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Rapamycin impairs endothelial cell function in human internal thoracic arteries
David C Reineke1, Else Müller-Schweinitzer2,3, Bernhard Winkler1,3
1Department of Cardiovascular Surgery, University Hospital Berne, Bern, CH-3010, Switzerland.
European Journal of Medical Research
|June 25, 2015
Summary
Rapamycin treatment impairs endothelial function in human coronary arteries by reducing relaxation and down-regulating Akt-phosphorylation via the mTOR signaling axis, without causing endothelial cell injury.
Area of Science:
- Cardiovascular Biology
- Endothelial Function
- Pharmacology
Background:
- Drug-eluting stents are widely used, but their effect on coronary endothelium is not fully understood.
- Evidence suggests rapamycin-eluting stents may impair endothelial function in human coronary arteries.
- Human internal thoracic arteries (ITA) serve as a model to study these effects.
Purpose of the Study:
- To investigate the impact of rapamycin on the functional, morphological, and biochemical properties of the coronary endothelium.
- To elucidate the underlying molecular mechanisms of rapamycin-induced endothelial dysfunction.
Main Methods:
- Organ bath technique to assess functional activity of ITA rings after rapamycin exposure.
- Scanning electron microscopy for morphological evaluation of the endothelial layer.
- Western blotting to measure endothelial nitric oxide synthase (eNOS), mammalian target of rapamycin (mTOR), and protein kinase B (Akt) activation.
Main Results:
- Rapamycin significantly reduced acetylcholine-induced relaxation in ITA rings in a concentration-dependent manner.
- No morphological differences in the endothelial layer were observed via electron microscopy.
- Rapamycin decreased phosphorylation of eNOS, mTOR, and Akt, indicating reduced activation of these key signaling proteins.
Conclusions:
- Rapamycin exposure reduces endothelium-mediated relaxation in ITA.
- This impairment is mediated by down-regulation of Akt-phosphorylation through the mTOR signaling axis.
- The endothelial cell layer remains morphologically intact, suggesting functional impairment without overt injury.
