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Advances in mammalian target of rapamycin kinase inhibitors: application to devices used in the treatment of coronary artery disease.

Authors
  • Jinnouchi, Hiroyuki1
  • Guo, Liang1
  • Sakamoto, Atsushi1
  • Sato, Yu1
  • Cornelissen, Anne1
  • Kawakami, Rika1
  • Mori, Masayuki1
  • Torii, Sho1
  • Kuntz, Salome1
  • Harari, Emanuel1
  • Mori, Hiroyoshi1
  • Fuller, Daniela1
  • Gadhoke, Neel1
  • Fernandez, Raquel1
  • Paek, Ka Hyun1
  • Surve, Dipti1
  • Romero, Maria1
  • Kolodgie, Frank D1
  • Virmani, Renu1
  • Finn, Aloke V1
  • 1 Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA.
Type
Published Article
Journal
Future Medicinal Chemistry
Publisher
"Future Science, LTD"
Publication Date
Jun 01, 2020
Volume
12
Issue
12
Pages
1181–1195
Identifiers
DOI: 10.4155/fmc-2019-0304
PMID: 32431177
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Mammalian target of rapamycin (mTOR) inhibitors have been applied to vascular coronary devices to avoid neointimal growth and have become the predominant pharmacological agents used to prevent restenosis. mTOR inhibitors can affect not only proliferating vascular smooth muscle cells but also endothelial cells and therefore can result in delayed healing of the vessel including endothelialization. Emerging evidence suggests accelerated atherosclerosis due to the downstream negative effects on endothelial barrier functional recovery. The development of neoatherosclerosis within the neointima of drug-eluting stents can result in late thrombotic events. This type of problematic healing response may open the way for specific mTOR kinase inhibitors, such as ATP-competitive mTOR inhibitors. These inhibitors demonstrate a better healing profile than traditional limus-based drug-eluting stent and their clinical efficacy remains unknown.

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