Local adenovirus-mediated transfer of C-type natriuretic peptide suppresses vascular remodeling in porcine coronary arteries in vivo
Kunio Morishige, MDa,
Hiroaki Shimokawa, MDa,
Tohru Yamawaki, MDa,
Kenji Miyata, MDa,
Yasuhiro Eto, MDa,
Tadashi Kandabashi, MDa,
Kenji Yogo, PhDa,
Taiki Higo, MDa,
Kensuke Egashira, MDa,
Hikaru Ueno, MDa and
Akira Takeshita, MD, FACCa
a Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Figure 1 Experimental protocol in the present study. AdCACNP was transfected to the balloon-injured site for LAD (n = 8) or LCX (n = 7), whereas AdCALacZ was transfected to the remaining balloon-injured site in a randomized manner.
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Figure 2 Immunohistochemical staining of the porcine coronary artery one week after the adenovirus transfection in vivo. A, Balloon-injured coronary segment with AdCALacZ transfection (double staining with X-gal and hematoxylin-eosin methods, magnification x40). B and C, Balloon-injured coronary segments with AdCACNP transfection stained with anti-CNP antibody (brown) (B) and nonimmune IgG (C).
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Figure 3 cGMP levels in balloon-injured porcine coronary arteries. cGMP levels (pmol/mg protein) one week after the gene transfer are shown for normal coronary arteries (Normal), injured coronary arteries transfected with AdCALacZ (LacZ) or AdCACNP (CNP). *p < 0.05 vs. AdCALacZ-transfected site.
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Figure 4 Coronary arteriograms after intracoronary administration of nitroglycerin (10 µg/kg) in a pig before (A) and three weeks after (B) the gene transfer in vivo. The white arrow indicates the site transfected with AdCALacZ (LacZ), and the black arrow indicates the site transfected with AdCACNP (CNP).
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Figure 5 Quantitative analysis of coronary diameter three weeks after the gene transfer in vivo (n = 6). All individual data are plotted. LacZ: AdCALacZ-transfected site; CNP: AdCACNP-transfected site.
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Figure 6 Histology of the coronary artery segments transfected with AdCALacZ (A) or AdCACNP (C) after the angioplasty and of the untreated segments adjacent to AdCALacZ-transfected segment (B) and AdCACNP-transfected segment (D). Vascular remodeling is suppressed at the AdCACNP-transfected segment compared with the AdCALacZ-transfected segment. Note that the extent of the fractured IEL caused by angioplasty was comparable between the AdCALacZ- and the AdCACNP-transfected sites.
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Figure 7 Changes of the cross-sectional areas of porcine coronary arteries three weeks after the gene transfer. The reduction of the cross-sectional area at the treated segment is expressed in percent change compared with the mean cross-sectional area of the adjacent proximal and distal normal coronary segments. EEL, external elastic lamina area; IEL, internal elastic lamina area; Lumen, lumen area; LacZ, AdCALacZ-transfected site; CNP, AdCACNP-transfected site. *p < 0.05 vs. AdCALacZ-transfected site.
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Figure 8 Correlation between the extent of angiographic coronary stenosis and that of histological lumen narrowing. There was a significant exponential correlation between the two values.
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