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Open Access Research article

Expression of Hypoxia-Inducible Factor (HIF)-1a-Vascular Endothelial Growth Factor (VEGF)-Inhibitory Growth Factor (ING)-4- axis in sarcoidosis patients

Argyris Tzouvelekis1*, Paschalis Ntolios2, Andreas Karameris3, Anastasios Koutsopoulos4, Panagiotis Boglou1, Andreas Koulelidis1, Kostas Archontogeorgis1, George Zacharis1, Fotis Drakopanagiotakis5, Paschalis Steiropoulos1, Stavros Anevlavis1, Vlassis Polychronopoulos5, Dimitrios Mikroulis6 and Demosthenes Bouros1

Author Affiliations

1 Department of Pneumonology, University Hospital of Alexandroupolis, Medical school, Democritus University of Thrace, Thrace, Greece

2 Pulmonary Biochemistry, Centre for Respiratory Research, University College London, London, UK

3 Department of Pathology, Veterans Administration Hospital (N.I.M.T.S), Athens, Greece

4 Department of Pathology, University Hospital of Alexandroupolis, Medical school, Democritus University of Thrace, Thrace, Greece

5 Department of Pneumonology, Sismanogleio General Hospital, Athens, Greece

6 Department of Cardiothoracic Surgery, University Hospital of Alexandroupolis, Medical School, Democritus University of Thrace, Thrace, Greece

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BMC Research Notes 2012, 5:654  doi:10.1186/1756-0500-5-654

Published: 26 November 2012



Sarcoidosis is a granulomatous disorder of unknown etiology. The term of immunoangiostasis has been addressed by various studies as potentially involved in the disease pathogenesis. The aim of the study was to investigate the expression of the master regulator of angiogenesis hypoxia inducible factor (HIF)-1a – vascular endothelial growth factor (VEGF)- inhibitor of growth factor 4-(ING4) - axis within sarcoid granuloma.


A total of 37 patients with sarcoidosis stages II-III were recruited in our study. Tissue microarray technology coupled with immunohistochemistry analysis were applied to video-assisted thoracoscopic surgery (VATS) lung biopsy samples collected from 37 sarcoidosis patients and 24 controls underwent surgery for benign lesions of the lung. Computerized image analysis was used to quantify immunohistochemistry results. qRT-PCR was used to assess HIF-1a and ING4 expression in 10 sarcoidosis mediastinal lymph node and 10 control lung samples.


HIF-1a and VEGF-ING4 expression, both in protein and mRNA level, was found to be downregulated and upregulated, respectively, in sarcoidosis samples compared to controls. Immunohistochemistry coupled with computerized image analysis revealed minimal expression of HIF-1a within sarcoid granulomas whereas an abundant staining of ING4 and VEGF in epithelioid cells was also visualized.


Our data suggest an impairment of the HIF-1a – VEGF axis, potentialy arising by ING4 overexpression and ultimately resulting in angiostasis and monocyte recruitment within granulomas. The concept of immunoangiostasis as a possible protection mechanism against antigens of infectious origin needs further research to be verified.