Document Detail


Sera from patients with diabetes do not alter the effect of mammalian target of rapamycin inhibition on smooth muscle cell proliferation.
MedLine Citation:
PMID:  19129735     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Clinical studies of drug-eluting stents delivering the mammalian target of rapamycin (mTOR) inhibitor, rapamycin (Sirolimus), have demonstrated a reduced efficacy for these devices in patients with diabetes, which suggests that the mTOR pathway may cease to be dominant in mediating the vascular response to injury under diabetic conditions. We hypothesized that changes in serum composition accompanying diabetes may reduce the role of mTOR in mediating the vascular response to injury. We measured the ability of a median dose of rapamycin (10 nM) to inhibit the proliferation of human coronary artery smooth muscle cells (huCASMCs) stimulated with serum obtained from donors with diabetes (n = 14) and without diabetes (n = 16). In an additional analysis, we compared the effects of rapamycin on huCASMCs stimulated with the serum of donors with metabolic syndrome (n = 15) versus those without (n = 7). There was no difference in the effect of rapamycin on huCASMC proliferation after stimulation with serum from either donors with diabetes or donors with metabolic syndrome compared with the respective controls. We conclude that the changes in the serum composition common to diabetes and metabolic syndrome are insufficient to diminish the role of mTOR in the progression of cardiovascular disease.
Authors:
Stephanie C Moss; Daniel Lightell; Richard E Deichmann; T Cooper Woods
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  53     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2010-06-21     Completed Date:  2010-09-20     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  86-9     Citation Subset:  IM    
Affiliation:
Ochsner Clinic Foundation, New Orleans, LA 70121, USA.
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MeSH Terms
Descriptor/Qualifier:
Aged
Animals
Cell Proliferation / drug effects*
Diabetes Mellitus / metabolism
Diabetes Mellitus, Type 2 / metabolism
Drug-Eluting Stents
Female
Humans
Male
Mammals / metabolism
Middle Aged
Muscle, Smooth / metabolism
Myocytes, Smooth Muscle / drug effects*,  metabolism
Sirolimus / metabolism,  pharmacology*
Grant Support
ID/Acronym/Agency:
P20 RR018766-066844/RR/NCRR NIH HHS; P20RR018766-06/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
53123-88-9/Sirolimus
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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