Glutamine supplementation alleviates vasculopathy and corrects metabolic profile in an in vivo model of endothelial cell dysfunction.

Citation data:

PloS one, ISSN: 1932-6203, Vol: 8, Issue: 6, Page: e65458

Publication Year:
2013
Usage 3195
Full Text Views 3094
Abstract Views 64
Views 25
Downloads 12
Captures 18
Readers 15
Exports-Saves 3
Social Media 1
Shares, Likes & Comments 1
Citations 8
Citation Indexes 8
PMID:
23776484
DOI:
10.1371/journal.pone.0065458, 10.1371/journal.pone.0065458.g008, 10.1371/journal.pone.0065458.g001, 10.1371/journal.pone.0065458.g003, 10.1371/journal.pone.0065458.g002, 10.1371/journal.pone.0065458.g005, 10.1371/journal.pone.0065458.g004, 10.1371/journal.pone.0065458.g007, 10.1371/journal.pone.0065458.g006
PMCID:
PMC3679132, 3679132
Author(s):
Francesco Addabbo, Qiuying Chen, Dhara P. Patel, May Rabadi, Brian Ratliff, Frank Zhang, Jean-Francois Jasmin, Michael Wolin, Michael Lisanti, Steven S. Gross, Michael S. Goligorsky, Tobias Eckle Show More Hide
Publisher(s):
Public Library of Science (PLoS), Figshare
Tags:
Biochemistry, Genetics and Molecular Biology, Agricultural and Biological Sciences, Medicine, Biological Sciences, anatomy and physiology, cardiovascular system, circulatory physiology, biochemistry, metabolism, carbohydrate metabolism, metabolic pathways, model organisms, animal models, mouse, systems biology, cardiovascular, vascular biology, supplementation, dose-dependently, improves, acetylcholine-induced, vasodilatatory, thoracic, aortic, rings, caveolin-1, transgenic, knock-out, suppresses, vasorelaxation, glutamine, endothelium-dependent, l-nmma-treated, kidney, metabolite, offset, plasma, mice, l-nmma, treated, 30, summarizing, metabolomic, findings, pathways, l-glutamine, supplementation-induced, amelioration, vascolopathy, lysophospholipid, alleviates, vasculopathy, corrects, metabolic, vivo, endothelial
article media
article description
Endothelial Cell Dysfunction (ECD) is a recognized harbinger of a host of chronic cardiovascular diseases. Using a mouse model of ECD triggered by treatment with L-Nω-methylarginine (L-NMMA), we previously demonstrated that renal microvasculature displays a perturbed protein profile, including diminished expression of two key enzymes of the Krebs cycle associated with a Warburg-type suppression of mitochondrial metabolism. We hypothesized that supplementation with L-glutamine (GLN), that can enter the Krebs cycle downstream this enzymatic bottleneck, would normalize vascular function and alleviate mitochondrial dysfunction. To test this hypothesis, mice with chronic L-NMMA-induced ECD were co-treated with GLN at different concentrations for 2 months. Results confirmed that L-NMMA led to a defect in acetylcholine-induced relaxation of aortic rings that was dose-dependently prevented by GLN. In caveolin-1 transgenic mice characterized by eNOS inactivation, L-NMMA further impaired vasorelaxation which was partially rescued by GLN co-treatment. Pro-inflammatory profile induced by L-NMMA was blunted in mice co-treated with GLN. Using an LC/MS platform for metabolite profiling, we sought to identify metabolic perturbations associated with ECD and offset by GLN supplementation. 3453 plasma molecules could be detected with 100% frequency in mice from at least one treatment group. Among these, 37 were found to be differentially expressed in a 4-way comparison of control vs. LNMMA both with and without GLN. One of such molecules, hippuric acid, an "uremic toxin" was found to be elevated in our non-uremic mice receiving L-NMMA, but normalized by treatment with GLN. Ex vivo analysis of hippuric acid effects on vasomotion demonstrated that it significantly reduced acetylcholine-induced vasorelaxation of vascular rings. In conclusion, functional and metabolic profiling of animals with early ECD revealed macrovasculopathy and that supplementation GLN is capable of improving vascular function. Metabolomic analyses reveal elevation of hippuric acid, which may further exacerbate vasculopathy even before the development of uremia.

This article has 0 Wikipedia mention.