Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Heger, Lukas Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Kerber, Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED Hortmann, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Robinson, Samuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauler, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Stallmann, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Duerschmied, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Bode, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Hehrlein, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Ahrens, Ingo UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language INDUCIBLE FACTOR-I; SYSTEMIC-SCLEROSIS; HEME OXYGENASE-1; OXIDATIVE STRESS; HUMAN MONOCYTES; DIGITAL ULCERS; MESSENGER-RNA; DOUBLE-BLIND; HYPOXIA; BOSENTAN Multiple languages Chemistry, Multidisciplinary; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15256