Local adenovirus-mediated transfer of C-type natriuretic peptide suppresses vascular remodeling in porcine coronary arteries in vivo

OBJECTIVE This study was designed to examine whether or not adenovirus-medi ated gene transfer of C-type natriuretic peptide (CNP) can prevent coronary restenotic changes after balloon injury in pigs in vivo. BACKGROUND Gene therapy to prevent restenosis after percutaneous translumin al coronary angioplasty (PTCA) might be useful but requires a method applic able for in vivo gene delivery into the coronary artery as well as the effi cient vector encoding a potent antiproliferative substance. We tested wheth er the adenovirus-mediated gene transfer of CNP by use of an infiltrator an gioplasty balloon catheter (IABC) might prevent the coronary restenotic cha nges after balloon injury. METHODS Balloon angioplasty was performed in the left anterior descending a nd the left circumflex coronary artery in pigs. Immediately after the ballo on injury, adenovirus solution encoding either CNP (AdCACNP) or beta-galact osidase (AdCALacZ) gene was injected with IABC into the balloon-injured cor onary segments. Expression of CNP was assessed by immunohistochemical stain ing and cyclic guanosine 3',5'-monophosphate (cGMP) measurement. Coronary r estenotic changes were evaluated by both angiographic and histological exam inations. RESULTS CNP was highly expressed in the media and the adventitia of the cor onary artery at the AdCACNP-transfected but not at the AdCALacZ-transfected segment. In the AdCALacZ-transfeaed segment, vascular cGMP levels tended t o be reduced as compared with the untreated segment, whereas in the AdCACNP -transfected segment, vascular cGMP levels were restored. Angiographic coro nary stenosis was significantly less at the AdCACNP-transfected than at the AdCALacZ-transfected segment. Histological examination revealed that this was achieved primarily by the marked inhibition of the geometric remodeling of the coronary artery by the CNP gene transfer. CONCLUSIONS Adenovirus-mediated CNP gene transfer with the IABC system may be a useful gene therapy to prevent restenosis after PTCA in vivo. (C) 2000 by the American College of Cardiology.