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

J. Abe, J. Deguchi, Y. Takuwa, K. Hara, Y. Ikari, T. Tamura, M. Ohno, K. Kurokawa

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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. Aims - To investigate whether the concentration of PDGF β 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 β receptor tyrosine phosphorylation content by receptor immunoprecipitation and antiphosphotyrosine western blot. The amount of PDGF β receptor phosphorylation was analysed in relation to angiographic follow up data and clinical variables. Results - PDGF β receptor tyrosine phosphorylation in the 59 DCA samples was greater than in the 15 non- atherosclerotic LITA (mean (SD) 0.84 (0.67) υ 0.17 (0.08) over a control standard, p < 0.0001). As evaluated by stepwise regression analysis, incorporation of both PDGF β receptor tyrosine phosphorylation and immediate gain correlated strongly (adjusted r2 = 0.579) with late loss, although PDGF β 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 β receptor tyrosine phosphorylation (F value 20.009, p < 0.0001). Conclusions - PDGF β receptor tyrosine phosphorylation in atherosclerotic lesions is increased compared with nonatherosclerotic arterial tissues. The association of PDGF β receptor tyrosine phosphorylation with immediate gain strongly correlates with vascular remodelling. PDGF β receptor tyrosine phosphorylation correlates with unstable angina pectoris.

Original languageEnglish (US)
Pages (from-to)400-406
Number of pages7
JournalHeart
Volume79
Issue number4
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

  • Atherosclerosis
  • Directional coronary atherectomy
  • PDGF receptors
  • Restenosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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