PMID- 24276258 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20131126 LR - 20211021 IS - 1424-8247 (Print) IS - 1424-8247 (Electronic) IS - 1424-8247 (Linking) VI - 6 IP - 6 DP - 2013 May 27 TI - Dysregulation of the Mammalian Target of Rapamycin and p27Kip1 Promotes Intimal Hyperplasia in Diabetes Mellitus. PG - 716-27 LID - 10.3390/ph6060716 [doi] AB - The proliferation and migration of vascular smooth muscle cells (VSMCs) in the intima of an artery, known as intimal hyperplasia, is an important component of cardiovascular diseases. This is seen most clearly in the case of in-stent restenosis, where drug eluting stents are used to deliver agents that prevent VSMC proliferation and migration. One class of agents that are highly effective in the prevention of in-stent restenosis is the mammalian Target of Rapamycin (mTOR) inhibitors. Inhibition of mTOR blocks protein synthesis, cell cycle progression, and cell migration. Key to the effects on cell cycle progression and cell migration is the inhibition of mTOR-mediated degradation of p27Kip1 protein. p27Kip1 is a cyclin dependent kinase inhibitor that is elevated in quiescent VSMCs and inhibits the G1 to S phase transition and cell migration. Under normal conditions, vascular injury promotes degradation of p27Kip1 protein in an mTOR dependent manner. Recent reports from our lab suggest that in the presence of diabetes mellitus, elevation of extracellular signal response kinase activity may promote decreased p27Kip1 mRNA and produce a relative resistance to mTOR inhibition. Here we review these findings and their relevance to designing treatments for cardiovascular disease in the presence of diabetes mellitus. FAU - Woods, Thomas Cooper AU - Woods TC AD - Tulane Heart and Vascular Institute and the Department of Physiology, School of Medicine, Tulane University, 1430 Tulane Avenue, SL-48, New Orleans, LA 70112, USA. twoods3@tulane.edu. LA - eng GR - P20 GM103514/GM/NIGMS NIH HHS/United States GR - P20 RR018766/RR/NCRR NIH HHS/United States PT - Journal Article DEP - 20130527 PL - Switzerland TA - Pharmaceuticals (Basel) JT - Pharmaceuticals (Basel, Switzerland) JID - 101238453 PMC - PMC3816729 EDAT- 2013/11/28 06:00 MHDA- 2013/11/28 06:01 PMCR- 2013/06/01 CRDT- 2013/11/27 06:00 PHST- 2013/01/14 00:00 [received] PHST- 2013/05/01 00:00 [revised] PHST- 2013/05/08 00:00 [accepted] PHST- 2013/11/27 06:00 [entrez] PHST- 2013/11/28 06:00 [pubmed] PHST- 2013/11/28 06:01 [medline] PHST- 2013/06/01 00:00 [pmc-release] AID - ph6060716 [pii] AID - pharmaceuticals-06-00716 [pii] AID - 10.3390/ph6060716 [doi] PST - epublish SO - Pharmaceuticals (Basel). 2013 May 27;6(6):716-27. doi: 10.3390/ph6060716.