Tyrosine phosphorylation of platelet derived growth factor beta receptors in coronary artery lesions: implications for vascular remodelling after directional coronary atherectomy and unstable angina pectoris.
BACKGROUND
Growth factors such as platelet derived growth factor (PDGF) have been postulated to be important mediators of neointimal proliferation observed in atherosclerotic plaques and restenotic lesions following coronary interventions. Binding of PDGF to its receptor results in intrinsic receptor tyrosine kinase activation and subsequent cellular migration, proliferation, and vascular contraction.


OBJECTIVE
To investigate whether the concentration of PDGF beta receptor tyrosine phosphorylation obtained from directional coronary atherectomy (DCA) samples correlate with atherosclerotic plaque burden, the ability of diseased vessels to remodel, coronary risk factors, and clinical events.


METHODS
DCA samples from 59 patients and 15 non-atherosclerotic left internal thoracic arteries (LITA) were analysed for PDGF beta receptor tyrosine phosphorylation content by receptor immunoprecipitation and antiphosphotyrosine western blot. The amount of PDGF beta receptor phosphorylation was analysed in relation to angiographic follow up data and clinical variables.


RESULTS
PDGF beta receptor tyrosine phosphorylation in the 59 DCA samples was greater than in the 15 non-atherosclerotic LITA (mean (SD) 0.84 (0.67) v 0.17 (0.08) over a control standard, p < 0.0001). As evaluated by stepwise regression analysis, incorporation of both PDGF beta receptor tyrosine phosphorylation and immediate gain correlated strongly (adjusted r2 = 0.579) with late loss, although PDGF beta receptor tyramine phosphorylation alone correlated poorly with late loss. Multivariate regression analysis of coronary risk factors and clinical events revealed unstable angina as the most significant correlate of PDGF beta receptor tyrosine phosphorylation (F value 20.009, p < 0.0001).


CONCLUSIONS
PDGF beta receptor tyrosine phosphorylation in atherosclerotic lesions is increased compared with non-atherosclerotic arterial tissues. The association of PDGF beta receptor tyrosine phosphorylation with immediate gain strongly correlates with vascular remodelling. PDGF beta receptor tyrosine phosphorylation correlates with unstable angina pectoris.
Abe
J
J
Department of Cardiovascular Biology, Faculty of Medicine, University of Tokyo, Japan.
Deguchi
J
J
Takuwa
Y
Y
Hara
K
K
Ikari
Y
Y
Tamura
T
T
Ohno
M
M
Kurokawa
K
K
D000789:Angina, Unstable / Q000209:etiology; D017225:Atherectomy, Coronary / Q000009:adverse effects*; D003327:Coronary Disease / Q000378:metabolism* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D012008:Recurrence; D012044:Regression Analysis; D012307:Risk Factors; D018709:Statistics, Nonparametric; D014443:Tyrosine / Q000378:metabolism*
D014443:Tyrosine; D017479:Receptors, Platelet-Derived Growth Factor