T. Chromogranins: from discovery to current times. Pflügers Archiv – Eur J Physiol. 2017;470(1):143-54. doi: 10.1007/s00424-017-2027-6
86. Sorhaug S, Langhammer A, Waldum HL, et al. Increased serum levels of chromogranin A in male smokers with airway obstruction. Eur Respir J. 2006;28(3):542-8. doi: 10.1183/09031936.06.00092205
87. Ottesen AH, Carlson CR, Edwards AG, et al. Secretoneurin, a Novel Endogenous CaMKII Inhibitor, Augments Cardiomyocyte Calcium Handling and Inhibits Arrhythmogenic Calcium Release. Biophysical J. 2015;108(2). doi: 10.1016/j.bpj.2014.11.1863
88. Маслюков П.М., Емануйлов А.И., Ноздрачев А.Д. Возрастные изменения нейротрансмиттерного состава нейронов симпатических узлов. Успехи геронтологии. 2016;29(3):442–53 [Maslyukov PM, Emanuilov AI, Nozdrachev AD. Developmental changes of neurotransmitter properties in sympathetic neurons. Uspekhi gerontologii. 2016;29(3):442–53 (In Russ.)]. PMID: 28849877
89. Невзорова В.А., Тилик Т.В., Гилифанов Е.А. Роль матриксных металлопротеиназ в формировании морфофункционального дисбаланса воздухоносных путей при хронической обструктивной болезни легких. Тихоокеанский мед. журн. 2011;2:9-13 [Nevzorova VA,
Tilik TV, Gilifanov EA. Role of matrix metalloproteinases in forming morphofunctional imbalance of airways in case of chronic obstructive lung disease. Tikhookeanskii med. zhurn. 2011;2:9-13 (In Russ.)].
90. Chelluboina B, Nalamolu KR, Klopfenstein JD, et al. MMP-12, a Promising Therapeutic Target for Neurological Diseases. Molecular Neurobiol. 2017;55(2):1405-9. doi: 10.1007/s12035-017-0418-5
91. Xu J, Xu F, Barrett E. Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice. Am J Physiology-Lung Cell Molecular Physiol. 2008;295(1). doi: 10.1152/ajplung. 00282.2007
92. Chaouat A. Pulmonary hypertension in COPD. Respiratory Medicine: COPD Update. 2007;3(1):18-9. doi: 10.1016/s1745-0454(07)70048-5
93. Springer J, Amadesi S, Trevisani M, et al. Effects of alpha calcitonin gene-related peptide in human bronchial smooth muscle and pulmonary artery. Regulatory Peptides. 2004;118(3):127-34. doi: 10.1016/j.regpep.2003.11.006
94. Roos AB, Berg T, Nord M. A Relationship between Epithelial Maturation, Bronchopulmonary Dysplasia, and Chronic Obstructive Pulmonary Disease. Pulmonary Med. 2012;2012:1-10. doi: 10.1155/2012/196194
________________________________________________
1. Global initiative for Chronic Obstructive Pulmonary Disease 2018. http://www.goldcopd.org
2. Woodruff PG, Barr RG, Bleecker E, et al. Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function. N Engl J Med. 2016;374(19):1811-21. doi: 10.1056/nejmoa1505971
3. Regan EA, Lynch DA, Curran-Everett D, et al. Clinical and Radiologic Disease in Smokers With Normal Spirometry. JAMA Intern Med. 2015;175(9):1539. doi: 10.1001/jamainternmed.2015.2735
4. Nevzorova V, Brodskaya T, Zakharchuk N. Smoking, Respiratory Diseases and Endothelial Dysfunction. Endothelial Dysfunction – Old Concepts and New Challenges. 2018. doi: 10.5772/intechopen.
73555
5. Alford SK, Beek EJRV, Mclennan G, Hoffman EA. Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers. Proceed Nat Acad Sci. 2010;107(16):7485-90. doi: 10.1073/pnas.0913880107
6. Iyer KS, Newell JD, Jin D, et al. Quantitative Dual-Energy Computed Tomography Supports a Vascular Etiology of Smoking-induced Inflammatory Lung Disease. Am J Respir Crit Care Med. 2016;193(6):652-61. doi: 10.1164/rccm.201506-1196oc
7. Peinado VI, Pizarro S, Barberà JA. Pulmonary Vascular Involvement in COPD. Chest. 2008;134(4):808-14. doi: 10.1378/chest.08-0820
8. Sakao S, Voelkel NF, Tatsumi K. The vascular bed in COPD: pulmonary hypertension and pulmonary vascular alterations. Eur Respir Rev. 2014;23(133):350-5. doi: 10.1183/09059180.00007913
9. Brodskaya TA, Gel'tser BI, Nevzorova VA. Arterial stiffness and respiratory deseases (pathophysiological mechanisms and clinical significance). Vladivostok: Dal'nauka, 2008 (In Russ.)
10. Cui M, Cui R, Liu K, et al. Associations of Tobacco Smoking with Impaired Endothelial Function: The Circulatory Risk in Communities Study (CIRCS). J Atherosclerosis Thrombosis. 2018;25(9):836-45. doi: 10.5551/jat.42150
11. García-Lucio J, Peinado VI, Jover LD, et al. Imbalance between endothelial damage and repair capacity in chronic obstructive pulmonary disease. Plos One. 2018;13(4). doi: 10.1371/journal.pone.0195724
12. Green CE, Turner AM. The role of the endothelium in asthma and chronic obstructive pulmonary disease (COPD). Respir Res. 2017;18(1). doi: 10.1186/s12931-017-0505-1
13. Huertas A, Guignabert C, Barberà JA, et al. Pulmonary vascular endothelium: the orchestra conductor in respiratory diseases. Eur Respir J. 2018;51(4):1700745. doi: 10.1183/13993003.00745-2017
14. Letsiou E, Bauer N. Endothelial Extracellular Vesicles in Pulmonary Function and Disease. Cur Topics Membranes Pulmonary Vasc Dis. 2018:197-256. doi: 10.1016/bs.ctm.2018.09.002
15. Lu Q, Gottlieb E, Rounds S. Effects of cigarette smoke on pulmonary endothelial cells. Am J Physiology-Lung Cell Molecular Physiol. 2018;314(5). doi: 10.1152/ajplung.00373.2017
16. Skurikhin EG, Krupin VA, Pershina OV, et al. Endothelial Progenitor Cells and Notch-1 Signaling as Markers of Alveolar Endothelium Regeneration in Pulmonary Emphysema. Bull Experim Biol Med. 2018;166(2):201-6. doi: 10.1007/s10517-018-4314-4
17. Atanasova KR, Reznikov LR. Neuropeptides in asthma, chronic obstructive pulmonary disease and cystic fibrosis. Respir Res. 2018;19(1). doi: 10.1186/s12931-018-0846-4
18. Calzetta L, Rogliani P, Facciolo F, et al. N-Acetylcysteine protects human bronchi by modulating the release of neurokinin A in an ex vivo model of COPD exacerbation. Biomed Pharmacother. 2018;103:1-8. doi: 10.1016/j.biopha.2018.04.011
19. Chavan SS, Pavlov VA, Tracey KJ. Mechanisms and Therapeutic Relevance of Neuro-immune Communication. Immunity. 2017;46(6):927-42. doi: 10.1016/j.immuni.2017.06.008
20. Brodskaya TA, Nevzorova VA, Gel'tser BI, Motkina EV. Endothelial dysfunction and respiratory diseases. Therapeutic Archive. 2007;3(79):76-84 (In Russ.) PMID: 17526203
21. Polverino F, Celli BR, Owen CA. COPD as an endothelial disorder: endothelial injury linking lesions in the lungs and other organs? (2017 Grover Conference Series). Pulmon Circulation. 2018;8(1):204589401875852. doi: 10.1177/2045894018758528
22. Moro L, Pedone C, Scarlata S, et al. Endothelial Dysfunction in Chronic Obstructive Pulmonary Disease. Angiology. 2008;59(3):357-64. doi: 10.1177/0003319707306141
23. Dugac AV, Ruzic A, Samarzija M, et al. Persistent endothelial dysfunction turns the frequent exacerbator COPD from respiratory disorder into a progressive pulmonary and systemic vascular disease. Medical Hypotheses. 2015;84(2):155-8. doi: 10.1016/j.mehy.2014.11.017
24. Voelkel NF. Cigarette Smoke Is an Endothelial Cell Toxin. Am J Respir Crit Care Med. 2018;197(2):274. doi: 10.1164/rccm.201706-1123le
25. Yasuo M, Mizuno S, Kraskauskas D, et al. Hypoxia inducible factor-1 in human emphysema lung tissue. Eur Respir J. 2010;37(4):775-83. doi: 10.1183/09031936.00022910
26. Brodskaya T, Nevzorova V, Zakharchuk N, Repina N. Aortic stiffness and polymorphisms of collagen-1 type 1a gene in COPD patients.
J Lung Pulm Respir Res. 2018;5(3):81-5. doi: 10.15406/jlprr. 2018.05.00167
27. Kasahara Y, Tuder RM, Taraseviciene-Stewart L, et al. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Investigation. 2000;106(11):1311-9. doi: 10.1172/jci10259
28. Voelkel N, Cool C. Pulmonary vascular involvement in chronic obstructive pulmonary disease. Eur Respir J. 2003;22(Suppl. 46). doi: 10.1183/09031936.03.00000503
29. Tuder RM, Zhen L, Cho CY, et al. Oxidative Stress and Apoptosis Interact and Cause Emphysema Due to Vascular Endothelial Growth Factor Receptor Blockade. Am J Respir Cell Molecular Biol. 2003;29(1):88-97. doi: 10.1165/rcmb.2002-0228oc
30. Kasahara Y, Tuder RM, Cool CD, et al. Endothelial Cell Death and Decreased Expression of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor 2 in Emphysema. Am J Respir Crit Care Med. 2001;163(3):737-44. doi: 10.1164/ajrccm.163.3.2002117
31. Lee J-H. Decreased Number of Circulating Endothelial Progenitor Cells in Patients with Emphysema. Proceed Am Thoracic Soc. 2006;3(6):545-45. doi: 10.1513/pats.200603-047ms
32. Yamada M, Ichinose M. The cholinergic anti-inflammatory pathway: an innovative treatment strategy for respiratory diseases and their comorbidities. Cur Opinion Pharmacol. 2018;40:18-25. doi: 10.1016/j.coph.2017.12.003
33. Gupta M, Bansal V, Chhabra SK. Autonomic Dysfunction In Chronic Obstructive Pulmonary Disease. B41 Copd And Associated Comorbidities. 2011. doi: 10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a2995
34. Mohammed J, Meeus M, Derom E, et al. Evidence for Autonomic Function and Its Influencing Factors in Subjects With COPD: A Systematic Review. Respir Care. 2015:60(12):1841-51. doi: 10.4187/respcare. 04174
35. Audrit KJ, Delventhal L, Aydin Ö, Nassenstein C. The nervous system of airways and its remodeling in inflammatory lung diseases. Cell Tissue Res. 2017;367(3):571-90. doi: 10.1007/s00441-016-2559-7
36. Voisin T, Bouvier A, Chiu IM. Neuro-immune interactions in allergic diseases: novel targets for therapeutics. Intern Immunol. 2017;29(6):247-61. doi: 10.1093/intimm/dxx040
37. Ricciardolo FL, Folkerts G, Folino A, Mognetti B. Bradykinin in asthma: Modulation of airway inflammation and remodelling. Eur
J Pharmacol. 2018;827:181-8. doi: 10.1016/j.ejphar.2018.03.017
38. Burbach JPH. What Are Neuropeptides? Methods Molecular Biol Neuropeptides. 2011:1-36. doi: 10.1007/978-1-61779-310-3_1
39. Burbach JPH. Neuropeptides from concept to online database www.neuropeptides.nl. Eur J Pharmacol. 2010;626(1):27-48. doi: 10.1016/ j.ejphar.2009.10.015
40. Merighi A, Salio C, Ferrini F, Lossi L. Neuromodulatory function of neuropeptides in the normal CNS. J Chem Neuroanat. 2011;42(4):276-87. doi: 10.1016/j.jchemneu.2011.02.001
41. Coles SJ, Bhaskar KR, Osullivan DD, et al. Airway Mucus: Composition and Regulation of its Secretion by Neuropeptides in vitro. Ciba Foundation Symposium 109 – Mucus and Mucosa Novartis Foundation Symposia. 2008:40-60. doi:10.1002/9780470720905.ch4
42. Bradley SJ, Wiegman CH, Iglesias MM, et al. Mapping physiological G protein-coupled receptor signaling pathways reveals a role for receptor phosphorylation in airway contraction. Proceed Nat Acad Sci. 2016;113(16):4524-9. doi: 10.1073/pnas.1521706113
43. Swert KOD, Joos GF. Extending the understanding of sensory neuropeptides. Eur J Pharmacol. 2006;533(1-3):171-81. doi: 10.1016/
j.ejphar.2005.12.066
44. Pedragosa-Badia X, Stichel J, Beck-Sickinger AG. Neuropeptide Y receptors: how to get subtype selectivity. Frontiers Endocrinol. 2013;4. doi: 10.3389/fendo.2013.00005
45. Yi M, Li H, Wu Z, et al. A Promising Therapeutic Target for Metabolic Diseases: Neuropeptide Y Receptors in Humans. Cell Physiol Biochem. 2017;45(1):88-107. doi: 10.1159/000486225
46. Jensen RT, Battey JF, Spindel ER, Benya RV. International Union of Pharmacology. LXVIII. Mammalian Bombesin Receptors: Nomenclature, Distribution, Pharmacology, Signaling, and Functions in Normal and Disease States. Pharmacol Rev. 2008;60(1):1-42. doi: 10.1124/pr.107.07108
47. Xu R, Li Q, Zhou J, et al. Secretoneurin Induces Airway Mucus Hypersecretion by Enhancing the Binding of EGF to NRP1. Cell Physiol Biochem. 2014;33(2):446-56. doi: 10.1159/000358625
48. Branchfield K, Nantie L, Verheyden JM, et al. Pulmonary neuroendocrine cells function as airway sensors to control lung immune response. Science. 2016;351(6274):707-10. doi: 10.1126/science.aad7969
49. Sui P, Wiesner DL, Xu J, et al. Pulmonary neuroendocrine cells amplify allergic asthma responses. Science. 2018;360(6393). doi: 10.1126/
science.aan8546
50. Cutz E, Yeger H, Pan J. Pulmonary Neuroendocrine Cell System in Pediatric Lung Disease – Recent Advances. Pediatric Developmental Pathology. 2007;10(6):419-35. doi: 10.2350/07-04-0267.1
51. Pan J, Copland I, Post M, et al. Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells: implications for lung development. Am J Physiology-Lung Cell Molecular Physiol. 2006;290(1). doi: 10.1152/ajplung.00167.2005
52. Weichselbaum M, Sparrow MP, Hamilton EJ, et al. A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium. Respir Res. 2005;6(1). doi: 10.1186/1465-9921-6-115
53. Steinhoff MS, Mentzer BV, Geppetti P, et al. Tachykinins and Their Receptors: Contributions to Physiological Control and the Mechanisms of Disease. Physiol Rev. 2014;94(1):265-301. doi: 10.1152/physrev. 00031.2013
54. Xu J, Xu F, Lin Y. Cigarette Smoke Synergizes Lipopolysaccharide-Induced InterIeukin-1β and Tumor Necrosis Factor-α Secretion from Macrophages via Substance P-Mediated Nuclear Factor-κB Activation. Am J Respir Cell Molecular Biol. 2011;44(3):302-8. doi: 10.1165/rcmb.2009-0288oc
55. Choi JY, Khansaheb M, Joo NS, et al. Substance P stimulates human airway submucosal gland secretion mainly via a CFTR-dependent process. J Clin Investigation. 2009;119(5):1189-200. doi: 10.1172/jci37284
56. Khansaheb M, Choi JY, Joo NS, et al. Properties of substance P-stimulated mucus secretion from porcine tracheal submucosal glands. Am
J Physiology-Lung Cell Molecular Physiol. 2011;300(3). doi: 10.1152/ajplung.00372.2010
57. Garcia-Recio S, Gascón P. Biological and Pharmacological Aspects of the NK1-Receptor. BioMed Res Intern. 2015;2015:1-14. doi: 10.1155/2015/495704
58. Dinh Q, Klapp B, Fischer A. Die sensible Atemwegsinnervation und die Tachykinine bei Asthma und chronisch-obstruktiver Lungenerkrankung (COPD). Pneumologie. 2006;60(02):80-5. doi: 10.1055/s-2005-915587
59. Hens G, Raap U, Vanoirbeek J, et al. Selective Nasal Allergen Provocation Induces Substance P-mediated Bronchial Hyperresponsiveness. Am J Respir Cell Molecular Biol. 2011;44(4):517-23. doi: 10.1165/rcmb.2009-0425oc
60. Swert KOD, Bracke KR, Demoor T, et al. Role of the tachykinin NK1 receptor in a murine model of cigarette smoke-induced pulmonary inflammation. Respir Res. 2009;10(1). doi: 10.1186/1465-9921-10-37
61. Bera MM, Lu B, Martin TR, et al. Th17 Cytokines Are Critical for Respiratory Syncytial Virus-Associated Airway Hyperreponsiveness through Regulation by Complement C3a and Tachykinins. J Immunol. 2011;187(8):4245-55. doi: 10.4049/jimmunol.1101789
62. Goravanahally MP, Hubbs AF, Fedan JS, et al. Diacetyl Increases Sensory Innervation and Substance P Production in Rat Trachea. Toxicol Pathol. 2013;42(3):582-90. doi: 10.1177/0192623313493689
63. Manorak W, Idahosa C, Gupta K, et al. Upregulation of Mas-related G Protein coupled receptor X2 in asthmatic lung mast cells and its activation by the novel neuropeptide hemokinin-1. Respir Res. 2018;19(1). doi: 10.1186/s12931-017-0698-3
64. Kwong K, Wu Z-X, Kashon ML, et al. Chronic Smoking Enhances Tachykinin Synthesis and Airway Responsiveness in Guinea Pigs. Am
J Respir Cell Molecular Biol. 2001;25(3):299-305. doi: 10.1165/ajrcmb.25.3.4557
65. Phillips JE, Hey JA, Corboz MR. Tachykinin NK3 and NK1receptor activation elicits secretion from porcine airway submucosal glands. Br
J Pharmacol. 2003;138(1):254-60. doi: 10.1038/sj.bjp.0705029
66. Vergnolle N, Cenac N, Altier C, et al. A role for transient receptor potential vanilloid 4 in tonicity-induced neurogenic inflammation. Br
J Pharmacol. 2010;159(5):1161-73. doi: 10.1111/j.1476-5381.2009. 00590.x
67. Patacchini R, Lecci A, Holzer P, Maggi CA. Newly discovered tachykinins raise new questions about their peripheral roles and the tachykinin nomenclature. Trends Pharmacol Sci. 2004;25(1):1-3. doi: 10.1016/j.tips.2003.11.005
68. Kim J-S, Okamoto K, Arima S, Rubin BK. Vasoactive intestinal peptide stimulates mucus secretion, but nitric oxide has no effect on mucus secretion in the ferret trachea. J Applied Physiol. 2006;101(2):486-91. doi: 10.1152/japplphysiol.01264.2005
69. Paulis L, Rajkovicova R, Simko F. New Developments in the Pharmacological Treatment of Hypertension: Dead-End or a Glimmer at the Horizon? Cur Hypertension Rep. 2015;17(6). doi: 10.1007/s11906-015-0557-x
70. Burian B, Angela S, Nadler B, et al. Inhaled Vasoactive Intestinal Peptide (Vip) Improves The 6-Minute Walk Test And Quality Of Life In Patients With Copd: The Vip/copd-Trial. Chest. 2006;130(4). doi: 10.1378/chest.130.4_meetingabstracts.121s-c
71. Kim V, Criner GJ. Chronic Bronchitis and Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2013;187(3):228-37. doi: 10.1164/rccm.201210-1843ci
72. Miotto D. Vasoactive intestinal peptide receptors in the airways of smokers with chronic bronchitis. Eur Respir J. 2004;24(6):958-63. doi: 10.1183/09031936.04.10031504
73. Springer J, Geppetti P, Fischer A, Groneberg DA. Calcitonin gene-related peptide as inflammatory mediator. Pulm Pharmacol Ther. 2003;16(3):121-30. doi: 10.1016/s1094-5539(03)00049-x
74. Gu X, Karp PH, Brody SL, et al. Chemosensory Functions for Pulmonary Neuroendocrine Cells. Am J Respir Cell Molecular Biol. 2014;50(3):637-46. doi: 10.1165/rcmb.2013-0199oc
75. Groneberg DA, Folkerts G, Peiser C, et al. Neuropeptide Y (NPY). Pulm Pharmacol Ther. 2004;17(4):173-80. doi: 10.1016/j.pupt.2004.04.003
76. Wheway J, Herzog H, Mackay F. NPY and Receptors in Immune and Inflammatory Diseases. Cur Topics Med Chem. 2007;7(17):1743-52. doi: 10.2174/156802607782341046
77. Makinde TO, Steininger R, Agrawal DK. Expression Of NPY And NPY Receptors In Airway Structural And Inflammatory Cells In Allergic Asthma. C37 Mediators Of Asthma And Allergic Lung Disease. 2012. doi: 10.1164/ajrccm-conference.2012.185.1_meetingabstracts. a4284
78. Li S, Koziol-White C, Jude J, et al. Epithelium-generated neuropeptide Y induces smooth muscle contraction to promote airway hyperresponsiveness. J Clin Investigation. 2016;126(5):1978-82. doi: 10.1172/ jci81389
79. Joos G, Oconnor B. Indirect airway challenges. Eur Respir J. 2003;21(6):1050-68. doi: 10.1183/09031936.03.00008403
80. Mapp CE, Miotto D, Braccioni F, et al. The Distribution of Neurokinin-1 and Neurokinin-2 Receptors in Human Central Airways. Am J Respir Crit Care Med. 2000;161(1):207-15. doi: 10.1164/ajrccm.161.1. 9903137
81. Wu Z-X, Benders KB, Hunter DD, Dey RD. Early postnatal exposure of mice to side-steam tobacco smoke increases neuropeptide Y in lung. Am J Physiology-Lung Cell Molecular Physiol. 2012;302(1). doi: 10.1152/ajplung.00071.2011
82. Thangaratnarajah C, Dinger K, Vohlen C, et al. Novel role of NPY in neuroimmune interaction and lung growth after intrauterine growth restriction. Am J Physiology-Lung Cell Molecular Physiol. 2017;313(3). doi: 10.1152/ajplung.00432.2016
83. Fleming MS, Ramos D, Han SB, et al. The Majority of Dorsal Spinal Cord Gastrin Releasing Peptide is Synthesized Locally Whereas Neuromedin B is Highly Expressed in Pain- and Itch-Sensing Somatosensory Neurons. Molecular Pain. 2012;8. doi: 10.1186/1744-8069-8-52
84. Liu H, Peng L, Liu C, et al. Activation of Bombesin Receptor Subtype-3 Promotes Antigen-Presenting Action in Human Bronchial Epithelial Cells. Int Arch Allergy Immunol. 2018;175(1-2):53-60. doi: 10.1159/000485895
85. Helle KB, Metz-Boutigue M-H, Cerra MC, Angelone T. Chromogranins: from discovery to current times. Pflügers Archiv – Eur J Physiol. 2017;470(1):143-54. doi: 10.1007/s00424-017-2027-6
86. Sorhaug S, Langhammer A, Waldum HL, et al. Increased serum levels of chromogranin A in male smokers with airway obstruction. Eur Respir J. 2006;28(3):542-8. doi: 10.1183/09031936.06.00092205
87. Ottesen AH, Carlson CR, Edwards AG, et al. Secretoneurin, a Novel Endogenous CaMKII Inhibitor, Augments Cardiomyocyte Calcium Handling and Inhibits Arrhythmogenic Calcium Release. Biophysical J. 2015;108(2). doi: 10.1016/j.bpj.2014.11.1863
88. Maslyukov PM, Emanuilov AI, Nozdrachev AD. Developmental changes of neurotransmitter properties in sympathetic neurons. Uspekhi gerontologii. 2016;29(3):442–53 (In Russ.) PMID: 28849877
89. Nevzorova VA, Tilik TV, Gilifanov EA. Role of matrix metalloproteinases in forming morphofunctional imbalance of airways in case of chronic obstructive lung disease. Tikhookeanskii med. zhurn. 2011;2:9-13 (In Russ.)
90. Chelluboina B, Nalamolu KR, Klopfenstein JD, et al. MMP-12, a Promising Therapeutic Target for Neurological Diseases. Molecular Neurobiol. 2017;55(2):1405-9. doi: 10.1007/s12035-017-0418-5
91. Xu J, Xu F, Barrett E. Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice. Am J Physiology-Lung Cell Molecular Physiol. 2008;295(1). doi: 10.1152/ajplung. 00282.2007
92. Chaouat A. Pulmonary hypertension in COPD. Respiratory Medicine: COPD Update. 2007;3(1):18-9. doi: 10.1016/s1745-0454(07)70048-5
93. Springer J, Amadesi S, Trevisani M, et al. Effects of alpha calcitonin gene-related peptide in human bronchial smooth muscle and pulmonary artery. Regulatory Peptides. 2004;118(3):127-34. doi: 10.1016/j.regpep.2003.11.006
94. Roos AB, Berg T, Nord M. A Relationship between Epithelial Maturation, Bronchopulmonary Dysplasia, and Chronic Obstructive Pulmonary Disease. Pulmonary Med. 2012;2012:1-10. doi: 10.1155/2012/196194
ФГБОУ ВО «Тихоокеанский государственный медицинский университет» Минздрава России, Владивосток, Россия
________________________________________________
T.A. Brodskaya, V.A. Nevzorova, M.S. Vasileva, V.V. Lavrenyuk
Pacific State Medical University, Vladivostok, Russia