Next Article in Journal
Database-Guided Discovery of Potent Peptides to Combat HIV-1 or Superbugs
Previous Article in Journal
Virtual Lead Identification of Farnesyltransferase Inhibitors Based on Ligand and Structure-Based Pharmacophore Techniques
Previous Article in Special Issue
Protein Kinase C Inhibitors as Modulators of Vascular Function and Their Application in Vascular Disease
Article Menu

Export Article

Open AccessReview
Pharmaceuticals 2013, 6(6), 716-727; doi:10.3390/ph6060716

Dysregulation of the Mammalian Target of Rapamycin and p27Kip1 Promotes Intimal Hyperplasia in Diabetes Mellitus

1
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
2
Department of Pharmacology & Experimental Therapeutics, LSU Health Sciences Center—New Orleans, New Orleans, LA 70112, USA 
Received: 14 January 2013 / Revised: 1 May 2013 / Accepted: 8 May 2013 / Published: 27 May 2013
(This article belongs to the Special Issue Protein Kinase Inhibitors)
View Full-Text   |   Download PDF [182 KB, uploaded 27 May 2013]   |  

Abstract

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. View Full-Text
Keywords: intimal hyperplasia; p27Kip1; mammalian Target of Rapamycin; diabetes mellitus; vascular smooth muscle cells intimal hyperplasia; p27Kip1; mammalian Target of Rapamycin; diabetes mellitus; vascular smooth muscle cells
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Woods, T.C. Dysregulation of the Mammalian Target of Rapamycin and p27Kip1 Promotes Intimal Hyperplasia in Diabetes Mellitus. Pharmaceuticals 2013, 6, 716-727.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Pharmaceuticals EISSN 1424-8247 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top