Vascular endothelial growth factor enhances cardiac allograft arteriosclerosis.

Abstract:

BACKGROUND:Cardiac allograft arteriosclerosis is a complex process of alloimmune response, chronic inflammation, and smooth muscle cell proliferation that includes cross talk between cytokines and growth factors. METHODS AND RESULTS:Our results in rat cardiac allografts established alloimmune response as an alternative stimulus capable of inducing vascular endothelial growth factor (VEGF) mRNA and protein expression in cardiomyocytes and graft-infiltrating mononuclear inflammatory cells, which suggests that these cells may function as a source of VEGF to the cells of coronary arteries. Linear regression analysis of these allografts with different stages of arteriosclerotic lesions revealed a strong correlation between intragraft VEGF protein expression and the development of intimal thickening, whereas blockade of signaling downstream of VEGF receptor significantly reduced arteriosclerotic lesions. In addition, in cholesterol-fed rabbits, intracoronary perfusion of cardiac allografts with a clinical-grade adenoviral vector that encoded mouse VEGF(164) enhanced the formation of arteriosclerotic lesions, possibly secondary to increased intragraft influx of macrophages and neovascularization in the intimal lesions. CONCLUSIONS:Our findings suggest a positive regulatory role between VEGF and coronary arteriosclerotic lesion formation in the allograft cytokine microenvironment.

journal_name

Circulation

journal_title

Circulation

authors

Lemström KB,Krebs R,Nykänen AI,Tikkanen JM,Sihvola RK,Aaltola EM,Häyry PJ,Wood J,Alitalo K,Ylä-Herttuala S,Koskinen PK

doi

10.1161/01.cir.0000016821.76177.d2

subject

Has Abstract

pub_date

2002-05-28 00:00:00

pages

2524-30

issue

21

eissn

0009-7322

issn

1524-4539

journal_volume

105

pub_type

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