Skip to main content
Log in

Nitric oxide and pathogenic mechanisms involved in the development of vascular diseases

  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Nitric oxide (NO) is a pivotal signaling messenger in the cardiovascular system. NO participates in regulatory functions including control of hemostasis, fibrinolysis, platelet and leukocyte interactions with the arterial wall, regulation of vascular tone, proliferation of vascular smooth muscle cells, and homeostasis of blood pressure. Diminished NO bioavailability and abnormalities in NO-dependent signaling are among central factors of vascular disease, although it is unclear whether this is a cause of, or result of endothelial dysfunction or both pathogenic events. Disturbances in NO bioavailability have been linked to cause endothelial dysfunction, leading to increased susceptibility to atherosclerotic lesion progression, hypertension, hypercholesterolemia, diabetes mellitus, thrombosis and stroke.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Atkins, G. B. and Jain, M. K., Role of krüppel-like transcription actors in endothelial biology. Circ. Res., 100, 1686–16895 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Boon, R. A., Fledderus, J. O., Volger, O. L., van Wanrooij, E. J., Pardali, E., Weesie, F., Kuiper, J., Pannekoek, H., ten Dijke, P., and Horrevoets, A. J., KLF2 suppresses TGF-beta signaling in endothelium through induction of Smad7 and inhibition of AP-1. Arterioscler. Thromb. Vasc. Biol., 27, 532–539 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Bouhlel, M. A., Staels, B., and Chinetti-Gbaguidi, G., Peroxisome proliferator-activated receptors—from active regulators of macrophage biology to pharmacological targets in the treatment of cardiovascular disease. J. Intern. Med., 263, 28–42 (2008).

    PubMed  CAS  Google Scholar 

  • Cao, S., Yao, J., and Shah, V., The proline-rich domain of dynamin-2 is responsible for dynamin-dependent in vitro potentiation of endothelial nitric-oxide synthase activity via selective effects on reductase domain function. J. Biol. Chem., 278, 5894–5901 (2003).

    Article  PubMed  CAS  Google Scholar 

  • D’Armiento, F. P., Bianchi, A., De Nigris, F., Capuzzi, D. M., D’Armiento, M. R., Crimi, G., Abete, P., Palinski, W., Condorelli, M., and Napoli, C., Age-related effects on atherogenesis and scavenger enzymes of intracranial and extracranial arteries in men without classical risk factors for atherosclerosis. Stroke, 32, 2472–2479 (2001).

    Article  PubMed  Google Scholar 

  • de Nigris, F., Lerman, A., Ignarro, L. J., Ignarro-Williams, S., Sica, V., Baker, A. H., Lerman, L. O., Geng, Y. J., and Napoli, C., Oxidation-sensitive mechanisms, vascular apoptosis and atherosclerosis. Trends. Mol. Med., 9, 351–359 (2003).

    Article  PubMed  Google Scholar 

  • Dekker, R. J., Boon, R. A., Rondaij, M. G., Kragt, A., Volger, O. L., Elderkamp, Y. W., Meijers, J. C., Voorberg, J., Pannekoek, H., and Horrevoets, A. J., KLF2 provokes a gene expression pattern that establishes functional quiescent differentiation of the endothelium. Blood, 107, 4354–4363 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Dekker, R. J., van Thienen, J. V., Rohlena, J., de Jager, S. C., Elderkamp, Y. W., Seppen, J., de Vries, C. J., Biessen, E. A., van Berkel, T. J., Pannekoek, H., and Horrevoets, A. J., Endothelial KLF2 links local arterial shear stress levels to the expression of vascular tone-regulating genes. Am. J. Pathol., 167, 609–618 (2005).

    PubMed  CAS  Google Scholar 

  • Doughan, A. K., Harrison, D. G., and Dikalov, S. I., Molecular mechanisms of angiotensin II mediated mitochondrial dysfunction. linking mitochondrial oxidative damage and vascular endothelial dysfunction. Circ. Res., 102, 488–496 (2008).

    Article  PubMed  CAS  Google Scholar 

  • Fledderus, J. O., van Thienen, J. V., Boon, R. A., Dekker, R. J., Rohlena, J., Volger, O. L., Bijnens, A. P., Daemen, M. J., Kuiper, J., van Berkel, T. J., Pannekoek, H., and Horrevoets, A. J., Prolonged shear stress and KLF2 suppress constitutive pro-inflammatory transcription through inhibition of ATF2. Blood, 109, 4249–4257 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Cardena, G., Fan, R., Shah, V., Sorrentino, R., Cirino, G., Papapetropoulos, A., and Sessa, W. C., Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature, 392, 821–824 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Goodwin, B. L., Solomonson, L. P., and Eichler, D. C., Argininosuccinate synthase expression is required to maintain nitric oxide production and cell viability in aortic endothelial cells. J. Biol. Chem., 279, 18353–18360 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Goya, K., Sumitani, S., XU, X., Kitamura, T., Yamamoto, H., Kurebayashi, S., Saito, H., Kouhara, H., Kasayama, S., and Kawase, I., Peroxisome proliferator-activated receptor α agonists increase nitric oxide synthase expression in vascular endothelial cells. Arterioscler. Thromb. Vasc. Biol., 24, 658–663 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Hayashi, T., Juliet, P. A., Miyazaki, A., Ignarro, L. J., and Iguchi, A., High glucose downregulates the number of caveolae in monocytes through oxidative stress from NADPH oxidase: Implications for atherosclerosis. Biochim. Biophys. Acta., 1772, 364–372 (2007).

    PubMed  CAS  Google Scholar 

  • Ignarro, L. J., Cirino, G., Casini, A., and Napoli, C., Nitric oxide as a signaling molecule in the vascular system: An overview. J. Cardiovasc. Pharmacol., 34, 879–886 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Ignarro, L. J., Napoli, C., and Loscalzo, J., Nitric oxidedonating compounds and cardiovascular agents modulating the bioactivity of nitric oxide: An overview. Circ. Res., 90, 21–28 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Ignarro, L. J. and Napoli, C., Novel features on nitric oxide, endothelial nitric oxide synthase and atherosclerosis. Curr. Atheroscler. Rep., 6, 278–287 (2004).

    Article  Google Scholar 

  • Israelian-Konaraki, Z. and Reaven, P. D., Peroxisome proliferator-activated receptor-alpha and atherosclerosis: from basic mechanisms to clinical implications. Cardiol Rev., 13, 240–246 (2005).

    Article  PubMed  Google Scholar 

  • Lavi, S., Yang, E. H., Prasad, A., Mathew, V., Barsness, G. W., Rihal, C. S., Lerman, L. O., and Lerman, A., The interaction between coronary endothelial dysfunction, local oxidative stress, and endogenous nitric oxide in humans. Hypertension, 51, 127–133 (2008).

    Article  PubMed  CAS  Google Scholar 

  • Lim, E. J., Smart, E. J., Toborek, M., and Hennig, B., The role of caveolin-1 in PCB77-induced eNOS phosphorylation in human-derived endothelial cells. Am. J. Physiol. Heart. Circ. Physiol., 293, H3340–H3347 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Lin, Z., Kumar, A., Senbanerjee, S., Staniszewski, K., Parmar, K., Vaughan, D. E., Gimbrone, M. A. Jr, Balasubramanian, V., Garcia-Cardena, G., Jain, M. K., Kruppel-like factor 2 (KLF2) regulates endothelial thrombotic function. Circ. Res., 96, e48–e57 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Liu, V. W. T. and Huang, P. L., Cardiovascular roles of nitric oxide: A review of insights from nitric oxide synthase gene disrupted mice. Cardiovasc. Res., 77, 19–29 (2008).

    PubMed  CAS  Google Scholar 

  • Maniatis, N. A., Brovkovych, V., Allen, S. E., John, T. A., Shajahan, A. N., Tiruppathi, C., Vogel, S. M., Skidgel, R. A., Malik, A. B., and Minshall, R. D., Novel mechanism of endothelial nitric oxide synthase activation mediated by caveolae internalization in endothelial cells. Circ. Res., 99, 870–877 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Napoli, C., de Nigris, F., Williams-Ignarro, S., Pignalosa, O., Sica, V., and Ignarro, L. J., Nitric oxide and atherosclerosis: An update. Nitric Oxide, 15, 265–279 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Napoli, C. and Ignarro, L. J., Nitric oxide and atherosclerosis. Nitric Oxide, 5, 88–97 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Napoli, C. and Ignarro, L. J., Nitric oxide-releasing drugs. Annu. Rev. Pharmacol. Toxicol., 43, 97–123 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Napoli, C. and Ignarro, L. J., Polymorphisms in endothelial nitric oxide synthase and carotid artery atherosclerosis. J. Clin. Pathol., 60, 341–344 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Napoli, C., Lerman, L. O., De Nigris, F., Loscalzo, J., and Ignarro, L. J., Glyoxidized low-density lipoprotein down regulates endothelial nitric oxide synthase in human coronary cells. J. Am. Coll. Cardiol., 40, 1515–1522 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Napoli, C. and Lerman, L. O., Involvement of oxidation-sensitive mechanisms in the cardiovascular effects of hypercholesterolemia. Mayo Clin. Proc., 76, 619–631 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Napoli, C., Paterno, R., Faraci, F. M., Taguchi, H., Postiglione, A., and Heistad, D. D., Mildly oxidized low-density lipoprotein impairs responses of carotid but not basilar artery in rabbits. Stroke, 28, 2266–2272 (1997).

    PubMed  CAS  Google Scholar 

  • Napoli, C., Witztum, J. L., De Nigris, F., Palumbo, G., D’Armiento, F. P., and Palinski, W., Intracranial arteries of human fetuses are more resistant to hypercholesterolemia-induced fatty streak formation than extracranial arteries. Circulation, 99, 2003–2010 (1999).

    PubMed  CAS  Google Scholar 

  • Parmar, K. M., Larman, H. B., Dai, G., Zhang, Y., Wang, E. T., Moorthy, S. N., Kratz, J. R., Lin, Z., Jain, M. K., Gimbrone, M. A. Jr, and Garcia-Cardena, G., Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. J. Clin. Invest., 116, 49–58 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Parmar, K. M., Nambudiri, V., Dai, G., Larman, H. B., Gimbrone, M. A. Jr, and Garcia-Cardena, G., Statins exert endothelial atheroprotective effects via the KLF2 transcription factor. J. Biol. Chem., 280, 26714–26719 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Rabelink, T. J. and Luscher, T. F., Endothelial Nitric Oxide Synthase: Host defense enzyme of the endothelium? Arterioscler. Thromb. Vasc. Biol., 26, 267–271 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Schiffrin, E. L., Oxidative stress, nitric oxide synthase, and superoxide dismutase: A matter of imbalance underlies endothelial dysfunction in the human coronary circulation. Hypertension, 51, 31–32 (2008).

    Article  PubMed  CAS  Google Scholar 

  • Sen-Banerjee, S., Lin, Z., Atkins, G. B., Greif, D. M., Rao, R. M., Kumar, A., Feinberg, M. W., Chen, Z., Simon, D. I., Luscinskas, F. W., Michel, T. M., Gimbrone, M. A. Jr, Garcia-Cardena, G., and Jain, M. K., KLF2 is a novel transcriptional regulator of endothelial proinflammatory activation. J. Exp. Med., 199, 1305–1315 (2004).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Claudio Napoli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Napoli, C., Ignarro, L.J. Nitric oxide and pathogenic mechanisms involved in the development of vascular diseases. Arch. Pharm. Res. 32, 1103–1108 (2009). https://doi.org/10.1007/s12272-009-1801-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-009-1801-1

Key words

Navigation