Different vascular smooth muscle cell apoptosis in the human internal mammary artery and the saphenous vein. Implications for bypass graft disease.
BACKGROUND
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.


RESULTS
Proliferation rates to serum or platelet-derived growth factor (PDGF)-BB were lower in VSMC from MA than SV. Surface expression of PDGF beta-receptor was slightly lower, while that of alpha-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-beta 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.
Frischknecht
Karin
K
Cardiovascular Research, Physiology Institute, University of Zurich, Zurich, Switzerland.
Greutert
Helen
H
Weisshaupt
Christian
C
Kaspar
Mathias
M
Yang
Zhihong
Z
Luscher
Thomas F
TF
Carrel
Thierry P
TP
Tanner
Felix C
FC
D017209:Apoptosis; D000077214:Becaplermin; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D042783:Endothelial Cells; D006083:Graft Occlusion, Vascular / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D006801:Humans; D008323:Mammary Arteries / Q000166:cytology* / Q000201:enzymology / Q000637:transplantation; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011183:Postoperative Complications; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000378:metabolism; D012501:Saphenous Vein / Q000166:cytology* / Q000201:enzymology / Q000637:transplantation; D014654:Vascular Patency
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases