Could HIF-1∝ be a novel biomarker for the clinical course and treatment of pulmonary embolism?

Background/aim: Pulmonary embolism PE is associated with high morbidity and mortality rates if not diagnosed and treated rapidly. The aim of our study was to investigate the relationship between levels of hypoxia-induced factor-1 alpha HIF-1∝ and clinical course and prognosis in patients with intermediate low-risk, intermediate high-risk, and high-risk PE. Materials and methods: The study included 240 subjects in 4 groups: a healthy control group n = 60, mean age = 60 ± 15.2, female/male = 30/30 , intermediate low-risk PE group n = 60, mean age = 60 ± 12,5, female/male = 27/33 , intermediate high-risk PE group n = 60, mean age = 61,4 ± 14,8, female/male = 36/24 , and high-risk PE group n = 60, mean age = 62,3 ± 15, female/male = 33/27 . Plasma HIF-1∝ levels were measured using commercial enzyme-linked immunosorbent assay ELISA kit. Results: Comparison of HIF-1∝ levels revealed a statistically significant difference between the groups in proportion to clinical scoring P = 0.001 for all . Comparison of initial HIF-1∝ and troponin levels in intermediate high-risk PE patients given thrombolytic therapy and those treated with enoxaparin sodium showed that HIF-1∝ levels were significantly higher in the group that received thrombolytic therapy P = 0.001 , while there was no difference in troponin levels P = 0.146 . Conclusion: HIF-1∝ can be used in the PE clinical risk stratification and monitoring of PE and may also serve as a valuable early indicator in intermediate high-risk PE, for which early reperfusion therapy is important.

___

  • 1. Bauersachs RM. Clinical presentation of deep vein thrombosis and pulmonary embolism. Best Practice & Research Clinical Haematology 2012; 25 (3) : 243-251. doi: 10.1016/j. beha.2012.07.004
  • 2. Johansson M, Johansson L, Lind M. Incidence of venous thromboembolism in northern Sweden (VEINS): a population-based study. Thrombosis Journal 2014; 12 (1): 6. doi: 10.1186/1477-9560-12-6
  • 3. Samaranayake CB, Royle G, Jackson S, Yap E. Right ventricular dysfunction and pulmonary hypertension following sub‐ massive pulmonary embolism. The Clinical Respiratory Journal 2017; 11 (6): 867-874. doi: 10.1111/crj.12429
  • 4. Tsuzuki Y, Fukumura D, Oosthuyse B, Koike C, Carmeliet P et al. Vascular endothelial growth factor (VEGF) modulation by targeting hypoxia-inducible factor-1α→ hypoxia response element→ VEGF cascade differentially regulates vascular response and growth rate in tumors. Cancer Research 2000; 60 (22): 6248-6252.
  • 5. Wang Y, Zheng G, Meng X, Wang B. The effects of VEGF on deep venous thrombosis in the perioperative period of elderly fracture patients. Pakistan Journal of Pharmaceutical Sciences 2018; 31 (6 (Special)): 2799-2803.
  • 6. Chun Y-S, Yeo E-J, Choi E, Teng C-M, Bae J-M et al. Inhibitory effect of YC-1 on the hypoxic induction of erythropoietin and vascular endothelial growth factor in Hep3B cells. Biochemical Pharmacology 2001; 61 (8): 947-954. doi: 10.1016/S0006- 2952(01)00564-0
  • 7. Semenza GL. HIF-1 and mechanisms of hypoxia sensing. Current Opinion in Cell Biology. 2001; 13 (2): 167-171. doi: 10.1016/S0955-0674(00)00194-0
  • 8. Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. The Lancet 2012; 379 (9828): 1835-1846. doi: 10.1016/S0140-6736(11)61904-1
  • 9. Sekhri V, Mehta N, Rawat N, Lehrman SG, Aronow WS. Management of massive and nonmassive pulmonary embolism. Archives of Medical Science. 2012; 8 (6): 957. doi : 10.5114/ aoms.2012.32402
  • 10. Tapson VF, editor Thrombolytic therapy for acute pulmonary embolism. Seminars in thrombosis and hemostasis; 2013: Thieme Medical Publishers doi: 10.1055/s-0033-1334145
  • 11. Cavallazzi R, Nair A, Vasu T, Marik PE. Natriuretic peptides in acute pulmonary embolism: a systematic review. Intensive Care Medicine 2008; 34 (12): 2147-2156. doi: 10.1007/s00134-008- 1214-5
  • 12. Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing G-J et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS) The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). European Heart Journal 2020; 41 (4): 543-603. doi: 10.1093/eurheartj/ehz405
  • 13. Liu W, Zhang Y, Lu L, Wang L, Chen M et al. Expression and correlation of hypoxia-inducible factor-1α (HIF-1α) with pulmonary artery remodeling and right ventricular hypertrophy in experimental pulmonary embolism. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research. 2017; 23: 2083. doi: 10.12659/MSM.900354
  • 14. Jin M-L, Zou Z-H, Tao T, Li J, Xu J et al. Effect of the Recombinant Adenovirus-Mediated HIF-1 Alpha on the Expression of VEGF in the Hypoxic Brain Microvascular Endothelial Cells of Rats. Neuropsychiatric Disease and Treatment 2020; 16: 397. doi: 10.2147/NDT.S238616
  • 15. Rutanen J, Rissanen TT, Markkanen JE, Gruchala M, Silvennoinen Pi et al. Adenoviral catheter-mediated intramyocardial gene transfer using the mature form of vascular endothelial growth factor-D induces transmural angiogenesis in porcine heart. Circulation 2004; 109 (8): 1029-1035. doi: 10.1161/01. CIR.0000115519.03688.A2