TY - JOUR
T1 - Enhanced angiotensin II degradation in porcine coronary neointimal hyperplasia induced by stent implantation
AU - Van der Giessen, W. J.
AU - Danser, A. H.J.
AU - Van Beusekom, H. M.M.
AU - Derkx, F. H.M.
AU - Verdouw, P. D.
AU - Lamers, J. M.J.
AU - Serruys, P. W.
PY - 1992
Y1 - 1992
N2 - Background: Angiotensin II (Ang II) has been proposed as a modulator of growth factor responses in the arterial wall. Employing a model of stent- induced neointimal hyperplasia, we studied angiotensin I (Ang I) elimination. Methods: Balloon-expandable radiopaque stents (n=6) were implanted in coronary arteries of pigs. After 3 months, the stented and nonstented (control) vessels were studied in vitro for their conversion of radiolabeled 125I-Ang I to 125I-Ang II in the presence or absence of captopril. Conversion was also studied after removal of the endothelium. Results: Immunocytochemistry confirmed the presence of endothelium covering the neointima. Stented vessels metabolized 125I-Ang I faster and released less 125I-Ang II than normal arteries. 125I-Ang I formation could be completely blocked by captopril, but only up to 75% by removal of the endothelium. Determination of the rate constants for elimination of 125I- Ang I revealed that the reduced release of 125I-Ang II appeared not to be due to decreased conversion by angiotensin-converting enzyme in stented vessels, but merely to increased degradation. Conclusions: Porcine coronary arteries up to 3 months after stent implantation release significantly less 125I-Ang II upon challenge with 125I-Ang I. A higher degradation of 125I-Ang II in the stented coronary arterial wall may explain this finding. Enhanced degradation of pro-, but likely also of antiproliferative, peptide growth factors locally in the vessel wall may further complicate our understanding of neointimal proliferation after arterial damage.
AB - Background: Angiotensin II (Ang II) has been proposed as a modulator of growth factor responses in the arterial wall. Employing a model of stent- induced neointimal hyperplasia, we studied angiotensin I (Ang I) elimination. Methods: Balloon-expandable radiopaque stents (n=6) were implanted in coronary arteries of pigs. After 3 months, the stented and nonstented (control) vessels were studied in vitro for their conversion of radiolabeled 125I-Ang I to 125I-Ang II in the presence or absence of captopril. Conversion was also studied after removal of the endothelium. Results: Immunocytochemistry confirmed the presence of endothelium covering the neointima. Stented vessels metabolized 125I-Ang I faster and released less 125I-Ang II than normal arteries. 125I-Ang I formation could be completely blocked by captopril, but only up to 75% by removal of the endothelium. Determination of the rate constants for elimination of 125I- Ang I revealed that the reduced release of 125I-Ang II appeared not to be due to decreased conversion by angiotensin-converting enzyme in stented vessels, but merely to increased degradation. Conclusions: Porcine coronary arteries up to 3 months after stent implantation release significantly less 125I-Ang II upon challenge with 125I-Ang I. A higher degradation of 125I-Ang II in the stented coronary arterial wall may explain this finding. Enhanced degradation of pro-, but likely also of antiproliferative, peptide growth factors locally in the vessel wall may further complicate our understanding of neointimal proliferation after arterial damage.
UR - https://www.scopus.com/pages/publications/0026697829
M3 - Article
AN - SCOPUS:0026697829
SN - 0954-6928
VL - 3
SP - 730
EP - 737
JO - Coronary Artery Disease
JF - Coronary Artery Disease
IS - 8
ER -