(Circulation. 1997;96:2272-2279.)
© 1997 American Heart Association, Inc.
Articles |
Local Expression of C-Type Natriuretic Peptide Markedly Suppresses Neointimal Formation in Rat Injured Arteries Through an Autocrine/Paracrine Loop
From the Molecular Cardiology Unit, Department of Cardiology, Kyushu University School of Medicine, Fukuoka (H.U., A.T.); the Department of Medicine II, Chiba University School of Medicine (A.H., N.M., Y.S.); the Suntory Institute for Biomedical Research, Osaka (M.F.); and the National Cardiovascular Center Research Institute, Osaka (K.K.), Japan.
Correspondence to Hikaru Ueno, MD, PhD, Department of Cardiology, Kyushu University School of Medicine, Fukuoka, 812-82 Japan. E-mail ueno{at}cardiol.med.kyushu-u.ac.jp
Background In vivo gene transfer into injured arteries may provide a new means to facilitate molecular understanding of and to treat the intractable fibroproliferative arterial diseases. Selection of an optimal molecule to be transferred will be a key to successful gene therapy in the future. We tested the hypothesis that a secreted multifactorial molecule should act more efficiently through an autocrine/paracrine loop to suppress neointimal formation elicited in injured arteries than a simple growth-inhibiting molecule that might be expressed inside cells.
Methods and Results We constructed an adenoviral vector (AdCACNP) expressing C-type natriuretic peptide (CNP), a secreted stimulator of membrane-bound guanyl cyclase. AdCACNP directs cells to secrete large quantities of biologically active CNP. Serum-stimulated DNA synthesis and cell proliferation were only moderately suppressed in arterial smooth muscle cells infected with AdCACNP in vitro. However, when AdCACNP was applied to balloon-injured rat carotid arteries in vivo, neointimal formation was markedly reduced (90% reduction) in an infection-site–specific manner without an increase in plasma CNP level.
Conclusions Our results showed that CNP, a secreted multifactorial molecule, was indeed effective in suppressing fibroproliferative response in injured arteries and suggest that the potent antiproliferation effect may not be the most critical factor for the effective suppression of neointimal formation. An adenovirus-mediated expression of CNP could be an effective and site-specific form of molecular intervention in proliferative arterial diseases.
Key Words: natriuretic peptides • viruses • genes • restenosis
This article has been cited by other articles:
 |
|
 |
|
  T. O. Peltonen, P. Taskinen, Y. Soini, J. Rysa, J. Ronkainen, P. Ohtonen, J. Satta, T. Juvonen, H. Ruskoaho, and H. Leskinen Distinct Downregulation of C-Type Natriuretic Peptide System in Human Aortic Valve Stenosis Circulation, September 11, 2007; 116(11): 1283 - 1289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. N. Barber, M. Kanagasundaram, C. R. Anderson, L. M. Burrell, and R. L. Woods Vascular neutral endopeptidase inhibition improves endothelial function and reduces intimal hyperplasia Cardiovasc Res, July 1, 2006; 71(1): 179 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Rahmutula and D. G. Gardner C-Type Natriuretic Peptide Down-Regulates Expression of Its Cognate Receptor in Rat Aortic Smooth Muscle Cells Endocrinology, November 1, 2005; 146(11): 4968 - 4974. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Kelsall, A. H. Chester, M. Amrani, and D. R.J. Singer C-Type Natriuretic Peptide Relaxes Human Coronary Artery Bypass Grafts Preconstricted by Endothelin-1 Ann. Thorac. Surg., October 1, 2005; 80(4): 1347 - 1351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Kairuz, M. N. Barber, C. R. Anderson, M. Kanagasundaram, G. R. Drummond, and R. L. Woods C-type natriuretic peptide (CNP) suppresses plasminogen activator inhibitor-1 (PAI-1) in vivo Cardiovasc Res, June 1, 2005; 66(3): 574 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Chandiwal, V. Balasubramanian, Z. K. Baldwin, M. S. Conte, and L. B. Schwartz Gene Therapy for the Extension of Vein Graft Patency: A Review Vascular and Endovascular Surgery, January 1, 2005; 39(1): 1 - 14. [Abstract] [PDF]
|
|
|
|
 |
|
 D. Rahmutula, J. Cui, S. Chen, and D. G. Gardner Transcriptional Regulation of Type B Human Natriuretic Peptide Receptor Gene Promoter: Dependence on Sp1 Hypertension, September 1, 2004; 44(3): 283 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Schachner, Y. Zou, A. Oberhuber, T. Mairinger, A. Tzankov, G. Laufer, H. Ott, and J. Bonatti Perivascular application of C-type natriuretic peptide attenuates neointimal hyperplasia in experimental vein grafts Eur. J. Cardiothorac. Surg., April 1, 2004; 25(4): 585 - 590. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. I. McFarlane, N. Winer, and J. R. Sowers Role of the Natriuretic Peptide System in Cardiorenal Protection Arch Intern Med, December 8, 2003; 163(22): 2696 - 2704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Wu, F. Wu, J. Pan, J. Morser, and Q. Wu Furin-mediated Processing of Pro-C-type Natriuretic Peptide J. Biol. Chem., July 3, 2003; 278(28): 25847 - 25852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Surendran and T. C. Simon CNP gene expression is activated by Wnt signaling and correlates with Wnt4 expression during renal injury Am J Physiol Renal Physiol, April 1, 2003; 284(4): F653 - F662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-Y. Qian, A. Haruno, Y. Asada, T. Nishida, Y. Saito, T. Matsuda, and H. Ueno Local Expression of C-Type Natriuretic Peptide Suppresses Inflammation, Eliminates Shear Stress-Induced Thrombosis, and Prevents Neointima Formation Through Enhanced Nitric Oxide Production in Rabbit Injured Carotid Arteries Circ. Res., November 29, 2002; 91(11): 1063 - 1069. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Abbey and L. R. Potter Vasopressin-dependent Inhibition of the C-type Natriuretic Peptide Receptor, NPR-B/GC-B, Requires Elevated Intracellular Calcium Concentrations J. Biol. Chem., November 1, 2002; 277(45): 42423 - 42430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Seki, N. Hashimoto, Y. Suzuki, S. Mori, K. Amano, and Y. Saito Role of Src Homology 2-Containing Tyrosine Phosphatase 2 on Proliferation of Rat Smooth Muscle Cells Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1081 - 1085. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.R Kalra, S.D Anker, A.D Struthers, and A.J.S Coats The role of C-type natriuretic peptide in cardiovascular medicine Eur. Heart J., June 2, 2001; 22(12): 997 - 1007. [PDF]
|
|
|
|
|
|
K. Doi, T. Ikeda, H. Itoh, K. Ueyama, K. Hosoda, Y. Ogawa, J. Yamashita, T.-H. Chun, M. Inoue, K. Masatsugu, et al. C-Type Natriuretic Peptide Induces Redifferentiation of Vascular Smooth Muscle Cells With Accelerated Reendothelialization Arterioscler Thromb Vasc Biol, June 1, 2001; 21(6): 930 - 936. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Atsuchi, T. Nishida, K. Marutsuka, Y. Asada, Y. Kamikubo, A. Takeshita, and H. Ueno Combination of a Brief Irrigation With Tissue Factor Pathway Inhibitor (TFPI) and Adenovirus-Mediated Local TFPI Gene Transfer Additively Reduces Neointima Formation in Balloon-Injured Rabbit Carotid Arteries Circulation, January 30, 2001; 103(4): 570 - 575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Meyerson, C. L. Skelly, M. A. Curi, and L. B. Schwartz Gene Therapy for Cardiovascular Disease Seminars in Cardiothoracic and Vascular Anesthesia, November 1, 2000; 4(4): 289 - 300. [Abstract] [PDF]
|
|
|
|
 |
|
 K. Morishige, H. Shimokawa, T. Yamawaki, K. Miyata, Y. Eto, T. Kandabashi, K. Yogo, T. Higo, K. Egashira, H. Ueno, et al. Local adenovirus-mediated transfer of C-type natriuretic peptide suppresses vascular remodeling in porcine coronary arteries in vivo J. Am. Coll. Cardiol., March 15, 2000; 35(4): 1040 - 1047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sinnaeve, O. Varenne, D. Collen, and S. Janssens Gene therapy in the cardiovascular system: an update Cardiovasc Res, December 1, 1999; 44(3): 498 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kanaki, H. Bujo, S. Hirayama, I. Ishii, N. Morisaki, W. J. Schneider, and Y. Saito Expression of LR11, a Mosaic LDL Receptor Family Member, Is Markedly Increased in Atherosclerotic Lesions Arterioscler Thromb Vasc Biol, November 1, 1999; 19(11): 2687 - 2695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Harada, Y. Toki, Y. Numaguchi, H. Osanai, T. Ito, K. Okumura, and T. Hayakawa Prostacyclin synthase gene transfer inhibits neointimal formation in rat balloon-injured arteries without bleeding complications Cardiovasc Res, August 1, 1999; 43(2): 481 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nishida, H. Ueno, N. Atsuchi, R. Kawano, Y. Asada, Y. Nakahara, Y.-i. Kamikubo, A. Takeshita, and H. Yasui Adenovirus-Mediated Local Expression of Human Tissue Factor Pathway Inhibitor Eliminates Shear Stress–Induced Recurrent Thrombosis in the Injured Carotid Artery of the Rabbit Circ. Res., June 25, 1999; 84(12): 1446 - 1452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Numaguchi, K. Naruse, M. Harada, H. Osanai, S. Mokuno, K. Murase, H. Matsui, Y. Toki, T. Ito, K. Okumura, et al. Prostacyclin Synthase Gene Transfer Accelerates Reendothelialization and Inhibits Neointimal Formation in Rat Carotid Arteries After Balloon Injury Arterioscler Thromb Vasc Biol, March 1, 1999; 19(3): 727 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. J. Kullo, R. D. Simari, and R. S. Schwartz Vascular Gene Transfer : From Bench to Bedside Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 196 - 207. [Full Text] [PDF]
|
|
|
|
|
|
I. Gussak, C. Antzelevitch, P. Bjerregaard, J. A. Towbin, and B. R. Chaitman The Brugada syndrome: clinical, electrophysiologic and genetic aspects J. Am. Coll. Cardiol., January 1, 1999; 33(1): 5 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Bouchie, H. Hansen, and E. P. Feener Natriuretic Factors and Nitric Oxide Suppress Plasminogen Activator Inhibitor-1 Expression in Vascular Smooth Muscle Cells : Role of cGMP in the Regulation of the Plasminogen System Arterioscler Thromb Vasc Biol, November 1, 1998; 18(11): 1771 - 1779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. Potter and T. Hunter Identification and Characterization of the Major Phosphorylation Sites of the B-type Natriuretic Peptide Receptor J. Biol. Chem., June 19, 1998; 273(25): 15533 - 15539. [Abstract] [Full Text] [PDF]
|
|