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

doi:10.1136/hrt.79.4.400

Heart 1998;79:400-406; doi:10.1136/hrt.79.4.400

Heart 1998;79:400-406 ( April )

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

J Abe,^a J Deguchi,^a Y Takuwa,^a K Hara,^b Y Ikari,^b T Tamura,^b M Ohno,^c K Kurokawa^c

^a Department of Cardiovascular Biology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan, ^b Department of Cardiology, Mitsui Memorial Hospital, KandaIzumicyo, Tokyo 111, Japan, ^c Departments of Internal Medicine, Faculty of Medicine, University of Tokyo

Correspondence to: Dr Takuwa. email: yohtakwa{at}m.u-tokyo.ac.jp

Accepted for publication 10 October 1997

Background $---$ Growth factors such as platelet derived growth factor (PDGF) have been postulated to be important mediators of neointimalproliferation observed in atherosclerotic plaques and restenoticlesions following coronary interventions. Binding of PDGF to itsreceptor results in intrinsic receptor tyrosine kinase activationand subsequent cellular migration, proliferation, and vascularcontraction.
Aims $---$ To investigate whether the concentration of PDGF $beta$ receptor tyrosine phosphorylation obtained from directional coronary atherectomy(DCA) samples correlate with atherosclerotic plaque burden, theability of diseased vessels to remodel, coronary risk factors,and clinicalevents.
Methods $---$ DCA samples from 59 patients and 15 non-atherosclerotic left internal thoracic arteries (LITA) were analysed for PDGF $beta$ receptortyrosine phosphorylation content by receptor immunoprecipitationand antiphosphotyrosine western blot. The amount of PDGF $beta$ receptorphosphorylation was analysed in relation to angiographic followup data and clinicalvariables.
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 ofboth PDGF $beta$ receptor tyrosine phosphorylation and immediate gaincorrelated strongly (adjusted r² = 0.579) with late loss, although PDGF $beta$ receptor tyramine phosphorylationalone correlated poorly with late loss. Multivariate regressionanalysis of coronary risk factors and clinical events revealedunstable angina as the most significant correlate of PDGF $beta$ receptortyrosine phosphorylation (F value 20.009, p < 0.0001).
Conclusions $---$ PDGF $beta$ receptor tyrosine phosphorylation in atherosclerotic lesions is increased compared with non-atherosclerotic arterialtissues. The association of PDGF $beta$ receptor tyrosine phosphorylationwith immediate gain strongly correlates with vascular remodelling.PDGF $beta$ receptor tyrosine phosphorylation correlates with unstableanginapectoris.

Keywords: PDGF receptors; atherosclerosis; directional coronary atherectomy; restenosis

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Tyrosine phosphorylation of platelet derived growth factor receptors in coronary artery lesions: implications for vascular remodelling after directional coronary atherectomy and unstable angina pectoris