Growth factors released into the coronary circulation after vascular injury promote proliferation of human vascular smooth muscle cells in culture.
OBJECTIVE
This study sought to 1) assess in vivo release of platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) into the coronary circulation after vascular injury in human subjects; and 2) evaluate mitogenic effects of PDGF and bFGF on the patient's own vascular smooth muscle cells (VSMCs).


BACKGROUND
Circumstantial evidence suggests involvement of PDGF and bFGF peptides in the neointimal response to vascular injury. To date, no study has shown biologically active growth factors within the coronary circulation after vascular injury in human subjects.


METHODS
In 18 patients, plasma PDGF AB, platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) levels were measured in coronary sinus blood obtained before and up to 30 min after angioplasty. In five patients undergoing atherectomy, coronary sinus serum was added to cultured VSMCs derived from atherectomy tissue to assess the mitogenic potential of the serum. Mitogenicity attributable to PDGF and bFGF was determined using neutralizing antibodies to these factors. PDGF A, PDGF B and bFGF were localized within the atherectomy tissue using immunocytochemical analysis.


RESULTS
Before angioplasty, PDGF AB, PF4 and beta-TG levels were elevated threefold in patients scheduled for angioplasty compared with those in control patients (p < 0.01). Within 5 min of angioplasty, PDGF AB levels increased twofold and returned toward preangioplasty levels at 30 min; PF4 and beta-TG levels remained elevated. Serum obtained at 30 min after atherectomy showed a sixfold increase in mitogenicity compared with preatherectomy serum (p = 0.01). This increase in mitogenicity was reduced by 20%, 40% and 65% in the presence of neutralizing antibodies to PDGF, bFGF and PDGF + bFGF, respectively. PDGF A, PDGF B and bFGF were visualized within the intima of the atherectomy tissue.


CONCLUSIONS
The change in plasma PDGF level is consistent with first-phase release of PDGF after vascular injury. The increase in mitogenicity of serum suggests that PDGF and bFGF are biologically active.
Caplice
N M
NM
Department of Medicine and Centre for Research in Vascular Biology, University of Queensland, Brisbane, Australia.
Aroney
C N
CN
Bett
J H
JH
Cameron
J
J
Campbell
J H
JH
Hoffmann
N
N
McEniery
P T
PT
West
M J
MJ
D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D017225:Atherectomy, Coronary; D002455:Cell Division; D002478:Cells, Cultured; D003326:Coronary Circulation; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008934:Mitogens; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology; D015539:Platelet Activation; D010978:Platelet Factor 4 / Q000032:analysis; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D001620:beta-Thromboglobulin / Q000032:analysis
D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D001620:beta-Thromboglobulin; D016222:Fibroblast Growth Factor 2; D010978:Platelet Factor 4