Enhanced migratory activity of vascular smooth muscle cells with high expression of platelet-derived growth factor A and B.
Proliferation and migration of vascular smooth muscle cells (SMCs) are major events in atherogenesis. It is known that platelet-derived growth factor (PDGF) stimulates both of these processes in a paracrine fashion, whereas autocrine stimulation has been shown only for proliferation. The aim of this study was to investigate the influence of PDGF expression in SMCs on migratory activity of these cells. SMCs were cultivated from the vascular tissue of 23 patients. Cellular motility was analyzed by a computer-assisted motion analysis system; 54 images per sample, obtained during an observation period of eighteen hours, were analyzed. PDGF-A and PDGF-B mRNA levels were determined by quantitative polymerase chain reaction (PCR) following reverse transcription. To quantitate mRNA content of SMCs, the authors coamplified cDNA copies of mRNA from cells and from a synthetic reference RNA in the same reaction vessel. Cells derived from atherosclerotic lesions produced a 1.6-fold increase of PDGF-A (P < 0.05) and a 5-fold increase of PDGF-B mRNA (P < 0.05) as compared with those from normal vessels. The migratory velocity (range 11.1-49.2 microns/hr) was independent of PDGF-A and PDGF-B mRNA expression. A significant correlation between levels of PDGF-A mRNA and PDGF-B mRNA and the degree of directional changes of SMCs on the covered track (klinokinesis) was found (P < 0.05).


CONCLUSIONS
PDGF-A and PDGF-B mRNA expression is significantly correlated with positive klinokinesis without affecting migratory velocity. This finding reflects enhanced migratory activity of SMCs. Besides its known mitogenic effects, the authors present evidence that PDGF may act as an autocrine motogen* in SMCs.
Köster
R
R
Department of Internal Medicine, University of Munich, Germany.
Windstetter
U
U
Uberfuhr
P
P
Baumann
G
G
Nikol
S
S
Höfling
B
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D015139:Blotting, Southern; D002465:Cell Movement; D002478:Cells, Cultured; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D014158:Transcription, Genetic
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; C075278:platelet-derived growth factor A