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VEGF-C — a biomarker of renal injury in the experimental model of intra-abdominal hypertension

https://doi.org/10.47093/2218-7332.2020.11.3.47-56

Abstract

Lymphangiogenesis plays an important role in development of renal parenchyma inflammation during kidney injury. Vascular endothelial growth factor type C (VEGF-C), cytokine that regulates lymphangiogenesis, is a potential early biomarker for acute kidney injury.
Aim. To study the concentration of VEGF-C in renal homogenate and blood serum of newborn rats with experimental intraabdominal hypertension (IAH) of varying severity and duration, to establish a relationship with morphological changes in the renal tissue.
Materials and methods. The experiment was conducted on 50 newborn Wistar rats. Rats were divided into 5 groups of 10 rats each: groups 1 and 2 with mild IAH lasting 5 and 10 days, respectively, and groups 3 and 4 with severe IAH lasting 5 and 10 days, respectively, and the control group. IAH was modelled by injecting sterile vaseline into the abdominal cavity to a predetermined level of IAH under the control of intra-vesical manometry. VEGF-C content was measured by ELISA. Morphological examination of the biopsy material and its photography were carried out using a Leica DM2000 microscope. The Mann—Whitney, Kruskal—Wallis, Wilcoxon tests, as well as one-way ANOVA, were used for statistical analysis.
Results. The level of VEGF-C in the renal homogenate was increased in all groups (pc < 0.001); the degree of VEGF-C increase depended on the severity of IAH (p < 0.05) but not on the duration of IAH exposure. The VEGF-C blood serum level was increased only in group 3 (pc = 0.011). Morphological analysis showed hydropic dystrophy: changes in the height of the tubular epithelium, an increase in interstitial edema, expansion of the urinary spaces of glomeruli. The degree of morphological changes depended on the severity and duration of IAH.
Conclusion. Changes in VEGF-C level assessed in the renal homogenate correlated with morphological changes in renal tissue of rats with different severity and duration of IAH.

About the Authors

V. V. Iakovlev
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Vladislav V. Iakovlev, Postgraduate, Pathophysiology Department

8/2, Trubetskaya str., Moscow, 119991

8 (926) 761-20-68



A. V. Badaeva
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Anastasiia V. Badaeva, student

8/2, Trubetskaya str., Moscow, 119991



E. I. Ivanova
Petrovsky National Research Centre of Surgery
Russian Federation

Elena I. Ivanova, pathologist

2, Abrikosovsky lane, GSP-1, Moscow, 119991



L. O. Severgina
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Lyubov O. Severgina, Dr. of Sci. (Medicine), pathologist, Professor, Department of Pathological Anatomy named after A.I. Strukov

8/2, Trubetskaya str., Moscow, 119991



L. D. Maltseva
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Larisa D. Maltseva, Cand. of Sci. (Medicine), Associate Professor, Pathophysiology Department

8/2, Trubetskaya str., Moscow, 119991



O. L. Morozova
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Olga L. Morozova, Dr. of Sci. (Medicine), Professor, Pathophysiology Department

8/2, Trubetskaya str., Moscow, 119991



References

1. Rauniyar K, Jha SK, Jeltsch M. Biology of Vascular Endothelial Growth Factor C in the Morphogenesis of Lymphatic Vessels. Front Bioeng Biotechnol 2018;6. DOI:10.3389/fbioe.2018.00007.

2. Veikkola T, Jussila L, Makinen T, Karpanen T, Jeltsch M, Petrova TV, et al. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. EMBO J 2001;20:1223–31. DOI:10.1093/emboj/20.6.1223.

3. Mäkinen T, Veikkola T, Mustjoki S, Karpanen T, Catimel B, Nice EC, et al. Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3. EMBO J 2001;20:4762–73. DOI:10.1093/emboj/20.17.4762.

4. Huggenberger R, Ullmann S, Proulx ST, Pytowski B, Alitalo K, Detmar M. Stimulation of lymphangiogenesis via VEGFR-3 inhibits chronic skin inflammation. J Exp Med 2010;207:2255–69. DOI:10.1084/jem.20100559.

5. Hamada K, Oike Y, Takakura N, Ito Y, Jussila L, Dumont DJ, et al. VEGF-C signaling pathways through VEGFR-2 and VEGFR-3 in vasculoangiogenesis and hematopoiesis. Blood 2000;96:3793–800. DOI:10.1182/blood.V96.12.3793.

6. Kim H, Kataru RP, Koh GY. Inflammation-associated lymphangiogenesis: a double-edged sword? J Clin Invest 2014;124:936–42. DOI:10.1172/JCI71607.

7. Onimaru M, Yonemitsu Y, Fujii T, Tanii M, Nakano T, Nakagawa K, et al. VEGF-C regulates lymphangiogenesis and capillary stability by regulation of PDGF-B. Am J Physiol Heart Circ Physiol 2009;297:H1685-1696. DOI:10.1152/ajpheart.00015.2009.

8. Lee AS, Lee JE, Jung YJ, et al. Vascular endothelial growth factor-C and -D are involved in lymphangiogenesis in mouse unilateral ureteral obstruction. Kidney Int. 2013;83:50-62. Kidney Int 2017;92:1018. DOI:10.1016/j.kint.2017.07.006.

9. Hasegawa S, Nakano T, Torisu K, Tsuchimoto A, Eriguchi M, Haruyama N, et al. Vascular endothelial growth factor-C ameliorates renal interstitial fibrosis through lymphangiogenesis in mouse unilateral ureteral obstruction. Lab Invest 2017;97:1439–52. DOI:10.1038/labinvest.2017.77.

10. Chang X, Yang Q, Zhang C, Zhang Y, Liang X, Liu Y, et al. Roles for VEGF-C/NRP-2 axis in regulating renal tubular epithelial cell survival and autophagy during serum deprivation. Cell Biochem Funct 2019;37:290–300. DOI:10.1002/cbf.3402.

11. Zarjou A, Black LM, Bolisetty S, Traylor AM, Bowhay SA, Zhang M-Z, et al. Dynamic signature of lymphangiogenesis during AKI and CKD. Lab Invest 2019;99:1376–88. DOI:10.1038/s41374-019-0259-0.

12. Kirkpatrick AW, Roberts DJ, De Waele J, Jaeschke R, Malbrain MLNG, De Keulenaer B, et al. Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome. Intensive Care Med 2013;39:1190–206. DOI:10.1007/s00134-013-2906-z.

13. Thabet FC, Bougmiza IM, Chehab MS, Bafaqih HA, AlMohaimeed SA, Malbrain MLNG. Incidence, Risk Factors, and Prognosis of Intra-Abdominal Hypertension in Critically Ill Children: A Prospective Epidemiological Study. J Intensive Care Med 2016;31:403–8. DOI:10.1177/0885066615583645.

14. Steinau G, Kaussen T, Bolten B, Schachtrupp A, Neumann UP, Conze J, et al. Abdominal compartment syndrome in childhood: diagnostics, therapy and survival rate. Pediatric Surgery International 2011;27:399–405. DOI:10.1007/s00383-010-2808-x.

15. Kaussen T, Steinau G, Srinivasan P, Otto J, Sasse M, Staudt F, et al. Recognition and management of abdominal compartment syndrome among German pediatric intensivists: results of a national survey. Annals of Intensive Care 2012;2:S8. DOI:10.1186/2110-5820-2-S1-S8.

16. Vidal MG, Ruiz Weisser J, Gonzalez F, Toro MA, Loudet C, Balasini C, et al. Incidence and clinical effects of intra-abdominal hypertension in critically ill patients. Crit Care Med 2008;36:1823–31. DOI:10.1097/CCM.0b013e31817c7a4d.

17. De Waele J, Desender L, De Laet I, Ceelen W, Pattyn P, Hoste E. Abdominal decompression for abdominal compartment syndrome in critically ill patients: a retrospective study. Acta Clin Belg 2010;65:399–403. DOI:10.1179/acb.2010.65.6.005.

18. Carr JA. Abdominal compartment syndrome: a decade of progress. J Am Coll Surg 2013;216:135–46. DOI:10.1016/j.jamcollsurg.2012.09.004.

19. Ejike JC, Humbert S, Bahjri K, Mathur M. Outcomes of children with abdominal compartment syndrome. Acta Clin Belg 2007;62 Suppl 1:141–8. DOI:10.1179/acb.2007.62.s1.018.

20. Pearson EG, Rollins MD, Vogler SA, Mills MK, Lehman EL, Jacques E, et al. Decompressive laparotomy for abdominal compartment syndrome in children: before it is too late. J Pediatr Surg 2010;45:1324–9. DOI:10.1016/j.jpedsurg.2010.02.107.

21. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington (DC): National Academies Press (US); 2011. ISBN: 978-0-309-15401-7.

22. Kinashi H, Falke LL, Nguyen TQ, Bovenschen N, Aten J, Leask A, et al. Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis. Kidney Int 2017;92:850–63. DOI:10.1016/j.kint.2017.03.029.

23. Beaini S, Saliba Y, Hajal J, Smayra V, Bakhos J-J, Joubran N, et al. VEGF-C attenuates renal damage in salt-sensitive hypertension. J Cell Physiol 2019;234:9616–30. DOI:10.1002/jcp.27648.

24. Joory KD, Levick JR, Mortimer PS, Bates DO. Vascular endothelial growth factor-C (VEGF-C) expression in normal human tissues. Lymphat Res Biol 2006;4:73–82. DOI:10.1089/lrb.2006.4.73.

25. Divarci E, Karapinar B, Yalaz M, Ergun O, Celik A. Incidence and prognosis of intraabdominal hypertension and abdominal compartment syndrome in children. J Pediatr Surg 2016;51:503–7. DOI:10.1016/j.jpedsurg.2014.03.014.

26. Villa G, Samoni S, De Rosa S, Ronco C. The Pathophysiological Hypothesis of Kidney Damage during Intra-Abdominal Hypertension. Front Physiol 2016;7. DOI:10.3389/fphys.2016.00055.

27. Köşüm A, Borazan E, Maralcan G, Aytekin A. Biochemical and histopathological changes of intra-abdominal hypertension on the kidneys: Experimental study in rats. Ulus Cerrahi Derg 2013;29:49–53. DOI:10.5152/UCD.2013.39.

28. Chang Y, Qi X, Li Z, Wang F, Wang S, Zhang Z, et al. Hepatorenal syndrome: insights into the mechanisms of intra-abdominal hypertension. Int J Clin Exp Pathol 2013;6:2523–8.

29. Morozov D, Morozova O, Pervouchine D, Severgina L, Tsyplakov A, Zakharova N, et al. Hypoxic renal injury in newborns with abdominal compartment syndrome (clinical and experimental study). Pediatr Res 2018;83:520–6. DOI:10.1038/pr.2017.263.


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