(Circulation. 1997;95:1101-1103.)
© 1997 American Heart Association, Inc.
Articles |
What Are the Molecular Mechanisms for the Antiproliferative Effects of Nitric Oxide and cGMP in Vascular Smooth Muscle?
Correspondence to Ferid Murad, MD, PhD, 1421 Lake Rd, Lake Forest, IL 60045.
Key Words: Editorials • molecular biology • muscle, smooth
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Introduction |
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Although the smooth muscle antiproliferative effects of nitric oxide and cGMP in vascular preparations have been known for several years, the precise molecular mechanisms for these effects remain unknown. Presumably these effects participate in several vascular processes, including atherogenesis, reperfusion injury, angiogenesis, inflammation, tumor growth, wound healing, and tissue grafts. A molecular understanding of these effects would no doubt provide additional therapeutic interventions for these important disorders and processes. Although the information and publications in the field of nitric oxide and cGMP have grown logarithmically in the past two decades, many important questions remain to be answered and resolved. More than 4500 publications addressing these messengers were expected in 1996, probably more than for any other research topic. Nevertheless, many important experiments remain to be done. Readers are referred to several recent reviews summarizing the effects of nitric oxide and cGMP (References 1-3). Yu and colleagues4 address the vascular smooth muscle antiproliferative effects of these messengers in this issue of Circulation.
The authors find that SNP, a nitrovasodilator and nitric oxide donor or prodrug, and A-02131-1, a selective inhibitor of cGMP phosphodiesterase, decrease the proliferation of primary cultures of rat vascular smooth muscle cells that have been stimulated with one of several growth factors, such as epidermal growth factor, platelet-derived growth factor, phorbol myristate, or okadaic acid. The authors find that the effects are also mimicked by a cGMP analogue, 8-Br-cGMP, which can activate cGMP-dependent protein kinase (PKG) but is more resistant to hydrolysis by phosphodiesterase. The antiproliferative effects
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 T. Morishita, M. Tsutsui, H. Shimokawa, K. Sabanai, H. Tasaki, O. Suda, S. Nakata, A. Tanimoto, K.-Y. Wang, Y. Ueta, et al. Nephrogenic diabetes insipidus in mice lacking all nitric oxide synthase isoforms PNAS, July 26, 2005; 102(30): 10616 - 10621. [Abstract] [Full Text] [PDF]
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 N. C. Browner, N. B. Dey, K. D. Bloch, and T. M. Lincoln Regulation of cGMP-dependent Protein Kinase Expression by Soluble Guanylyl Cyclase in Vascular Smooth Muscle Cells J. Biol. Chem., November 5, 2004; 279(45): 46631 - 46636. [Abstract] [Full Text] [PDF]
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 T. L. Cornwell, E. K. Ceaser, J. Li, K. L. Marrs, V. M. Darley-Usmar, and R. P. Patel S-nitrosothiols inhibit uterine smooth muscle cell proliferation independent of metabolism to NO and cGMP formation Am J Physiol Cell Physiol, June 1, 2003; 284(6): C1516 - C1524. [Abstract] [Full Text] [PDF]
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 O. Gorchakova, W. Koch, N. von Beckerath, J. Mehilli, A. Schomig, and A. Kastrati Association of a genetic variant of endothelial nitric oxide synthase with the 1 year clinical outcome after coronary stent placement Eur. Heart J., May 1, 2003; 24(9): 820 - 827. [Abstract] [Full Text] [PDF]
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X. Feng, Z. Guo, M. Nourbakhsh, H. Hauser, R. Ganster, L. Shao, and D. A. Geller Identification of a negative response element in the human inducible nitric-oxide synthase (hiNOS) promoter: The role of NF-kappa B-repressing factor (NRF) in basal repression of the hiNOS gene PNAS, October 29, 2002; 99(22): 14212 - 14217. [Abstract] [Full Text] [PDF]
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 F. Yang, A. von Knethen, and B. Brüne Modulation of nitric oxide-evoked apoptosis by the p53-downstream target p21WAF1/CIP1 J. Leukoc. Biol., December 1, 2000; 68(6): 916 - 922. [Abstract] [Full Text]
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 M. Sata, M. Kakoki, D. Nagata, H. Nishimatsu, E. Suzuki, T. Aoyagi, S. Sugiura, H. Kojima, T. Nagano, K. Kangawa, et al. Adrenomedullin and Nitric Oxide Inhibit Human Endothelial Cell Apoptosis via a Cyclic GMP-Independent Mechanism Hypertension, July 1, 2000; 36(1): 83 - 88. [Abstract] [Full Text] [PDF]
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 L. Chen, G. Daum, J. W. Fischer, S. Hawkins, M.-L. Bochaton-Piallat, G. Gabbiani, and A. W. Clowes Loss of Expression of the {beta} Subunit of Soluble Guanylyl Cyclase Prevents Nitric Oxide-Mediated Inhibition of DNA Synthesis in Smooth Muscle Cells of Old Rats Circ. Res., March 17, 2000; 86(5): 520 - 525. [Abstract] [Full Text] [PDF]
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 M. Suhasini, H. Li, S. M. Lohmann, G. R. Boss, and R. B. Pilz Cyclic-GMP-Dependent Protein Kinase Inhibits the Ras/Mitogen-Activated Protein Kinase Pathway Mol. Cell. Biol., December 1, 1998; 18(12): 6983 - 6994. [Abstract] [Full Text] [PDF]
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