Rapamycin Inhibits Release of Tumor Necrosis Factor-α from Human Vascular Smooth Muscle Cells

Adkins, Jonathan R.; Castresana, Manuel R.; Zhongbiao Wang; Newman, Walter H.
May 2004
American Surgeon;May2004, Vol. 70 Issue 5, p384
Academic Journal
Neointimal proliferation with plaque formation is the principal cause of coronary artery disease. In the neointima, inflammatory cytokines like tumor necrosis factor-α (TNF-α) are expressed by vascular smooth muscle cells (VSMCs). These cytokines stimulate proliferation and migration of VSMCs, events that are crucial to neointima formation. Stems, liberating rapamycin, have been shown to reduce neointima formation in human coronary arteries. The purpose of this study was to determine if rapamycin could inhibit the production of TNF-α by VSMCs. With institutional review board approval, VSMCs were cultured from saphenous vein segments obtained from five patients. Cells were identified as VSMC by immunostaining for smooth muscle α-actin. Cells were exposed to bacterial lipopolysaccharide (LPS), LPS plus rapamycin, or LPS plus isoproterenol for 24 hours. Cells with no treatment served as controls. The culture medium was then removed and analyzed for TNF-α. Additionally, the effect of treatment on viability was determined by assay of mitochondria) activity. TNF-α released into the culture medium is expressed as pg TNF-α/mg cell protein. Statistical analysis was by ANOVA. In control cells, TNF-α was undetectable in the culture medium. The addition of LPS (10 µg/mL) increased TNF-α release to 4312 ± 705 pg/mg at 24 hours. The addition of 1 ng/mL rapamycin with LPS reduced TNF-α production 50 per cent (P < 0.01 vs LPS alone). A similar reduction of TNF-α release was seen with 1 µM isoproterenol. LPS, rapamycin, or isoproterenol did not affect cell viability. These data show that rapamycin effectively inhibits the release of TNF-α from VSMCs stimulated with inflammatory mediators like LPS. Rapamycin is as effective as agents that raise intracellular cyclic AMP (e.g., isoproterenol). Therefore, a potential mechanism for the...


Related Articles

  • Economic evaluation of sirolimus-eluting stents. Shrive, Fiona M.; Manns, Braden J.; Galbraith, P. Diane; Knudtson, Merril L.; Ghali, William A. // CMAJ: Canadian Medical Association Journal;2/1/2005, Vol. 172 Issue 3, p345 

    Background: Sirolimus-eluting stents have recently been shown to reduce the risk of restenosis among patients who undergo percutaneous coronary intervention (PCI). Given that sirolimus-eluting stents cost about 4 times as much as conventional stents, and considering the volume of PCI procedures,...

  • OF SPECIAL INTEREST.  // American Journal of Health-System Pharmacy;11/1/2005, Vol. 62 Issue 21, p2193 

    Discusses the significance of paclitaxel-eluting stents in coronary artery disease. Inhibition of the injury-related proliferation of vascular smooth muscle cells; Cell cycle and mechanism of action of paclitaxel, a cytotoxic drug; Implication of enteric-coated mycophenolate sodium for...

  • Rapamycin inhibits human in stent restenosis vascular smooth muscle cells independently of pRB phosphorylation and p53. Rosner, Dalya; McCarthy, Nicola; Bennett, Martin // Cardiovascular Research;Jun2005, Vol. 66 Issue 3, p601 

    Abstract: Objective: Drug-eluting stents containing the immunosuppressant rapamycin markedly inhibit in stent restenosis (ISR). However, the molecular mechanisms that underlie its effect on ISR-derived vascular smooth muscle cells (VSMCs), as opposed to normal VSMCs, are unknown. Specifically,...

  • Stent Implantation Activates RhoA in Human Arteries: Inhibitory Effect of Rapamycin. Guérin, Patrice; Sauzeau, Vincent; Rolli-Derkinderen, Malvyne; Al Habbash, Oussama; Scalbert, Elizabeth; Crochet, Dominique; Pacaud, Pierre; Loirand, Gervaise // Journal of Vascular Research;2005, Vol. 42 Issue 1, p21 

    In-stent restenosis is a novel pathobiologic process resulting from vascular smooth muscle cell (VSMC) proliferation, migration and excessive matrix production. The present study was designed to assess the activity of RhoA, a major regulator of VSMC proliferation and migration, after stenting...

  • Regulation of catalytic activity of S6 kinase 2 during cell cycle. Derek Boyer; Rene Quintanilla; Kay Lee-Fruman // Molecular & Cellular Biochemistry;Jan2008, Vol. 307 Issue 1/2, p59 

    Abstract  Ribosomal S6 kinase 2 (S6K2) is one of the kinases regulated by the mammalian target of rapamycin (mTOR) signaling pathway. Although it has been identified as a kinase homologous to S6K1, evidence suggests that the two kinases have non-overlapping functions, and the biological...

  • Pseudohyphal differentiation defect due to mutations in GPCR and ammonium signaling is suppressed by low glucose concentration: a possible integrated role for carbon and nitrogen limitation. Iyer, Revathi S.; Das, Maitreyi; Jayadeva Bhat, Paike // Current Genetics;Aug2008, Vol. 54 Issue 2, p71 

    In response to carbon and/or nitrogen limitation, diploid cells of Saccharomyces cerevisiae either sporulate or develop pseudohyphae. Although the signal transduction pathways leading to these developmental changes have been extensively studied, how nutritional signals are integrated is not...

  • Emodin inhibits coxsackievirus B3 replication via multiple signalling cascades leading to suppression of translation. Huifang M. Zhang; Ye Qiu; Xin Ye; Hanson, Paul; Hongxing Shen; Decheng Yang; Fengping Wang // Biochemical Journal;2/15/2016, Vol. 473 Issue 4, p373 

    CVB3 (coxsackievirus 3) is a primary causal agent of viral myocarditis. Emodin is a natural compound isolated from certain plant roots. In the present study, we found that emodin inhibited CVB3 replication in vitro and in mice, and now we report an unrecognized mechanism by which emodin inhibits...

  • Sirolimus Eluting Stents. Hu, Patrick P.; Mahmud, Ehtisham // Clinical Medicine Insights: Therapeutics;2010, Issue 2, p549 

    The sirolimus-eluting stent (SES) Cypher was the first commercially available drug-eluting stent. The use of this stent has resulted in significantly lower rates of restenosis and lesion revascularization compared to bare metal stents and balloon angioplasty. In this review, angiographic and...

  • In-vitro Release of Rapamycin from a Thermosensitive Polymer for the Inhibition of Vascular Smooth Muscle Cell Proliferation. Weiwei Zhu; Masaki, Takahisa; Cheung, Alfred K.; Kern, Steven E. // Journal of Bioequivalence & Bioavailability;May-Jun2009, Vol. 1 Issue 1, p3 

    Hemodialysis arteriovenous grafts are often plagued by stenosis at the anastomosis, which is due to the proliferation of vascular smooth muscle cells (SMCs). To prevent the stenosis, we have been developing a strategy for the sustained perivascular delivery of an antiproliferative agent,...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics