Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Mar 3;2020:1015908.
doi: 10.1155/2020/1015908. eCollection 2020.

Intraplatelet L-Arginine-Nitric Oxide Metabolic Pathway: From Discovery to Clinical Implications in Prevention and Treatment of Cardiovascular Disorders

Affiliations
Free PMC article
Review

Intraplatelet L-Arginine-Nitric Oxide Metabolic Pathway: From Discovery to Clinical Implications in Prevention and Treatment of Cardiovascular Disorders

Jakub Gawrys et al. Oxid Med Cell Longev. .
Free PMC article

Abstract

Despite the development of new drugs and other therapeutic strategies, cardiovascular disease (CVD) remains still the major cause of morbidity and mortality in the world population. A lot of research, performed mostly in the last three decades, revealed an important correlation between "classical" demographic and biochemical risk factors for CVD, (i.e., hypercholesterolemia, hyperhomocysteinemia, smoking, renal failure, aging, diabetes, and hypertension) with endothelial dysfunction associated directly with the nitric oxide deficiency. The discovery of nitric oxide and its recognition as an endothelial-derived relaxing factor was a breakthrough in understanding the pathophysiology and development of cardiovascular system disorders. The nitric oxide synthesis pathway and its regulation and association with cardiovascular risk factors were a common subject for research during the last decades. As nitric oxide synthase, especially its endothelial isoform, which plays a crucial role in the regulation of NO bioavailability, inhibiting its function results in the increase in the cardiovascular risk pattern. Among agents altering the production of nitric oxide, asymmetric dimethylarginine-the competitive inhibitor of NOS-appears to be the most important. In this review paper, we summarize the role of L-arginine-nitric oxide pathway in cardiovascular disorders with the focus on intraplatelet metabolism.

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Synthesis of ADMA from methylated proteins. SAM: S-adenosylmethionine; SAH: S-adenosylhomocysteine; PMRT-1: protein methyltransferase-1; PMRT-2: protein methyltransferase-2; SDMA: symmetric dimethylarginine; L-NMMA: monomethylated arginine; ADMA: asymmetric dimethylarginine; NOS: nitric oxide synthase; NO: nitric oxide. Based on [–32].
Figure 2
Figure 2
Potential homeostatic mechanism of autoregulation of nitric oxide production. NO: nitric oxide; NOS: nitric oxide synthase; ADMA: asymmetric dimethylarginine; DDAH: dimethylarginine dimethylaminohydrolase; ∗: reactions involving inducible nitric oxide synthase. Based on [38, 39].
Figure 3
Figure 3
The effect of hyperglycaemia on the L-arginine-nitric oxide pathway. ROS: reactive oxygen species; DDAH: dimethylarginine dimethylaminohydrolase; ADMA: asymmetric dimethylarginine; NOS: nitric oxide synthase; NO: nitric oxide. Authors' modification based on [–69].
Figure 4
Figure 4
The known functions of platelet-derived nitric oxide. Authors' modification on the basis of [83].

Similar articles

See all similar articles

References

    1. Furchgott R., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288(5789):373–376. doi: 10.1038/288373a0. - DOI - PubMed
    1. Furchgott R. F. Endothelium-derived relaxing factor: discovery, early studies, and identification as nitric oxide. Bioscience Reports. 1999;19(4):235–251. doi: 10.1023/a:1020537506008. - DOI - PubMed
    1. Moncada S., Palmer R. M. J., Higgs E. A. Biosynthesis of nitric oxide from l-arginine: A pathway for the regulation of cell function and communication. Biochemical Pharmacology. 1989;38(11):1709–1715. doi: 10.1016/0006-2952(89)90403-6. - DOI - PubMed
    1. Cellek S., Moncada S. Nitrergic modulation of cholinergic responses in the opossum lower oesophageal sphincter. British Journal of Pharmacology. 1997;122(6):1043–1046. doi: 10.1038/sj.bjp.0701497. - DOI - PMC - PubMed
    1. Roth G. A., Johnson C., Abajobir A., et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. Journal of the American College of Cardiology. 2017;70(1):1–25. doi: 10.1016/j.jacc.2017.04.052. - DOI - PMC - PubMed

LinkOut - more resources

Feedback