Differential Gene Expression in the Lungs of Rats with Experimental Chronic Thromboembolic Pulmonary Hypertension

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Chronic thromboembolic pulmonary hypertension (CTEPH) remains a severe disease with low survival rates in inoperable patients, despite advances in treatment. The molecular mechanisms underlying CTEPH pathogenesis are not fully understood, necessitating further research to identify new therapeutic targets. Although numerous animal models of CTEPH have been developed, demonstrating their clinical relevance requires establishing molecular bioequivalence with human pathophysiological processes, particularly through matching gene expression profiles. To analyze differential gene expression in rat lung tissues following CTEPH modeling using alginate microsphere administration and to assess the applicability of this model for developing and studying new therapeutic strategies for CTEPH. CTEPH was modeled in Wistar rats via repeated intravenous injections of biodegradable alginate microspheres. The transcriptional profile of lung tissue samples collected from CTEPH rats at 2 weeks, 6 weeks, and control rats was analyzed using high-throughput RNA sequencing. Differentially expressed genes (DEGs) were identified using DESeq2. Gene expression changes were validated by reverse transcription PCR (RT-PCR). Transcriptomic analysis revealed that CTEPH modeling at 2 weeks upregulated genes associated with inflammation, whereas at 6 weeks, downregulation of extracellular matrix-related genes was observed. Transcription factor analysis showed predominant regulation of DEG promoters by C2H2 zinc finger proteins Zfp278 and KIF5, suggesting their involvement in the cellular response during CTEPH development. RT-PCR validation of Cav1, Eng, vWF, and Gja5 expression in a larger set of lung tissue samples confirmed the dynamic changes detected in the transcriptomic analysis. This study identified dynamic transcriptional changes during CTEPH development in rats, including dysregulation of extracellular matrix, inflammation, and endothelial dysfunction-related genes, consistent with current understanding of CTEPH pathogenesis. The findings demonstrate that the developed rat model exhibits transcriptional profile alterations comparable to those observed in human CTEPH, supporting its relevance for preclinical research.

Sobre autores

N. Vachrushev

Almazov National Medical Research Centre

Email: drabrikos@gmail.com
Saint-Petersburg, Russia

L. Shilenko

Almazov National Medical Research Centre

Saint-Petersburg, Russia

A. Karpov

Almazov National Medical Research Centre; Saint Petersburg State Chemical and Pharmaceutical University

Saint-Petersburg, Russia; Saint-Petersburg, Russia

D. Ivkin

Saint Petersburg State Chemical and Pharmaceutical University

Saint-Petersburg, Russia

M. Galagudza

Almazov National Medical Research Centre

Saint-Petersburg, Russia

A. Kostareva

Almazov National Medical Research Centre

Saint-Petersburg, Russia

O. Kalinina

Almazov National Medical Research Centre; Saint-Petersburg Pasteur Institute

Saint-Petersburg, Russia

Bibliografia

  1. Avdeev SN, Barbarash OL, Valieva ZS, Volkov AV, Veselova TN, Galyavich AS, Goncharova NS, Gorbachevsky SY, Gramovich VY, Danilov NM, Klimenko AA, Martynyuk TY, Moiseeva OM, Ryzhkova DV, Simakova MA, Sinitsyn VE, Stukalova OV, Chazova IE, Chernogrivov IE, Shmalts AA, Tsareva NA (2024) Clinical practice guidelines for Pulmonary hypertension, including chronic thromboembolic pulmonary hypertension. Russ J Cardiol 29: 6161. https://doi.org/10.15829/1560-4071-2024-6161
  2. Otani N, Watanabe R, Tomoe T, Toyoda S, Yasu T, Nakamoto T (2023) Pathophysiology and Treatment of Chronic Thromboembolic Pulmonary Hypertension. Int J Mol Sci 24: 3979. https://doi.org/10.3390/ijms24043979
  3. Kim NH, Delcroix M, Jais X, Madani MM, Matsubara H, Mayer E, Ogo T, Tapson VF, Ghofrani H-A, Jenkins DP (2019) Chronic thromboembolic pulmonary hypertension. Eur Respir J 53: 1801915. https://doi.org/10.1183/13993003.01915-2018
  4. Coquoz N, Weilenmann D, Stolz D, Popov V, Azzola A, Fellrath J-M, Stricker H, Pagnamenta A, Ott S, Ulrich S, Gyorik S, Pasquier J, Aubert J-D (2018) Multicentre observational screening survey for the detection of CTEPH following pulmonary embolism. Eur Respir J 51: 1702505. https://doi.org/10.1183/13993003.02505-2017
  5. Ogawa A, Satoh T, Fukuda T, Sugimura K, Fukumoto Y, Emoto N, Yamada N, Yao A, Ando M, Ogino H, Tanabe N, Tsujino I, Hanaoka M, Minatoya K, Ito H, Matsubara H (2017) Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension: Results of a Multicenter Registry. Circ Cardiovasc Qual Outcomes 10: e004029. https://doi.org/10.1161/CIRCOUTCOMES.117.004029
  6. Klok FA, Couturand F, Delcroix M, Humbert M (2020) Diagnosis of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Eur Respir J 55: 2000189. https://doi.org/10.1183/13993003.00189-2020
  7. Bonderman D, Jakowitsch J, Adlbrecht C, Schemper M, Kyrie P, Schönauer V, Exner M, Klepeiko W, Kneussl M, Maurer G, Lang I (2005) Medical conditions increasing the risk of chronic thromboembolic pulmonary hypertension. Thromb Haemost 93: 512–516. https://doi.org/10.1160/TH04-10-0657
  8. Pengo V, Lensing AWA, Prins MH, Marchiori A, Davidson BL, Tiozzo F, Albanese P, Biasiolo A, Pegoraro C, Iliceto S, Prandoni P (2004) Incidence of Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Embolism. N Engl J Med 350: 2257–2264. https://doi.org/10.1056/NEJMoa032274
  9. Simonneau G, Dorfmüller P, Guignabert C, Mercier O, Humbert M (2022) Chronic thromboembolic pulmonary hypertension: the magic of pathophysiology. Ann Cardiothorac Surg 11: 106–119. https://doi.org/10.21037/acs-2021-pte-10
  10. Vrigkou E, Tsantes A, Konstantonis D, Rapti E, Maratou E, Pappas A, Halvatsiotis P, Tsangaris I (2022) Platelet, Fibrinolytic and Other Coagulation Abnormalities in Newly-Diagnosed Patients with Chronic Thromboembolic Pulmonary Hypertension. Diagnostics 12: 1238. https://doi.org/10.3390/diagnostics12051238
  11. Moser KM, Bloor CM (1993) Pulmonary Vascular Lesions Occurring in Patients with Chronic Major Vessel Thromboembolic Pulmonary Hypertension. Chest 103: 685–692. https://doi.org/10.1378/chest.103.3.685
  12. Simonneau G, Torbicki A, Dorfmüller P, Kim N (2017) The pathophysiology of chronic thromboembolic pulmonary hypertension. Eur Respir Rev 26: 160112. https://doi.org/10.1183/16000617.0112-2016
  13. Rahaghi FN, Ross JC, Agarwal M, Gonzalez G, Come CE, Diaz AA, Vegas-Sánchez-Ferrero G, Hunsaker A, Estépar RSJ, Waxman AB, Washko GR (2016) Pulmonary Vascular Morphology as an Imaging Biomarker in Chronic Thromboembolic Pulmonary Hypertension. Pulm Circ 6: 70–81. https://doi.org/10.1086/685081
  14. Oliveira T, Kato-Morinaga L, Assad A, Oliveira E, Jardim C, Alves-Jr J, Souza R, Fernandes CJC (2019) Platelets and chronic thromboembolic pulmonary hypertension. In: Pulmonary hypertension. Eur Respiratory Society. PA1444.
  15. Perino MG, Moldobaeva A, Jenkins J, Wagner EM (2013) Chemokine Localization in Bronchial Angiogenesis. PLoS One 8: e66432. https://doi.org/10.1371/journal.pone.0066432
  16. Miao R, Wang Y, Wan J, Leng D, Gong J, Li J, Liang Y, Zhai Z, Yang Y (2017) Microarray expression profile of circular RNAs in chronic thromboembolic pulmonary hypertension. Medicine (Baltimore) 96: e7354. https://doi.org/10.1097/MD.0000000000007354
  17. Guo L, Yang Y, Liu J, Wang L, Li J, Wang Y, Liu Y, Gu S, Gan H, Cai J, Yuan JX-J, Wang J, Wang C (2014) Differentially Expressed Plasma MicroRNAs and the Potential Regulatory Function of Let-7b in Chronic Thromboembolic Pulmonary Hypertension. PLoS One 9: e101055. https://doi.org/10.1371/journal.pone.0101055
  18. Miao R, Dong X, Gong J, Li Y, Guo X, Wang J, Huang Q, Wang Y, Li J, Yang S, Kuang T, Liu M, Wan J, Zhai Z, Zhong J, Yang Y (2022) Single-cell RNA-sequencing and microarray analyses to explore the pathological mechanisms of chronic thromboembolic pulmonary hypertension. Front Cardiovasc Med 9: 900353. https://doi.org/10.3389/fcvm.2022.900353
  19. Gu S, Li G, Zhang X, Yan J, Gao J, An X, Liu Y, Su P (2015) Aberrant expression of long noncoding RNAs in chronic thromboembolic pulmonary hypertension. Mol Med Rep 11: 2631–2643. https://doi.org/10.3892/mmr.2014.3102
  20. Gu S, Su P, Yan J, Zhang X, An X, Gao J, Xin R, Liu Y (2014) Comparison of gene expression profiles and related pathways in chronic thromboembolic pulmonary hypertension. Int J Mol Med 33: 277–300. https://doi.org/10.3892/ijmm.2013.1582
  21. Wang Y-C, Cui X-B, Chuang Y-H, Chen S-Y (2017) Janus Kinase 3, a Novel Regulator for Smooth Muscle Proliferation and Vascular Remodeling. Arterioscler Thromb Vasc Biol 37: 1352–1360. https://doi.org/10.1161/ATVBAHA.116.308895
  22. Lee C, Viswanathan G, Choi I, Jassal C, Kohlmann T, Rajagopal S (2020) Beta-Arrestins and Receptor Signaling in the Vascular Endothelium. Biomolecules 11: 9. https://doi.org/10.3390/biom11010009
  23. Xu W, Deng M, Meng X, Sun X, Tao X, Wang D, Zhang S, Zhen Y, Liu X, Liu M (2022) The alterations in molecular markers and signaling pathways in chronic thromboembolic pulmonary hypertension, a study with transcriptome sequencing and bioinformatic analysis. Front Cardiovasc Med 9: 961305. https://doi.org/10.3389/fcvm.2022.961305
  24. Viswanathan G, Kirshner HF, Nazo N, Ali S, Ganapathi A, Cumming I, Zhuang Y, Choi I, Warman A, Jassal C, Almeida-Peters S, Haney J, Corcoran D, Yu Y-R, Rajagopal S (2023) Single-Cell Analysis Reveals Distinct Immune and Smooth Muscle Cell Populations that Contribute to Chronic Thromboembolic Pulmonary Hypertension. Am J Respir Crit Care Med 207: 1358–1375. https://doi.org/10.1164/rccm.202203-0441OC
  25. Karpov AA, Vaulina DD, Smirnov SS, Moiseeva OM, Galagudza MM (2022) Rodent models of pulmonary embolism and chronic thromboembolic pulmonary hypertension. Heliyon 8: e09014. https://doi.org/10.1016/j.heliyon.2022.e09014
  26. Mercier O, Fadel E (2013) Chronic thromboembolic pulmonary hypertension: animal models. Eur Respir J 41: 1200–1206. https://doi.org/10.1183/09031936.00101612
  27. Karpov AA, Vachrushev NS, Shilenko LA, Smirnov SS, Bunenkov NS, Butskih MG, Chervaev A-KA, Vaulina DD, Ivkin DYu, Moiseeva OM, Galagudza MM (2023) Sympathetic Denervation and Pharmacological Stimulation of Parasympathetic Nervous System Prevent Pulmonary Vascular Bed Remodeling in Rat Model of Chronic Thromboembolic Pulmonary Hypertension. J Cardiovasc Dev Dis 10: 40. https://doi.org/10.3390/jcdd10020040
  28. Karpov AA, Anikin NA, Mihailova AM, Smirnov SS, Vaulina DD, Shilenko LA, Ivkin DYu, Bagrov AY, Moiseeva OM, Galagudza MM (2021) Model of Chronic Thromboembolic Pulmonary Hypertension in Rats Caused by Repeated Intravenous Administration of Partially Biodegradable Sodium Alginate Microspheres. Int J Mol Sci 22: 1149. https://doi.org/10.3390/ijms22031149
  29. Vachrushev N S, Karpov AA, Shilenko LA, Vaulina DD, Kalinina OV, Kostareva AA, Galagudza MM (2025) Lung tissue RNA sequencing shows dysregulation of the bronchial epithelium in a rat model of chronic thromboembolic pulmonary hypertension. Bull Exp Biol Med 179: 668–771. https://doi.org/10.47056/0365-9615-2025-179-6-668-671
  30. Ewels PA, Peltzer A, Fillinger S, Patel H, Alneberg J, Wilm A, Garcia MU, Di Tommaso P, Nahnsen S (2020) The nf-core framework for community-curated bioinformatics pipelines. Nat Biotechnol 38: 276–278. https://doi.org/10.1038/s41587-020-0439-x
  31. Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15: 550. https://doi.org/10.1186/s13059-014-0550-8
  32. Kucukoglu MS (2019) Ten Year Outcome of Chronic Thromboembolic Pulmonary Hypertension Patients in a Tertiary University Hospital. Anatol J Cardiol 23(2): 105–109. https://doi.org/10.14744/AnatolJCardiol.2019.90329
  33. Xiao G, Zhuang W, Wang T, Lian G, Luo L, Ye C, Wang H, Xie L (2020) Transcriptomic analysis identifies Toll-like and Nod-like pathways and necroptosis in pulmonary arterial hypertension. J Cell Mol Med 24: 11409–11421. https://doi.org/10.1111/jcmm.15745
  34. Wu D, Chen Y, Wang W, Li H, Yang M, Ding H, Lv X, Lian N, Zhao J, Deng C (2020) The role of inflammation in a rat model of chronic thromboembolic pulmonary hypertension induced by carrageenan. Ann Transl Med 8: 492–492. https://doi.org/10.21037/atm.2020.02.86
  35. Quarck R, Wynants M, Verbeken E, Meyns B, Delcroix M (2015) Contribution of inflammation and impaired angiogenesis to the pathobiology of chronic thromboembolic pulmonary hypertension. Eur Respir J 46: 431–443. https://doi.org/10.1183/09031936.00009914
  36. Yang M, Deng C, Wu D, Zhong Z, Lv X, Huang Z, Lian N, Liu K, Zhang Q (2016) The role of mononuclear cell tissue factor and inflammatory cytokines in patients with chronic thromboembolic pulmonary hypertension. J Thromb Thrombolys 42: 38–45. https://doi.org/10.1007/s11239-015-1323-2
  37. Cisowska-Czajka ME, Mazij MP, Kotschy MH, Lewczuk J (2016) Plasma concentrations of tissue factor and its inhibitor in chronic thromboembolic pulmonary hypertension: a step closer to explanation of the disease aetiology? Kardiol Pol 74: 1332–1338. https://doi.org/10.5603/KPa2016.0088
  38. Kimura H, Okada O, Tanabe N, Tanaka Y, Terai M, Takiguchi Y, Masuda M, Nakajima N, Hiroshima K, Inadera H, Matsushima K, Kuriyama T (2001) Plasma Monocyte Chemoattractant Protein-1 and Pulmonary Vascular Resistance in Chronic Thromboembolic Pulmonary Hypertension. Am J Respir Crit Care Med 164: 319–324. https://doi.org/10.1164/ajrccm.164.2.2006154
  39. Hoffmann-Yold A, Hesselstrand R, Fretheim H, Ueland T, Andreassen AK, Brunborg C, Palchevskiy V, Midtvedt Ø, Garen T, Aukrust P, Belperio JA, Molberg Ø (2018) CCL21 as a Potential Serum Biomarker for Pulmonary Arterial Hypertension in Systemic Sclerosis. Arthritis Rheumatol 70: 1644–1653. https://doi.org/10.1002/art.40534
  40. Amsellem V, Abid S, Poupel L, Parpaleix A, Rodero M, Gary-Bobo G, Latiri M, Dubois-Rande J-L, Lipskaia L, Combadiere C, Adnot S (2017) Roles for the CX3CL1/CX3CR1 and CCL2/CCR2 Chemokine Systems in Hypoxic Pulmonary Hypertension. Am J Respir Cell Mol Biol 56: 597–608. https://doi.org/10.1165/rcmb.2016-0201OC
  41. Nie X, Tan J, Dai Y, Liu Y, Zou J, Sun J, Ye S, Shen C, Fan L, Chen J, Bian J-S (2018) CCL5 deficiency rescues pulmonary vascular dysfunction, and reverses pulmonary hypertension via caveolin-1-dependent BMPR2 activation. J Mol Cell Cardiol 116: 41–56. https://doi.org/10.1016/j.yjmcc.2018.01.016
  42. Bordenave J, Thuillet R, Tu L, Phan C, Cumont A, Marsol C, Huertas A, Savale L, Hibert M, Galzi J-L, Bonnet D, Humbert M, Frossard N, Guignabert C (2020) Neutralization of CXCL12 attenuates established pulmonary hypertension in rats. Cardiovasc Res 116: 686–697. https://doi.org/10.1093/cvr/cvz153
  43. Drouin M, Saenz J, Chiffoleau E (2020) C-Type Lectin-Like Receptors: Head or Tail in Cell Death Immunity. Front Immunol 11: 251. https://doi.org/10.3389/fimmu.2020.00251
  44. Brown GD, Willment JA, Whitehead L (2018) C-type lectins in immunity and homeostasis. Nat Rev Immunol 18: 374–389. https://doi.org/10.1038/s41577-018-0004-8
  45. Chen Y, Wu C, Wang X, Zhou X, Kang K, Cao Z, Yang Y, Zhong Y, Xiao G (2022) Weighted gene co-expression network analysis identifies dysregulated B-cell receptor signaling pathway and novel genes in pulmonary arterial hypertension. Front Cardiovasc Med 9: 909399. https://doi.org/10.3389/fcvm.2022.909399
  46. Xiao G, Wang T, Zhuang W, Ye C, Luo L, Wang H, Lian G, Xie L (2020) RNA sequencing analysis of monocrotaline-induced PAH reveals dysregulated chemokine and neuroactive ligand receptor pathways. Aging 12: 4953–4969. https://doi.org/10.18632/aging.102922
  47. Keskin N, Deniz E, Eryilmaz J, Un M, Batur T, Ersahin T, Cetin Atalay R, Sakaguchi S, Ellmeier W, Erman B (2015) PATZ1 Is a DNA Damage-Responsive Transcription Factor That Inhibits p53 Function. Mol Cell Biol 35: 1741–1753. https://doi.org/10.1128/MCB.01475-14
  48. Wakasugi T, Shimizu I, Yoshida Y, Hayashi Y, Ikegami R, Suda M, Katsuumi G, Nakao M, Hoyano M, Kashimura T, Nakamura K, Ito H, Nojiri T, Soga T, Minamino T (2019) Role of smooth muscle cell p53 in pulmonary arterial hypertension. PLOS One 14: e0212889. https://doi.org/10.1371/journal.pone.0212889
  49. Li X, He Y, Xu Y, Huang X, Liu J, Xie M, Liu X (2016) KLF5 mediates vascular remodeling via HIF-1α in hypoxic pulmonary hypertension. Am J Physiol-Lung Cell Mol Physiol 310: L299–L310. https://doi.org/10.1152/ajplung.00189.2015
  50. Xie L, Xue X, Taylor M, Ramakrishnan SK, Nagaoka K, Hao C, Gonzalez FJ, Shah YM (2014) Hypoxia-Inducible Factor/MAZ-Dependent Induction of Caveolin-1 Regulates Colon Permeability through Suppression of Occludin, Leading to Hypoxia-Induced Inflammation. Mol Cell Biol 34: 3013–3023. https://doi.org/10.1128/MCB.00324-14
  51. Sánchez-Elsner T, Botella LM, Velasco B, Langa C, Bernabéu C (2002) Endoglin Expression Is Regulated by Transcriptional Cooperation between the Hypoxia and Transforming Growth Factor-β Pathways. J Biol Chem 277: 43799–43808. https://doi.org/10.1074/jbc.M207160200
  52. Whitmarsh AJ, Davis RJ (2000) Regulation of transcription factor function by phosphorylation. Cell Mol Life Sci CMLS 57: 1172–1183. https://doi.org/10.1007/pI0000757
  53. Chettimada S (2015) Caveolae, caveolin-1 and cavin-1: Emerging roles in pulmonary hypertension. World J Respirol 5: 126. https://doi.org/10.5320/wjr.v5.i2.126
  54. Opitz I, Kirschner M (2019) Molecular Research in Chronic Thromboembolic Pulmonary Hypertension. Int J Mol Sci 20: 784. https://doi.org/10.3390/ijms20030784
  55. Zabini D, Nagaraj C, Stacher E, Lang IM, Nierlich P, Klepeiko W, Heinemann A, Olschewski H, Bálint Z, Olschewski A (2012) Angiostatic Factors in the Pulmonary Endarterectomy Material from Chronic Thromboembolic Pulmonary Hypertension Patients Cause Endothelial Dysfunction. PLoS One 7: e43793. https://doi.org/10.1371/journal.pone.0043793
  56. Quarck R, Wynants M, Ronisz A, Sepulveda MR, Wuytack F, Van Raemdonck D, Meyns B, Delcroix M (2012) Characterization of proximal pulmonary arterial cells from chronic thromboembolic pulmonary hypertension patients. Respir Res 13: 27. https://doi.org/10.1186/1465-9921-13-27
  57. Manz XD, Pan X, Symersky P, Majolée J, Hordijk P, Voorberg J, Aman J, Bogaard HJ, Szulcek R (2020) Elevated Von Willebrand Factor expression in the activated pulmonary endothelium of chronic thromboembolic pulmonary hypertension patients enhances platelet adhesion. In: Pulmonary hypertension. European Respiratory Society. 1551.
  58. Halliday SJ, Matthews DT, Talati MH, Austin ED, Su YR, Absi TS, Fortune NL, Gailani D, Matafonov A, West JD, Hemnes AR (2020) A multifaceted investigation into molecular associations of chronic thromboembolic pulmonary hypertension pathogenesis. JRSM Cardiovasc Dis 9: 204800402090699. https://doi.org/10.1177/2048004020906994
  59. Nakala SB, Tura-Ceide O, Aldini G, Smolders VFED, Blanco I, Peinado VI, Castellà M, Barberà JA, Altomare A, Baron G, Carini M, Cascante M, D’Amato A (2021) Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension. Sci Rep 11: 5583. https://doi.org/10.1038/s41598-021-85004-z
  60. Si R, Zhang Q, Cabrera JTO, Zheng Q, Tsuji-Hosokawa A, Watanabe M, Hosokawa S, Xiong M, Jain PP, Ashton AW, Yuan JX -J., Wang J, Makino A (2020) Chronic Hypoxia Decreases Endothelial Connexin 40, Attenuates Endothelium-Dependent Hyperpolarization-Mediated Relaxation in Small Distal Pulmonary Arteries, and Leads to Pulmonary Hypertension. J Am Heart Assoc 9: e018327. https://doi.org/10.1161/JAHA.120.018327
  61. Ten Dijke P, Goumans M-J, Pardali E (2008) Endoglin in angiogenesis and vascular diseases. Angiogenesis 11: 79–89. https://doi.org/10.1007/s10456-008-9101-9

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