Angiogenesis, vascular endothelial growth factor and platelet-derived growth factor-BB expression, iron deposition, and oxidation-specific epitopes in stented human coronary arteries
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Angiogenesis, vascular endothelial growth factor and platelet-derived growth factor-BB expression, iron deposition, and oxidation-specific epitopes in stented human coronary arteries. / Bräsen, J H; Kivelä, A; Röser, K; Rissanen, T T; Niemi, M; Luft, F C; Donath, K; Ylä-Herttuala, S.
In: ARTERIOSCL THROM VAS, Vol. 21, No. 11, 11.2001, p. 1720-6.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Angiogenesis, vascular endothelial growth factor and platelet-derived growth factor-BB expression, iron deposition, and oxidation-specific epitopes in stented human coronary arteries
AU - Bräsen, J H
AU - Kivelä, A
AU - Röser, K
AU - Rissanen, T T
AU - Niemi, M
AU - Luft, F C
AU - Donath, K
AU - Ylä-Herttuala, S
PY - 2001/11
Y1 - 2001/11
N2 - Pathogenesis of in-stent restenosis remains poorly understood because information from human histopathologic studies is scarce. We used an improved saw-grinding and cutting method on methacrylate-embedded samples containing metal stents, which allows in situ hybridization and immunohistochemical analysis of in-stent restenosis. Twenty-one samples were collected 3 hours to 3 years after stenting from 6 patients aged 36 to 81 years. Except in very early samples collected within hours after the stent deployment, neovascularization was present in all segments studied. At advanced stages, extensive neovascularization was located mainly at the luminal side of the stent struts and was only rarely accompanied by inflammatory cells. The neovessels colocalized with vascular endothelial growth factor (VEGF)-A mRNA and protein expression as well as with iron deposits and oxidation-specific epitopes, which imply the presence of chronic oxidative stress. VEGF-A expression was detected in the same areas containing macrophages, endothelial cells, and, to a lesser extent, smooth muscle cells, which also showed platelet-derived growth factor-BB expression. We conclude that in-stent restenosis features neovascularization, VEGF-A and platelet-derived growth factor-BB expression, and iron deposition, which is most probably derived from microhemorrhages. These mechanisms may play an important role in the development of neointimal thickening and could provide useful targets for the prevention and treatment of in-stent restenosis.
AB - Pathogenesis of in-stent restenosis remains poorly understood because information from human histopathologic studies is scarce. We used an improved saw-grinding and cutting method on methacrylate-embedded samples containing metal stents, which allows in situ hybridization and immunohistochemical analysis of in-stent restenosis. Twenty-one samples were collected 3 hours to 3 years after stenting from 6 patients aged 36 to 81 years. Except in very early samples collected within hours after the stent deployment, neovascularization was present in all segments studied. At advanced stages, extensive neovascularization was located mainly at the luminal side of the stent struts and was only rarely accompanied by inflammatory cells. The neovessels colocalized with vascular endothelial growth factor (VEGF)-A mRNA and protein expression as well as with iron deposits and oxidation-specific epitopes, which imply the presence of chronic oxidative stress. VEGF-A expression was detected in the same areas containing macrophages, endothelial cells, and, to a lesser extent, smooth muscle cells, which also showed platelet-derived growth factor-BB expression. We conclude that in-stent restenosis features neovascularization, VEGF-A and platelet-derived growth factor-BB expression, and iron deposition, which is most probably derived from microhemorrhages. These mechanisms may play an important role in the development of neointimal thickening and could provide useful targets for the prevention and treatment of in-stent restenosis.
KW - Adult
KW - Aged
KW - Coronary Restenosis
KW - Coronary Thrombosis
KW - Coronary Vessels
KW - Endothelial Growth Factors
KW - Epitopes
KW - Female
KW - Humans
KW - Immunohistochemistry
KW - In Situ Hybridization
KW - Iron
KW - Kinetics
KW - Male
KW - Methylmethacrylate
KW - Middle Aged
KW - Neovascularization, Pathologic
KW - Oxidative Stress
KW - Platelet-Derived Growth Factor
KW - Proto-Oncogene Proteins c-sis
KW - RNA
KW - Stents
KW - Transcription, Genetic
KW - Vascular Endothelial Growth Factor A
KW - Case Reports
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
M3 - SCORING: Journal article
C2 - 11701456
VL - 21
SP - 1720
EP - 1726
JO - ARTERIOSCL THROM VAS
JF - ARTERIOSCL THROM VAS
SN - 1079-5642
IS - 11
ER -
