Heger, Lukas Andreas, Kerber, Mark, Hortmann, Marcus, Robinson, Samuel, Mauler, Maximilian, Stallmann, Daniela, Duerschmied, Daniel, Bode, Christoph, Hehrlein, Christoph and Ahrens, Ingo (2019). Expression of the oxygen-sensitive transcription factor subunit HIF-1 alpha in patients suffering from secondary Raynaud syndrome. Acta Pharmacol. Sin., 40 (4). S. 500 - 507. SHANGHAI: ACTA PHARMACOLOGICA SINICA. ISSN 1745-7254

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Abstract

Anti-ischemic therapy remains a challenge due to the complexity of hypoxia response pathways. Hypoxia-inducible factor (HIF)-1 is a heterodimer transcription factor consisting of 2 subunits, HIF-1 alpha and HIF-1 beta. Hypoxia-dependent activation of HIF-1 alpha regulates cellular O-2 homeostasis. Raynaud syndrome (RS), as a comorbidity of the autoimmune disease systemic sclerosis (SS), is characterized by vasospasms that limit blood flow to the limbs, resulting in hypoxia. A single-center randomized study was conducted to compare prostaglandin E1 (PgE1) therapy with a treatment combining PgE1 and an endothelin-1 blocker, bosentan. A total of 30 patients suffering from SS with RS were enrolled. We examined the regulation of HIF-1 alpha, its target heme oxygenase-1 (HMOX-1), and the serum levels of the HIF-1 alpha protein in a subset of patients as well as in ten healthy individuals. The expression of HIF-1 alpha and HMOX-1 in monocytes was measured using absolute plasmid-based quantitative real-time PCR, whereas serum HIF-1 alpha levels were measured with ELISA. Samples were taken at the time of randomization and after 24 weeks. We found that HIF-1 alpha and HMOX-1 mRNA expression in monocytes and serum HIF-1 alpha protein levels were significantly higher in the SS/RS patients compared to the healthy control group. Single-drug therapy significantly increased HIF-1 alpha and HMOX-1 mRNA expression in monocytes and serum HIF-1 alpha protein levels in the SS/RS patients compared to those at the time of randomization, whereas combining PgE1 with an endothelin-1 blocker prevented the further increases in HIF-1 alpha and HMOX-1 expression. We propose HIF-1 alpha and HMOX-1 as novel markers for anti-ischemic therapy in RS.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Heger, Lukas AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kerber, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hortmann, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robinson, SamuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mauler, MaximilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stallmann, DanielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duerschmied, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bode, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hehrlein, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ahrens, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-152562
DOI: 10.1038/s41401-018-0055-1
Journal or Publication Title: Acta Pharmacol. Sin.
Volume: 40
Number: 4
Page Range: S. 500 - 507
Date: 2019
Publisher: ACTA PHARMACOLOGICA SINICA
Place of Publication: SHANGHAI
ISSN: 1745-7254
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INDUCIBLE FACTOR-I; SYSTEMIC-SCLEROSIS; HEME OXYGENASE-1; OXIDATIVE STRESS; HUMAN MONOCYTES; DIGITAL ULCERS; MESSENGER-RNA; DOUBLE-BLIND; HYPOXIA; BOSENTANMultiple languages
Chemistry, Multidisciplinary; Pharmacology & PharmacyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15256

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