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Increased arginase levels in heart failure represent a therapeutic target to rescue microvascular perfusion.
MedLine Citation:
PMID:  23075998     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-17
Journal Detail:
Title:  Clinical hemorheology and microcirculation     Volume:  -     ISSN:  1875-8622     ISO Abbreviation:  Clin. Hemorheol. Microcirc.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9709206     Medline TA:  Clin Hemorheol Microcirc     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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