Universität zu Köln

Nishat, Shamama, Klinke, Anna, Baldus, Stephan, Khan, Luqman Ahmad and Basir, Seemi Farhat (2014). Increased A(3)AR-dependent Vasoconstriction in Diabetic Mice Is Promoted by Myeloperoxidase. J. Cardiovasc. Pharmacol., 64 (5). S. 465 - 473. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1533-4023

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Abstract

Vascular dysfunction importantly contributes to mortality and morbidity in various cardiac and metabolic diseases. Among endogenous molecules regulating vascular tone is adenosine, with the adenosine A(3) receptor (A(3)AR) exerting cardioprotective properties in ischemia and reperfusion. However, overexpression of A(3)AR is suggested to result in vascular dysfunction and inflammation. The leukocyte enzyme myeloperoxidase (MPO) is an important modulator of vascular function with nitric oxide-consuming and proinflammatory properties. Increased MPO plasma levels are observed in patients with cardiovascular disorders like heart failure, acute coronary syndromes, and arrhythmias. Given that vascular dysfunction and inflammation are also hallmarks of diabetes, the role of MPO in adenosine-dependent vasomotor function was investigated in a murine model of diabetes mellitus. Wild-type (WT) and MPO-deficient (Mpo(-/-)) mice were treated with Streptozotocin (STZ), which induced an increase of MPO plasma levels in WT mice and led to enhanced aortic superoxide generation as assessed by dihydroethidium staining in STZ-treated WT mice as compared with controls. The vasoconstriction of aortic segments in response to the A(3)AR agonist Cl-IB-MECA (2-Chloro-N6-(3-iodobenzyl)-N-methyl-5-carbamoyladenosine) as determined by isometric force measurements was augmented in diabetic WT as compared with diabetic Mpo(-/-) mice. Moreover, A(3)AR protein expression was enhanced in STZ-treated mice but was attenuated by MPO deficiency. The current data reveal an MPO-mediated increase of vascular A(3)AR expression under diabetic conditions, which leads to enhanced vasoconstriction in response to A(3)AR agonists and discloses an additional mechanism of MPO-mediated vascular dysfunction.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nishat, Shamama UNSPECIFIED UNSPECIFIED UNSPECIFIED Klinke, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Baldus, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Khan, Luqman Ahmad UNSPECIFIED UNSPECIFIED UNSPECIFIED Basir, Seemi Farhat UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-424257
DOI:	10.1097/FJC.0000000000000139
Journal or Publication Title:	J. Cardiovasc. Pharmacol.
Volume:	64
Number:	5
Page Range:	S. 465 - 473
Date:	2014
Publisher:	LIPPINCOTT WILLIAMS & WILKINS
Place of Publication:	PHILADELPHIA
ISSN:	1533-4023
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language A(3) ADENOSINE RECEPTOR; ACUTE CORONARY SYNDROMES; OXIDATIVE STRESS; ENDOTHELIAL DYSFUNCTION; THERAPEUTIC TARGETS; ARTERY-DISEASE; EXPRESSION; HEART; ATHEROSCLEROSIS; COMPLICATIONS Multiple languages Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42425