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

Buğra Kerget,Ömer Araz,Seda Aşkin,Dursun Erol Afşi̇n,Alperen Aksakal

doi:10.3906/sag-1908-93

Abstract

Background/aimPulmonary 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-1α) and clinical course and prognosis in patients with intermediate low-risk, intermediate high-risk, and high-risk PE.Materials and methodsThe 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-1α levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kit.ResultsComparison of HIF-1α levels revealed a statistically significant difference between the groups in proportion to clinical scoring (P = 0.001 for all). Comparison of initial HIF-1α and troponin levels in intermediate high-risk PE patients given thrombolytic therapy and those treated with enoxaparin sodium showed that HIF-1α 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).ConclusionHIF-1α 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.

Highlights

Pulmonary embolism (PE) is usually an early complication of deep venous thrombosis (DVT) and can cause high morbidity and mortality rates if not diagnosed and treated early [1]
Comparison of initial hypoxia inducible factor-1α (HIF-1α) and troponin levels in intermediate high-risk PE patients given thrombolytic therapy and those treated with enoxaparin sodium showed that HIF-1α 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)
HIF-1α can be used in the PE clinical risk stratification and monitoring of PE and may serve as a valuable early indicator in intermediate high-risk PE, for which early reperfusion therapy is important

Summary

Introduction

Pulmonary embolism (PE) is usually an early complication of deep venous thrombosis (DVT) and can cause high morbidity and mortality rates if not diagnosed and treated early [1]. Microinfarcts resulting in malperfusion in the right ventricle cause troponin-I release from the myocardium as an indicator of cell damage, while increased levels of HIF1α and especially VEGF improve the existing pathology [3]. Right ventricle dilation stimulates the myocardial tissue and vascular bed to synthesize various cytokines, especially hypoxia inducible factor-1α (HIF-1α), to regulate oxygenation and promote neovascularization. HIF-1α induces vascular endothelial growth factor (VEGF) synthesis to initiate vascularization, while glutathione peroxidase activity is increased to prevent reperfusion injury [4]. In studies using rat models of experimental PE, it was determined that HIF-1α was expressed at a higher level than in the control group and that this synthesis primarily occurred in the myocardial tissue and vascular bed [3,7]

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