Increased expression of genes for platelet-derived growth factor in circulating mononuclear cells of hypercholesterolemic patients.
Platelet-derived growth factor (PDGF) is implicated in the accumulation of smooth muscle cells in atherosclerotic lesions following monocyte migration through the vascular endothelium. We show here a 15- to 20-fold increase in expression of PDGF-A and -B genes (as measured by a quantitative reverse transcription-polymerase chain reaction assay of mRNA concentration) in circulating monocytes of hypercholesterolemic and hyperlipidemic patients compared with normocholesterolemic individuals. Strong positive correlations between PDGF-A and -B mRNA concentrations indicate that the two genes are coordinately regulated in mononuclear cells in both normal and hypercholesterolemic individuals. PDGF gene expression in patients correlates with concentrations of plasma total cholesterol and low-density lipoprotein cholesterol, a proven risk factor for atherosclerosis. Activation of monocyte PDGF expression may be an important component of the atherosclerotic risk associated with raised cholesterol levels and may represent an essential step in the early stages of atherogenesis. However, the marked increases in PDGF mRNA levels in patients with modest hypercholesterolemia compared with normal subjects suggest that other factors are involved. The relationship of monocyte PDGF expression to other atherosclerotic risk factors and to the different stages of atherosclerosis needs to be carefully evaluated.
Billett
M A
MA
Department of Biochemistry, University of Nottingham Medical School, Queen's Medical Centre, UK.
Adbeish
I S
IS
Alrokayan
S A
SA
Bennett
A J
AJ
Marenah
C B
CB
White
D A
DA
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D011973:Receptors, LDL / Q000235:genetics
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011973:Receptors, LDL