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.
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 mouseVEGF(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.
Authors: Monika Edelbauer; Dipak Datta; Ingrid H C Vos; Aninda Basu; Maria P Stack; Marlies E J Reinders; Masayuki Sho; Katiana Calzadilla; Peter Ganz; David M Briscoe Journal: Blood Date: 2010-06-10 Impact factor: 22.113
Authors: Jiasheng Zhang; Teresa Silva; Timur Yarovinsky; Thomas D Manes; Sina Tavakoli; Lei Nie; George Tellides; Jordan S Pober; Jeffrey R Bender; Mehran M Sadeghi Journal: Circ Res Date: 2010-06-10 Impact factor: 17.367
Authors: Jiasheng Zhang; Mahmoud Razavian; Sina Tavakoli; Lei Nie; George Tellides; Joseph M Backer; Marina V Backer; Jeffrey R Bender; Mehran M Sadeghi Journal: Arterioscler Thromb Vasc Biol Date: 2012-06-21 Impact factor: 8.311
Authors: Johannes Wedel; Sarah Bruneau; Nora Kochupurakkal; Leo Boneschansker; David M Briscoe Journal: Curr Opin Organ Transplant Date: 2015-02 Impact factor: 2.640