From Cardiovascular Research (Z.Y., B.S.O., T.F.L.), Institute for
Physiology, University Zürich-Irchel, Switzerland; Cardiology (F.J.),
Cardiovascular and Thoracic Surgery (T.C., B.K.), Inselspital Bern,
Switzerland; and Cardiology (Z.Y., B.S.O., T.F.L.), University Hospital
Zürich, Switzerland.
Correspondence to Thomas F. Lüscher, MD, Professor and Head of Cardiology, University Hospital, CH-8091 Zürich, Switzerland.
Background—Internal mammary artery
(IMA) bypass grafts have a higher patency than saphenous vein (SV)
grafts. Intimal hyperplasia of SV grafts is due to smooth muscle cell
(SMC) proliferation and migration. We hypothesized that different SMC
growth activity exists in IMA and SV, which may explain the different
patencies of arterial and venous grafts.
Methods and Results—SMCs were isolated from IMA and SV by explant
culture and stimulated with serum or platelet-derived growth
factor-BB (PDGF-BB). Cell growth was analyzed by explant
outgrowth rate, 3H-thymidine incorporation, or cell
counting. PDGF receptor expression and
autophosphorylation, regulation of
mitogen-activated protein kinases (MAPKs), and cyclin-dependent
kinase inhibitors (p27Kip1 and
p21Cip1) were analyzed by molecular techniques. SMC
outgrowth from explants by serum (20%) over a 20-day period was more
pronounced in SV (37±5%) than in IMA (4±3%; P<.001)
of the same patients. Serum (10%) increased cell number more rapidly
in SV (2x104/well to 18±4x104/well;
P<.05) than in IMA (2x104/well to
9±4x104/well; P<.05) over an 8-day
period. PDGF-BB (0.01 to 10 ng/mL) stimulated 3H-thymidine
incorporation (1347±470% above control levels) and increased cell
number in SV (2x104/well to 5±1x104/well;
P<.05) but not in IMA. PDGF
Conclusions—SMCs from SVs exhibit enhanced proliferation compared
with IMA in spite of functional growth factor receptor expression and
MAPK activation. However, PDGF increased MAPK protein level only in SV
and downregulated cell cycle inhibitor
(p27Kip1) more potently in SV than in IMA. This may explain
the resistance to growth stimuli of IMA SMCs and may contribute to the
longer patency of arterial versus venous grafts.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Different Proliferative Properties of Smooth Muscle Cells of Human Arterial and Venous Bypass Vessels
Role of PDGF Receptors, Mitogen-Activated Protein Kinase, and Cyclin-Dependent Kinase Inhibitors
- and ß-receptors were
similarly expressed and were activated in both SV and IMA.
PDGF-BB induced a similar MAPK activation (kinetics and maximal
activity) in both SV and IMA cells but increased MAPK protein level
only in SV. Furthermore, PDGF-BB markedly downregulated the cell cycle
inhibitor p27Kip1 in SV, but this was much less
pronounced in IMA.
Key Words: muscle, smooth • vessels • cells • growth substances • enzymes
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