Different vascular smooth muscle cell apoptosis in the human internal mammary artery and the saphenous vein: implications for bypass graft disease
Université de Fribourg
- Frischknecht, Karin Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland - Center for Integrative Human Physiology, University of Zürich, Switzerland
- Greutert, Helen Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland - Center for Integrative Human Physiology, University of Zürich, Switzerland
- Weisshaupt, Christian Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland - Center for Integrative Human Physiology, University of Zürich, Switzerland
- Kaspar, Mathias Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland - Center for Integrative Human Physiology, University of Zürich, Switzerland - Cardiology, Cardiovascular Center, University Hospital of Zürich, Switzerland
- Yang, Zhihong Department of Medicine, Division of Physiology, University of Fribourg, Switzerland
- Lüscher, Thomas F. Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland - Center for Integrative Human Physiology, University of Zürich, Switzerland - Cardiology, Cardiovascular Center, University Hospital of Zürich, Switzerland
- Carrel, Thierry P. Clinic for Cardiovascular Surgery, University Hospital of Bern, Switzerland
- Tanner, Felix C. Cardiovascular Research, Physiology Institute, University of Zürich, Switzerland - Center for Integrative Human Physiology, University of Zürich, Switzerland - Cardiology, Cardiovascular Center, University Hospital of Zürich, Switzerland
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26.05.2006
Published in:
- Journal of Vascular Research. - 2006, vol. 43, no. 4, p. 338-346
English
The remarkable patency of internal mammary artery (MA) grafts compared to saphenous vein (SV) grafts has been related to different biological properties of the two blood vessels. We examined whether proliferation and apoptosis of vascular smooth muscle cells (VSMC) from human coronary artery bypass vessels differ according to patency rates. Methods and Results: Proliferation rates to serum or platelet-derived growth factor (PDGF)-BB were lower in VSMC from MA than SV. Surface expression of PDGF β-receptor was slightly lower, while that of α-receptor was slightly higher in MA than SV. Cell cycle distribution, expression of cyclin E, cdk2, p21, p27, p57, and cdk2 kinase activity were identical in PDGF-BB-stimulated cells from MA and SV. However, apoptosis rates were higher in MA than SV determined by lactate dehydrogenase release, DNA fragmentation, and Hoechst 33258 staining. Moreover, caspase inhibitors (Z-VAD-fmk, Boc-D-fmk) abrogated the different proliferation rates of VSMC from MA versus SV. Western blotting and GSK3-β kinase assay revealed lower Akt activity in VSMC from MA versus SV, while total Akt expression was identical. Adenoviral transduction of a constitutively active Akt mutant abrogated the different proliferation rates of VSMC from MA versus SV. Conclusions: Higher apoptosis rates due to lower Akt activity rather than different cell cycle regulation account for the lower proliferation of VSMC from MA as compared to SV. VSMC apoptosis may protect MA from bypass graft disease.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Médecine
- Language
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- English
- Classification
- Medicine
- License
- License undefined
- Identifiers
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- RERO DOC 6383
- DOI 10.1159/000093606
- Persistent URL
- https://folia.unifr.ch/global/documents/300053
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