Enhanced angiotensin II degradation in porcine coronary neointimal hyperplasia induced by stent implantation

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.