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CLINICAL STUDIES

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

^a Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Manuscript received June 7, 1999; revised manuscript received October 15, 1999, accepted November 19, 1999.

Reprint requests and correspondence: Dr. Hiroaki Shimokawa, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
shimo{at}cardiol.med.kyushu-u.ac.jp

OBJECTIVE

This study was designed to examine whether or not adenovirus-mediated 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 transluminal coronary angioplasty (PTCA) might be useful but requires a method applicable for in vivo gene delivery into the coronary artery as well as the efficient vector encoding a potent antiproliferative substance. We tested whether the adenovirus-mediated gene transfer of CNP by use of an infiltrator angioplasty balloon catheter (IABC) might prevent the coronary restenotic changes after balloon injury.

METHODS

Balloon angioplasty was performed in the left anterior descending and the left circumflex coronary artery in pigs. Immediately after the balloon injury, adenovirus solution encoding either CNP (AdCACNP) or ß-galactosidase (AdCALacZ) gene was injected with IABC into the balloon-injured coronary segments. Expression of CNP was assessed by immunohistochemical staining and cyclic guanosine 3',5'-monophosphate (cGMP) measurement. Coronary restenotic changes were evaluated by both angiographic and histological examinations.

RESULTS

CNP was highly expressed in the media and the adventitia of the coronary artery at the AdCACNP-transfected but not at the AdCALacZ-transfected segment. In the AdCALacZ-transfected segment, vascular cGMP levels tended to be reduced as compared with the untreated segment, whereas in the AdCACNP-transfected segment, vascular cGMP levels were restored. Angiographic coronary 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.

Abbreviations and Acronyms   AdCACNP = adenovirus vector encoding CNP   AdCALacZ = adenovirus vector encoding b-galactosidase   cGMP = cyclic guanosine 3’,5’-monophosphate   CNP = C-type natriuretic peptide   EEL = external elastic lamina   IABC = infiltrator angioplasty balloon catheter   IEL = internal elastic lamina   LAD = left anterior descending coronary artery   LCX = left circumflex coronary artery   NO = nitric oxide   NPR-B = natriuretic peptide-B   PTCA = percutaneous transluminal coronary angioplasty   VSMC = vascular smooth muscle cells

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