Metabolomic profiling of cellular responses to carvedilol enantiomers in vascular smooth muscle cells.
Carvedilol is a non-selective β-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 β-blocker therapy.
School of Chemical and Biomedical Engineering, College of Engineering, Nanyang Technological University, Singapore, Singapore.
Mingxuan
M
Wang
Jing
J
Bai
Wei Ning
WN
Chen
Chi Bun
CB
Ching
D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000494:pharmacology; D000409:Alanine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology*; D000077261:Carvedilol; D002460:Cell Line; D008401:Gas Chromatography-Mass Spectrometry; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D025341:Principal Component Analysis; D011412:Propanolamines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D000409:Alanine; D002118:Calcium