PMID- 19129735 OWN - NLM STAT- MEDLINE DCOM- 20100920 LR - 20211020 IS - 1533-4023 (Electronic) IS - 0160-2446 (Print) IS - 0160-2446 (Linking) VI - 53 IP - 1 DP - 2009 Jan TI - Sera from patients with diabetes do not alter the effect of mammalian target of rapamycin inhibition on smooth muscle cell proliferation. PG - 86-9 LID - 10.1097/FJC.0b013e318195b588 [doi] AB - 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. FAU - Moss, Stephanie C AU - Moss SC AD - Ochsner Clinic Foundation, New Orleans, LA 70121, USA. FAU - Lightell, Daniel Jr AU - Lightell D Jr FAU - Deichmann, Richard E Jr AU - Deichmann RE Jr FAU - Woods, T Cooper AU - Woods TC LA - eng GR - P20 RR018766/RR/NCRR NIH HHS/United States GR - P20 RR018766-066844/RR/NCRR NIH HHS/United States GR - P20RR018766-06/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cardiovasc Pharmacol JT - Journal of cardiovascular pharmacology JID - 7902492 RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Aged MH - Animals MH - Cell Proliferation/*drug effects MH - Diabetes Mellitus/metabolism MH - Diabetes Mellitus, Type 2/metabolism MH - Drug-Eluting Stents MH - Female MH - Humans MH - Male MH - Mammals/metabolism MH - Middle Aged MH - Muscle, Smooth/metabolism MH - Myocytes, Smooth Muscle/*drug effects/metabolism MH - Sirolimus/metabolism/*pharmacology PMC - PMC2891793 MID - NIHMS117983 EDAT- 2009/01/09 09:00 MHDA- 2010/09/21 06:00 PMCR- 2010/06/25 CRDT- 2009/01/09 09:00 PHST- 2009/01/09 09:00 [entrez] PHST- 2009/01/09 09:00 [pubmed] PHST- 2010/09/21 06:00 [medline] PHST- 2010/06/25 00:00 [pmc-release] AID - 10.1097/FJC.0b013e318195b588 [doi] PST - ppublish SO - J Cardiovasc Pharmacol. 2009 Jan;53(1):86-9. doi: 10.1097/FJC.0b013e318195b588.