Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques.
We studied death of human vascular smooth muscle cells derived from coronary plaques and normal coronary arteries and aorta. Cells from normal arteries underwent death only upon removal of serum growth factors. In contrast, plaque-derived cells died even in high serum conditions, and death increased after serum withdrawal. Death was characteristically by apoptosis in both normal and plaque-derived cells, as determined by time-lapse videomicroscopy, electron microscopy, and DNA fragmentation patterns. IGF-1 and PDGF were identified as potent survival factors in serum, whereas EGF and basic fibroblast growth factor had little effect. Stable expression of bcl-2, a protooncogene that regulates apoptosis in other cell lines, protected smooth muscle cells from apoptosis, although there was no detectable difference in endogenous bcl-2 expression between cells from plaques or normal vessels. We conclude that apoptosis of human vascular smooth muscle cells is regulated by both specific gene products and local cytokines acting as survival factors. Apoptosis may therefore regulate cell mass in the normal arterial wall and the higher rates of apoptosis seen in plaque smooth muscle cells may ultimately contribute to plaque rupture and breakdown and thus to the clinical sequelae of atherosclerosis.
Bennett
M R
MR
Department of Pathology, University of Washington, Seattle 98195, USA.
Evan
G I
GI
Schwartz
S M
SM
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001013:Aorta, Thoracic / Q000166:cytology* / Q000473:pathology / Q000503:physiopathology; D017209:Apoptosis / Q000187:drug effects; D001161:Arteriosclerosis / Q000473:pathology* / Q000503:physiopathology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000473:pathology / Q000503:physiopathology; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D012016:Reference Values
D006133:Growth Substances; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011505:Protein-Tyrosine Kinases