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Functional State of Vascular Endothelium in Patients With Pulmonary Arterial Hypertension Associated With Congenital Heart Diseases

Emel’yanchik E. Yu.1, Vol’f N. G.2, Vesemiller O. A.1, Salmina A. B.1
1Krasnoyarsk State Medical University named after Prof. V.F. Vojno-Yasenetsky, Krasnoyarsk, Russia
2Krasnoyarsk Regional Clinical Center for Maternity and Childhood Protection, Krasnoyarsk, Russia

Keywords: pulmonary arterial hypertension; congenital heart disease;, endothelial dysfunction; vascular endothelial growth factor; membrane blebbing; peripheral blood lymphocytes; soluble platelet/endothelial cell adhesion molecule 1; hypoxia; apoptosis

DOI: 10.18087/cardio.2017.8.10016

In this article, we present results of the study of blebbing activity of membranes of peripheral blood lymphocytes, concentrations of soluble platelet/endothelial cell adhesion molecule 1, and vascular endothelial growth factor (VEGF) in patients with pulmonary arterial hypertension associated with congenital heart diseases. The research has shown that hypoxia and hemodynamic factors are the initiators of blebbing of membrane of peripheral blood lymphocytes. The activity of blebbing increases in parallel with the severity of the disease. Aberrant leukocyte-endothelial interactions lead to the breach of athrombogenic endothelium function, hypercoagulation and risk of thrombosis. Revealed overexpression of VEGF, aimed at restoration of endothelial cells, has been most pronounced in cyanotic congenital heart defects. We suggest that the potentiating effect of apoptosis and endothelial cells’ proliferation is a key factor of irreversibility of pulmonary arterial hypertension in congenital heart defects.
  1. Galie N., Manes A., Branzi A. The endothelin system in pulmonary hypertension. Cardiovascuiar Research 2004;61:227–237.
  2. Benza R.L., Miller D.P., Gomberg-Maitland M. et al. Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation 2010;122:164–172.
  3. Aird W.C. Endothelium in health and disease. Pharmacol Rep 2008;60 (1):139–143.
  4. Amabile N., Guignabert C., Montani D. et al. Cellular microparticles in the pathogenesis of pulmonary hypertension. Eur Respir J 2013;42 (1):272–279. Doi:10.1183/09031936.00087212.
  5. Levy M., Bonnet D., Mauge L. et al. Circulating endothelial cells in refractory pulmonary hypertension in children: markers of treatment efficacy and clinical worsening. Plos One 2013;8:6: e65114. Doi:10.1371/journal.pone.006511484.
  6. Lopes A.A., Flores P.C., Diaz G.F., Mesquita S.M. F. Congenital heart disease and pulmonary arterial hypertension in South America (2013 Grover Conference series) Pulm Circulation 2014;4 (3) 370–377. DOI: 10.1086/676747.
  7. Smadja D.M., Gaussem P., Mauge L. et al. Comparison of endothelial biomarkers according to reversibility of pulmonary hypertension secondary to congenital heart disease. Pediatr Cardiol 2010;31:5:657–662. Doi:10.1007/s00246-010-9674-0.
  8. Colvin K.L., Dufva M.J., Delaney R.P. et al. Biomarkers for Pediatric Pulmonary Arterial Hypertension – A Call to Collaborate. Front Pediatr 2014;2:7. Doi: 10.3389/fped.2014.00007 PMCID: PMC3910125.
  9. Oguz M.M., Oguz A.D., Sanli C. et al. Serum Levels of Soluble ICAM-1 in Children with Pumonary Artery Hypertension. Heart Inst J 2014;41 (2): 159–164. doi: 10.14503/THIJ-2–3012 PMCID: PMC4004489.
  10. El-Melegy N.T., Mohamed N.A. Angiogenic biomarkers in children with congenital heart disease: possible implications. Italian J NT Pediatrics 2010;36 (1):32. DOI: 10.1186/1824-7288-36-32.
  11. Egorova A. B., Uspenskaya Yu. A. Damage to the cytoskeleton and cell membranes in apoptosis Biology Bulletin Reviews 2001;121 (5):502–510. Russian (Егорова А. Б, Успенская Ю. А. Повреждение цитоскелета и клеточных мембран при апоптозе. Успехи современной биологии 2001;121 (5):502–510.)
  12. Manskikh V. N. Morphological methods for verifying and quantifying apoptosis. Bulletin of Siberian Medicine 2004;3 (1):63–70. Russian (Манских В. Н. Морфологические методы верификации и количественной оценки апоптоза. Бюллетень сибирской медицины 2004;3 (1):63–70).
  13. Sata M., Suhara T., Walsh K. Vascular Endothelial Cells and Smooth Muscle Cells Differ in Expression of Fas and FasLand in Sensitivity to FasL Induced Cell Death. Arterioscler Thromb Vasc Biol 2000;20:309–316.
  14. Sakao S., Tatsumi K, Voelkel N.F. Reversible or Irreversible Remodeling in Pulmonary Arterial Hypertension. Am J Respir Cell Mol Biol 2010;43 (6):629–634.
  15. Taraseviciene-Stewart L., Kasahara Y., Alger L. et al. Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death-dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension. FASEB J 2001;15:427–438.
  16. Sakao S., Taraseviciene-Stewart L., Lee J.D. et al. Initial apoptosis is followed by increased proliferation of apoptosis-resistant endothelial cells. FASEB J 2005;19:1178–1180.
  17. Ghofrani H.A., Barst R.J., Benza R.L. et al. Future perspectives for the treatment of pulmonary arterial hypertension. J Am Coll Cardiol 2009;54:108 – S117.
  18. Inzhutova A. I., Larionov A. A., Salmina A. B., Petrova M. M. Molecular and cellular mechanisms of endothelial dysfunction in different pathology (report 1). The Siberian medical journal 2010;96 (5):85–88. Russian (Инжутова А. И., Ларионов А. А., Салмина А. Б., Петрова М. М. Молекулярно-клеточные механизмы эндотелиальной дисфункции различного генеза (сообщение 1). Сибирский медицинский журнал 2010;96 (5):85–88.
  19. Cerro M.J., Abman S., Diaz G. et al. A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: Report from he PVRI Pediatric Taskforce, Panama 2011. Pulm Circ 2011;1 (2):286–298.
  20. Zhang Y., Meng H., Ma R . et al. Сirculating microparticles, blood cells, and endothelium induce procoagulant in sepsis through phosphatidilserine exposure. Shock 2016;45 (3):299–307.
  21. Matsuura Y., Yamashita A., Ivakiri T. et al. Vascular wall hypoxia promotes arterial thrombus formation via augmentation of vascular thrombogenicity. Thrombosis and Haemostasis 2015;114:1:158–172.
  22. Hussein Y., Shehata M. Vascular endothelial growth factor in children with cyanotic and acyanotic congenital heart disease. Arch Med Sci 2010;30 (6) 2: 221–225. doi: 10.5114/aoms.2010.13899
Emel’yanchik E. Yu., Vol’f N. G., Vesemiller O. A., Salmina A. B. Functional State of Vascular Endothelium in Patients With Pulmonary Arterial Hypertension Associated With Congenital Heart Diseases. Kardiologiia. 2017;57(8):40–46.

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