| Increased arginase levels in heart failure represent a therapeutic target to rescue microvascular perfusion. | |
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MedLine Citation:
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PMID: 23075998 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Objectives: Heart failure (HF) is defined as the incapability of the heart to serve the tissues adequately with blood. This includes changes in microvascular perfusion. A mechanism aggravating perfusion disturbances in HF is endothelial dysfunction by reduced bioavailability of nitric oxide (NO). A mechanism possibly contributing to low NO bioavailability is the upregulation of arginase. Therefore, we investigated circulating arginase levels in patients with HF and its consequences for microvascular perfusion. Methods: A first group consisted of eighty patients with chronic HF. Patients were characterized by echocardiography and laboratory values. Arginase 1 levels were determined using a commercially available ELISA. A second experimental group included eight patients with severe heart failure. Using sidestream darkfield intravital microscopy sublingual microcirculation was quantified before and after the topical incubation of nor-NOHA as arginase inhibitor and L-NMMA as NO synthase inhibitor. Results: Circulating arginase-1 levels were significantly higher in patients with heart failure compared to controls (p < 0.001). Patients with severe heart failure (NYHA III/IV) had significantly higher arginase-1 levels compared to patients with mild heart failure (p < 0.01, NYHA I/II). Sublingual perfused capillary density increased significantly (p < 0.01) following incubation with nor-NOHA. However, this effect was abolished when nor-NOHA was co-incubated with L-NMMA. Conclusions: In conclusion, circulating arginase 1 levels are elevated in patients with HF. A topical inhibition of arginase in these patients leads to improved microcirculation by a NO dependent mechanism. Inhibition of arginase is a possible therapeutic target to rescue microcirculation in patients with HF. |
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Authors:
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-17 |
Journal Detail:
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Title: Clinical hemorheology and microcirculation Volume: - ISSN: 1875-8622 ISO Abbreviation: Clin. Hemorheol. Microcirc. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9709206 Medline TA: Clin Hemorheol Microcirc Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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