In human endothelial cells rapamycin causes mTORC2 inhibition and impairs cell viability and function

• Published in: Cardiovascular research Vol. 78; no. 3; pp. 563 - 571
• Main Authors: Barilli, Amelia, Visigalli, Rossana, Sala, Roberto, Gazzola, Gian C., Parolari, Alessandro, Tremoli, Elena, Bonomini, Sabrina, Simon, Alexandra, Closs, Ellen I., Dall’Asta, Valeria, Bussolati, Ovidio
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.06.2008
• Subjects: Adaptor Proteins, Signal Transducing; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Blotting, Western; Cardiology. Vascular system; Cardiovascular Agents - toxicity; Carrier Proteins - metabolism; Caspase 3 - metabolism; Cell Movement - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; E-Selectin - metabolism; Endothelial Cells - drug effects; Endothelial Cells - enzymology; Endothelial Cells - metabolism; Endothelial Cells - pathology; Enzyme-Linked Immunosorbent Assay; Humans; Immunoprecipitation; L-Lactate Dehydrogenase - metabolism; Mechanistic Target of Rapamycin Complex 1; Medical sciences; Microscopy, Confocal; mTOR; Multiprotein Complexes; Necrosis; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - metabolism; Pharmacology. Drug treatments; Polymerase Chain Reaction; Protein Kinases - metabolism; Proteins - metabolism; Rapamycin-Insensitive Companion of mTOR Protein; Regulatory-Associated Protein of mTOR; Restenosis; Ribosomal Protein S6 Kinases, 70-kDa - metabolism; Sirolimus - toxicity; Stress Fibers - drug effects; Stress Fibers - metabolism; Tacrolimus - pharmacology; Theophylline - analogs & derivatives; Time Factors; TNFalpha; TOR Serine-Threonine Kinases; Transcription Factors - antagonists & inhibitors; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation; Restenosis; mTOR; Nitric oxide; TNFalpha; Apoptosis; Human; Endothelial cell; Cell function; TNF alpha; Sirolimus; Phlebology; Antibiotic; Tumor necrosis factor; Circulatory system; Inhibition; Antibacterial agent; Cardiology; Viability

Aim Drug-eluting stents are widely used to prevent restenosis but are associated with late endothelial damage. To understand the basis for this effect, we have studied the consequences of a prolonged incubation with rapamycin on the viability and functions of endothelial cells. Methods and results H...