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Updated: Aug 25, 2026

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
10:21

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Rapamycin effects transcriptional programs in smooth muscle cells controlling proliferative and inflammatory

Dietlind Zohlnhöfer1, Thomas G Nührenberg, Franz-Josef Neumann

  • 1Deutsches Herzzentrum, München, Germany. zohlnhoefer@dhm.mhn.de

Molecular Pharmacology
|March 27, 2004
PubMed

Insights

Rapamycin inhibits neointima formation by reducing coronary artery smooth muscle cell (CASMC) proliferation and monocyte adhesion. It affects gene expression, including down-regulating E2F-1 and endothelial monocyte-activating polypeptide-II (EMAP-II).

Area of Science:

  • Cardiovascular Biology
  • Molecular Pharmacology
  • Cellular Signaling

Background:

  • Neointima formation, driven by coronary artery smooth muscle cell (CASMC) proliferation and monocyte infiltration, causes restenosis after stenting.
  • Rapamycin is clinically used to inhibit neointima formation, acting via mammalian target of rapamycin (mTOR) kinase.

Purpose of the Study:

  • To investigate mTOR expression in human neointima.
  • To elucidate the effects of rapamycin on global gene expression in CASMCs.

Main Methods:

  • Comparative gene expression analysis of CASMCs treated with rapamycin.
  • Assessment of mTOR phosphorylation and nuclear translocation in neointimal CASMCs.

Main Results:

  • Increased mTOR phosphorylation and nuclear translocation observed in neointimal CASMCs.
  • Rapamycin down-regulated E2F-1 and related genes, impacting cell cycle progression.
  • Rapamycin decreased endothelial monocyte-activating polypeptide-II (EMAP-II) expression, reducing CASMC adhesiveness for monocytes.

Conclusions:

  • Rapamycin reduces CASMC proliferation by down-regulating cell cycle-related genes.
  • Rapamycin may mitigate inflammatory responses by decreasing EMAP-II, thereby reducing CASMC-monocyte adhesion.

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