Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0015441
Title: Metabolomic profiling of cellular responses to carvedilol enantiomers in vascular smooth muscle cells
Authors: Wang M.
Bai J.
Chen W.N.
Ching C.B. 
Keywords: calcium ion
carvedilol
inositol
myristic acid
palmitic acid
pyroglutamic acid
serine
threonine
alanine
beta adrenergic receptor blocking agent
calcium
carbazole derivative
carvedilol
propanolamine derivative
article
calcium cell level
cell line
cell metabolism
controlled study
drug effect
in vitro study
mass fragmentography
metabolite
metabolomics
smooth muscle fiber
vascular smooth muscle
animal
chemistry
cytology
intracellular space
metabolism
metabolome
methodology
principal component analysis
rat
smooth muscle fiber
stereoisomerism
Adrenergic beta-Antagonists
Alanine
Animals
Calcium
Carbazoles
Cell Line
Gas Chromatography-Mass Spectrometry
Intracellular Space
Metabolome
Metabolomics
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
Principal Component Analysis
Propanolamines
Rats
Stereoisomerism
Issue Date: 2010
Citation: Wang M., Bai J., Chen W.N., Ching C.B. (2010). Metabolomic profiling of cellular responses to carvedilol enantiomers in vascular smooth muscle cells. PLoS ONE 5 (11) : e15441. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0015441
Rights: Attribution 4.0 International
Abstract: Carvedilol is a non-selective ?-blocker indicated in the treatment of hypertension and heart failure. Although the differential pharmacological effects of individual Carvedilol enantiomer is supported by preceding studies, the cellular response to each enantiomer is not well understood. Here we report the use of GC-MS metabolomic profiling to study the effects of Carvedilol enantiomers on vascular smooth muscle cells (A7r5) and to shed new light on molecular events underlying Carvedilol treatment. The metabolic analysis revealed alternations in the levels of 8 intracellular metabolites and 5 secreted metabolites in A7r5 cells incubated separately with S- and R-Carvedilol. Principal component analysis of the metabolite data demonstrated the characteristic metabolic signatures in S- and R-Carvedilol-treated cells. A panel of metabolites, including L-serine, L-threonine, 5-oxoproline, myristic acid, palmitic acid and inositol are closely correlated to the vascular smooth muscle contraction. Our findings reveal the differentiating metabolites for A7r5 cells incubated with individual enantiomer of Carvedilol, which opens new perspectives to employ metabolic profiling platform to study chiral drug-cell interactions and aid their incorporation into future improvement of ?-blocker therapy. © 2010 Wang et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161798
ISSN: 19326203
DOI: 10.1371/journal.pone.0015441
Rights: Attribution 4.0 International
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