Vascular Endothelial Growth Factor Enhances Cardiac Allograft Arteriosclerosis

Autor: Rainer Krebs, Eva M. Aaltola, Petri Koskinen, Pekka Häyry, Antti I. Nykänen, Karl B. Lemström, Jeanette Wood, Seppo Ylä-Herttuala, Roope Sihvola, Kari Alitalo, Jussi Tikkanen
Rok vydání: 2002
Předmět:
Graft Rejection
Vascular Endothelial Growth Factor A
Pathology
Transplantation
Heterotopic
genetic structures
Arteriosclerosis
Pyridines
Angiogenesis
Angiogenesis Inhibitors
Endothelial Growth Factors
chemistry.chemical_compound
Myocyte
In Situ Hybridization
Lymphokines
Vascular Endothelial Growth Factors
Graft Survival
Immunohistochemistry
Vascular endothelial growth factor
Vascular endothelial growth factor A
Acute Disease
Disease Progression
Rabbits
medicine.symptom
Cardiology and Cardiovascular Medicine
medicine.medical_specialty
Gene Transfer
Horizontal
Inflammation
Transfection
Physiology (medical)
medicine
Animals
Receptors
Growth Factor
RNA
Messenger
business.industry
Vascular disease
Macrophages
Myocardium
Lymphokine
Receptor Protein-Tyrosine Kinases
Rats
Inbred Strains
medicine.disease
Rats
Disease Models
Animal
Receptors
Vascular Endothelial Growth Factor
chemistry
Chronic Disease
Immunology
Leukocytes
Mononuclear
Heart Transplantation
Phthalazines
business
Zdroj: Circulation. 105:2524-2530
ISSN: 1524-4539
0009-7322
DOI: 10.1161/01.cir.0000016821.76177.d2
Popis: 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.
Databáze: OpenAIRE
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