EC Pharmacology And Toxicology

This short review concerns the role of reactive oxygen species in cardiovascular diseases and the strategical ways of prevention. ROS have been implicated in the development of atherosclerosis and other CVDs due to their critical contribution to the oxidative stress, inflammation process, and impairment of blood vessels. Much attention is given to the enzyme NAD(P)H oxidase as an important source of ROS, especially in vascular cells. This enzyme also contributes to the formation of oxidative stress, especially in states such as hyperglycemia, a common condition in diabetes leading to vascular complications and heart disease. Oxidative stress may also be caused by hyperhomocysteinemia, which elevates stroke risk factors. The vitamins C, E, and β-carotene are suggested to be used as antioxidants against oxidative stress. These antioxidants strengthen the body’s defense systems and reduce the risk of atherosclerosis. Another mineral playing an important role in heart health is magnesium; its poor levels may lead to many cardiovascular diseases. Magnesium regulates blood pressure and heart function. Magnesium status is highly related to heart health, which needs a diet of high consumption from leafy greens, nuts, and seeds. The review also includes, among others, the biomarkers of oxidative stress in CVD: isoprostanes, malondialdehyde, and oxidized low-density lipoprotein. These markers are employed in assessing oxidative damage and predicting the development of a disease. Their correct quantification is important to understand the influence of oxidative stress on cardiovascular health.

 Keywords: Oxidative Stress; Atherosclerosis; Magnesium; Antioxidants; Biomarkers

1. Ounpuu S., et al. “The impending global epidemic of cardiovascular diseases”. European Heart Journal 21.11 (2000): 880-883.
2. Halliwell B and Gutteridge JMC. “Free radicals in biology and medicine”. 2nd edition. Oxford, UK, Clarendon Press (1989).
3. Tardif JC. “Studies on cardiovascular disorders”. Cardiology Grand Rounds 7 (2003): 1-6.
4. Lakshmi SVV., et al. “Estimation of antioxidant levels in saliva and serum of chronic periodontitis patients with and without ischemic heart disease”. Indian Journal of Biochemistry and Biophysics 46 (2009): 421-440.
5. Hamilton CAH., et al. “Strategies to reduce oxidative stress in cardiovascular disease”. Clinical Science 106.3 (2004): 219-234.
6. Madamanchi NR., et al. “Oxidative stress and vascular disease”. Arteriosclerosis, Thrombosis, and Vascular Biology 25.1 (2005): 29-38.
7. Gao L and Mann GE. “Vascular NAD(P)H oxidase activation in diabetes: a double-edged sword in redox signalling”. Cardiovascular Research 82.1 (2009): 9-20.
8. Mendes RH., et al. “Moderate hyperhomocysteinemia provokes dysfunction of cardiovascular autonomic system and liver oxidative stress in rats”. Autonomic Neuroscience 180 (2014): 43-47.
9. Wikipedia. NADPH oxidase.
10. Steinberg D and Witztum JL. “Lipoproteins and atherogenesis. Current concepts”. Journal of the American Medical Association 264.23 (1990): 3047-3052.
11. Esterbauer H., et al. “Vitamin E in health and disease”. Packer L, Fuchs ed. New-York, Marcel Dekker Inc, (1993): 647.
12. Porkkala-Sarataho EK., et al. “A randomized, single-blind, placebo-controlled trial of the effects of 200 mg alpha-tocopherol on the oxidation resistance of atherogenic lipoproteins”. American Journal of Clinical Nutrition 68.5 (1998): 1034-1041.
13. Jialal I., et al. “β-carotene inhibits the oxidative modification of low-density lipoprotein”. Biochimica et Biophysica Acta 1086.1 (1991): 134-138.
14. Allard JP., et al. “Effects of beta-carotene supplementation on lipid peroxidation in humans”. American Journal of Clinical Nutrition 59.4 (1994): 884-890.
15. Ringer TV., et al. “Beta-carotene’s effects on serum lipoproteins and immunologic indices in humans”. American Journal of Clinical Nutrition 53.3 (1991): 688-694.
16. Jialal I and Grundy SM. “Influence of antioxidant vitamins on LDL oxidation”. Annals of the New York Academy of Sciences 669 (1992): 237-247.
17. Harrison and Tinsley R. “Principles of Internal Medicine”. 13th edition, McGraw-Hill (1994): 1106-1115 and 2434-2435.
18. Ascherio Alberto., et al. “A prospective study of nutritional factors and hypertension among U.S. men”. Circulation 86.5 (1992): 1475-1484.
19. Aliments les plus riches en magnésium: le classement.
20. Eisenberg Mark J. “Magnesium deficiency and sudden death”. American Heart Journal 124.2 (1992): 544-549.
21. Shechter Michael., et al. “The rationale of magnesium supplementation in acute myocardial infarction: a review of the literature”. Archives of Internal Medicine 152.11 (1992): 2189-2196.
22. “Supplemental dietary potassium reduced the need for antihypertensive drug therapy”. Nutrition Reviews 50.5 (1992): 144-145.
23. Witteman Jacqueline CM., et al. “Reduction of blood pressure with oral magnesium supplementation in women with mild to moderate hypertension”. American Journal of Clinical Nutrition 60.1 (1994): 129-135.
24. Iseri Lloyd T., et al. “Magnesium therapy of cardiac arrhythmias in critical-care medicine”. Magnesium 8.5-6 (1989): 299-306.
25. Carolyn Dean. “The Magnesium Miracle (Revised and Updated Edition)” (2006).
26. JD Morrow. “Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans”. Arteriosclerosis, Thrombosis, and Vascular Biology 25.2 (2005): 279-286.
27. ES Musiek., et al. “Recent advances in the biochemistry and clinical relevance of the isoprostane pathway”. Lipids 40.10 (2005): 987-994.
28. KA Smith., et al. “A comparison of methods for the measurement of 8-isoPGF(2alpha): a marker of oxidative stress”. Annals of Clinical Biochemistry 48.2 (2011): 147-154.
29. T Wu., et al. “Stability of measurements of biomarkers of oxidative stress in blood over 36 hours”. Cancer Epidemiology, Biomarkers and Prevention 13.8 (2004): 1399-1402.
30. EA Meagher and GA FitzGerald. “Indices of lipid peroxidation in vivo: strengths and limitations”. Free Radical Biology and Medicine 28.12 (2000): 1745-1750.
31. RJ Bevan., et al. “Validation of a novel ELISA for measurement of MDA-LDL in human plasma”. Free Radical Biology and Medicine 35.5 (2003): 517-527.
32. MF Walter., et al. “Serum levels of thiobarbituric acid reactive substances predict cardiovascular events in patients with stable coronary artery disease: a longitudinal analysis of the PREVENT study”. Journal of the American College of Cardiology 44.10 (2004): 1996-2002.
33. JT Salonen., et al. “Lipoprotein oxidation and progression of carotid atherosclerosis”. Circulation 95.4 (1997): 840-845.
34. G Peluffo and R Radi. “Biochemistry of protein tyrosine nitration in cardiovascular pathology”. Cardiovascular Research 75.2 (2007): 291-302.
35. MH Shishehbor., et al. “Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy”. Journal of the American Medical Association 289.13 (2003): 1675-1680.
36. GA Figtree, et al. “Oxidative regulation of the Na(+)-K(+) pump in the cardiovascular system”. Free Radical Biology and Medicine 53.12 (2012): 2263-2268.
37. T Adachi., et al. “S-Glutathiolation by peroxynitrite activates SERCA during arterial relaxation by nitric oxide”. Nature Medicine 10.11 (2004): 1200-1207.
38. R Zhang., et al. “Association between myeloperoxidase levels and risk of coronary artery disease”. Journal of the American Medical Association 286.17 (2001): 2136-2142.
39. P Holvoet., et al. “Oxidized LDL and malondialdehyde-modified LDL in patients with acute coronary syndromes and stable coronary artery disease”. Circulation 98.15 (1998): 1487-1494.
40. S Ehara., et al. “Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes”. Circulation 103.15 (2001): 1955-1960.
41. S Singh., et al. “Nrf2-ARE stress response mechanism: a control point in oxidative stress-mediated dysfunctions and chronic inflammatory diseases”. Free Radical Research 44.11 (2010): 1267-1288.
42. J St-Pierre., et al. “Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators”. Cell 127.2 (2006): 397-408.
43. S Blankenberg, et al. “Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease”. New England Journal of Medicine 349.17 (2003): 1605-1613.