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Endothelial Cell Dysfunction—a Key Factor in Atherogenesis and Its Reversal (Laboratory and Clinical Study)

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Atherosclerosis, Hypertension and Diabetes

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 8))

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Abstract

In macrophage cell cultures and DNA studies, we recorded morphological changes and DNA damage caused by hydrogen peroxide exposure. In another experiment, interac-tion of altered macrophages and OX-LDL resulted in foam cells. In another experiment native LDL was converted to oxidised LDL by exposure to cigarette smoke extract. However pre-treatment with anti-oxidants-superoxide dismutase (SOD), nitric oxide (NO), glutathione peroxidase (GPx), vitamins A, E, C, â-carotene in all above experiments reversed partially/completely oxidative damage of macrophages, DNA, LDL and prevented foam fell formation. Clinical study included 100 documented cases of coronary artery disease (CAD), (50-angiographically proved, 50 acute myocardial infarction patients and 100 healthy controls (angiographically negative). We estimated oxidative stress (thiobarbituric acid reactive sub-stances and conjugated diene levels) and antioxidant levels (SOD, NO, GPx, vitamins A, E, C, â-carotene, selenium) in all. Oxidative stress was significantly increased and anti-oxidant levels were significantly low in CAD group. Low NO levels in CAD reflect endothelial cell dysfunction (ECD). Coronary artery lesions improved with treatment.

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References

  1. Kaiser L, Sparks HV. 1987. Endothelial cells: not just a cellophane wrapper. Arch Intern Medicine 147:569–573.

    Article  CAS  Google Scholar 

  2. Petty PG, Pearson JD. 1989. Endothelium the axis of vascular health and disease. Jr Royal Coll Physicians 23:92–101.

    CAS  Google Scholar 

  3. Celermajor DS. 1997. Endothelial dysfunction: Does it matter? Is it reversible?. Am Col of Cardiology 30:325–333.

    Article  Google Scholar 

  4. Kelly RA, Smith IW. 1996. Nitric oxides and nitrovasodilators-Similarities, differences and interactions and interactions. Amer Journ of Cardiol 2C–7C.

    Google Scholar 

  5. Dinerman JL, Mehta JL. 1990. Endothelial platelet and leukocyte interactions in ischaemic heart disease in sights into potential mechanism and their clinical relevance, Journ Am Coll Cardiology 16:207–222.

    Article  CAS  Google Scholar 

  6. Shah PK. 1997. New insights into the pathogenesis and prevention of acute coronary syndromes Am. Journ. Cardiol 79(12B):17–23.

    Article  CAS  Google Scholar 

  7. Masaki T. 1989. The discovery, the present state and the future prospects of endothelin. Journ Cardio vas. Pharmacology, 1989, 13, suppl 5: S1—S4.

    Article  CAS  Google Scholar 

  8. Awiram M, Dankner G, Brook JG. 1990. Platelet secretory products increases LDL oxidation, enhance its uptake by macrophages and reduces its fluidity. Arteriosclerosis 10:559–563.

    Article  Google Scholar 

  9. Shah PK. 1996. Pathophysiology of plaque rupture and concept of plaque stabilisation. Cardiol Clin 14:17–29.

    Article  PubMed  CAS  Google Scholar 

  10. Yagi K. 1984. Increased serum lipid peroxides initiate atherogeneses. Bioassays 1:58–60.

    Article  CAS  Google Scholar 

  11. Mehmetcik GT, Uysal M. 1997. Endogenous and Copper-induced lipid peroxidation and anti-oxidant activity of serum in hypercholesterolemic subject. Hormone Metabolism Research 29: 63–65.

    Article  CAS  Google Scholar 

  12. Mc Cord JM, Crapo JD, Fidovich I. 1997. Superoxided ismutase assays. A review of methodology. In: superoxide and superoxide dismutases, Ed. AM Michelson, JM McCord, I Fidovich, 11–17, London, UK Academic.

    Google Scholar 

  13. Green LC, Wagner DA, Glogoswski J, Skipper PL, Wishnok JS, Tannendaum SR. 1982. Analysis of nitrate, nitrate and (SN) nitrate in biological fluids. Analytical Biochem 126:131–138.

    Article  CAS  Google Scholar 

  14. Buczynski A, Wachowicz B, Kedziora-Kornatowaska K, Tkaczewski W, Kedziora J. 1993. Changes in antioxidant enzyme activities, aggregrability and malonyldialdehyde concentrations in blood, platelets from patients with CHD, Atherosclerosis 100(2):223–228.

    Article  PubMed  CAS  Google Scholar 

  15. Gey KF, Puska P. 1989. Plasma vitamin E and A inversely correlated to mortality from ischaemic heart disease in cross-cultural epidemiology, Ann New York Acad Sci 57:254–282.

    Google Scholar 

  16. Lantos J, Roth E, Czopf L, Nemes J, Gal I. 1997. Monitoring of plasma total antioxidant status in different diseases, Acta Chirurgica Hungarica 36(1–4): 188–189.

    PubMed  CAS  Google Scholar 

  17. de Bono DP, Yang WD. 1995. Exposure to low concentrations of H2O2 causes delayed endothelial cell death and inhibits proliferations of surviving cells. Atherosclerosis 114:235–245.

    Article  PubMed  Google Scholar 

  18. Whorton AR, Montgomery ME, Kent RS. 1985. Effects of hydrogen peroxide on prostaglandins production and cellular integrity in cultured porcine endothelial cells, Journ Clinical Investigations 76:295–296.

    Article  CAS  Google Scholar 

  19. Tharng SA, Abbot SE, Winward PG, Blake DR, Mills PG. 1996. Extent of oxidative modification of LDL, determines the degree of cytotoxicity to human coronary artery cells, Heart 75:11–16.

    Article  Google Scholar 

  20. Esterbauer H, Dicher-Rothencder M, Wagg G, Streiyel G, Jurgens G. 1990. Biochemical structural and functional properties of oxidised LDL, Chem Res Toxicol 3:77–92.

    Article  PubMed  CAS  Google Scholar 

  21. Prya WA, Stone K. 1993. Oxidants in cigarette smoke, Radicals hydrogen peroxide peroxynitrate and peroxynitrite. Ann New York Acad Sci 686:12–27.

    Article  Google Scholar 

  22. Wald NS, Howard PG, Smith, Kjeldsen K. 1973. Association between atherosclerosis diseases and carboxy-haemoglobin levels in tobacco smokers. British Med Journ 1:761–765.

    Article  CAS  Google Scholar 

  23. Frie B, Forte TM, Ames BM, Cross CE. 1991. Gas phase oxidants of cigarette smoke induce lipid perioxidant and changes in lipoprotein properties in human blood plasma Protective effects of ascor-bic acid, Biochem Journ 117:133–138.

    Google Scholar 

  24. Mello AC, Hoftmann ME, Menghini R. 1984. Cell Killing and DNA damage by hydrogen perox-ide are mediated by intracellular iron, Biochem Journ 218:273–275.

    Google Scholar 

  25. Schranf S, Hyslop PA, Jackson H, Cochrane LG. 1988. Oxidant included DNA damage of target cells, Journ Clin Invest 82:1040–1050.

    Article  Google Scholar 

  26. Cantoni O, Sestili P, Cattabeni F B, Bellomo G, Pou S, Cohen M, Cerutti P. 1989. Calcium chela-tor Quin 2 prevents hydrogen peroxide induced DNA breakage and cytotoxicity, Eur Journ Biochem 182:209–212.

    Article  CAS  Google Scholar 

  27. Singh RB, Niaz MA. 1993. CHD in Indians, Pakistanis and Bangladeshis; aetiology and possibilities for prevention (letter) British Heart Journ 69:572.

    Article  CAS  Google Scholar 

  28. Singhal S, Gupta P, Mathur B, Banda S, Dandia R, Gupta R. 1998. Educational status and dietary fat and antioxidant intake in urban subjects. JAPI 46/8:684–688.

    PubMed  CAS  Google Scholar 

  29. Nand N, Budhiraja N, Singh GP, Sharma M, Aggarwal HK. 1997. Lipid peroxidation and vitamin- E in IHD, JAPI 45/11:839–841.

    PubMed  CAS  Google Scholar 

  30. Subramanyam G. 1998. Role of trace elements and antioxidants in cardiovascular diseases. Cardiology Today II/1:59–64.

    Google Scholar 

  31. Chin HC, Jeng JR, Shiel SM. 1994. Increased oxidizability of plasma LDL from patients with CAD, Biochem Biophys, Acta 1225:200–208.

    Article  Google Scholar 

  32. Sanderson KJ, Vanrij AM, Wade CR, Sutherland HE 1995. Lipid peroxidation of circulating LDL with age, smoking and in peripheral vascular disease, Atherosclerosis 118:45–51.

    Article  PubMed  CAS  Google Scholar 

  33. Goto Y. 1982. Lipid peroxides as a cause of vascular disease. In: Lipid peroxides in biology and medicine. Edn Yogi K 295:303-NY Academic Press Inc.

    Google Scholar 

  34. Heinle H, Liebich H. 1980. The influence of diet-induced hypercholesterolemia with the degree of oxidation of glutathione in rabbit aorta. Atherosclerosis 37:637–640.

    Article  PubMed  CAS  Google Scholar 

  35. Sies H. 1993. Strategies on antioxidant defense. Eur, J Biochem 215:213–219.

    CAS  Google Scholar 

  36. Steinberg D, Parthasarathy T, Carew J. 1989. Beyond cholesterol-Modification of LDL that increases its atherogenicity. New England of Medicine 320(14):915–924.

    Article  CAS  Google Scholar 

  37. Goldstein S, Czapski G. 1984. Mannitol as an OH scavenger in aqueous solutions and in biological systems, Int. Journ. Radiation Biology 46:725–729.

    Article  CAS  Google Scholar 

  38. Vollset SE, Bjelke E. 1983. Does consumption of fruits and vegetables protect against stroke, Lancet 2:742 (letter).

    Google Scholar 

  39. Gey KF, Stahelin HB, Eichhdzer M. 1993. Poor plasma status of carotene and Vitamin C is associ-ated with higher mortality from IHD and stroke. Prospective Basel Study. Clinical Invest 7:3–6.

    Article  Google Scholar 

  40. Stampfer MJ, Hennekns CH, Mansan JF, Colditz GA, Rosner B, Willett WC. 1993. Vitamin E con-sumption and the risk of coronary disease in women. New England Journ of Med 328:1444–1449.

    Article  CAS  Google Scholar 

  41. Enstram JE, Kanim LE, Klein MA. 1992. Vitamin C intake and mortality among a sample of the United States population. Epidemiology 3:194–202.

    Article  Google Scholar 

  42. Gey KF. 1993. Vitamin E and other essential antioxidant regarding CHD: Risk assessment studies. In Vitamin E in health and disease, edn. L-Packer and J Fuchs, 589–633, New York, Dekkes.

    Google Scholar 

  43. Gey KF, Puska P, Jordan P, Meser UK. 1991. Inverse correlation between plasma Vitamin-E and mor-tality from IHD in cross epidemiology. Am Journ, Clin Nutr 53:326S–334S.

    Google Scholar 

  44. Morris Dl, Kritchevksy SB, Davis CE. 1994. Serum carotenoids and coronary heart disease, the lipid research clinics coronary primary prevention trial and follow-up stud., Jr. Am Med. Assoc 272:1439–1441.

    Article  CAS  Google Scholar 

  45. Burton KP. 1985. SOD enhances recovery following myocardial ischaemia. American Journal of Physiology 248:4637–4643.

    Google Scholar 

  46. Araujo FB, Barbosa DS, Hsin CY, Maranhao RC, Abadalla DS. 1995. Evaluation of oxidative stress in patients with hyperlipidemia. Atherosclerosis 117:61–71.

    Article  PubMed  CAS  Google Scholar 

  47. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. 1973. Selenium bio-chemical role as a component of glutathione peroxidase, Science 179:585–590.

    Article  Google Scholar 

  48. Salonen JT, Alfthan GH, Hunthuenen JK, Pikkarainen J, Puska P. 1982. Association between cardio-vascular death and myocardial infarction and serum selenium in a matched pair longitudinal study. Lancet 2:175–179.

    Article  PubMed  CAS  Google Scholar 

  49. Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willet WC. 1993. Vitamin E consumption and the risk of coronary heart disease in men. New England Journ of Med 328: 1450–1456.

    Article  CAS  Google Scholar 

  50. Singh RB, Nizam MA, Bishnoi I, Sharma JP, Gupta S, Rastogi SS, Singh R, Begum R, Chibo H, Shoumin Z 1994. Diet, antioxidant vitamins, oxidative stress and the risk of CAD, The Peerzada prospective study. Acta Cardiologica XLIX:453–467.

    Google Scholar 

  51. Singh RB, Rastogi S, Ghosh S, Nizam MA, Singh NK. 1993. The diet and moderate exercise trial (DAMET) results after 24 weeks. Acta Cardiologica 48:543–547.

    Google Scholar 

  52. The alpha tocopherol, Beta-carotene, cancer prevention study group (ATBC-group) 1994. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. New England Journ Of Medicine 330:1029–1035.

    Google Scholar 

  53. Frei B, England L, Ames BN. 1998. Ascorbate is an outstanding antioxidant in human blood plasma, Proc Natl Acad Sci USA 86:6377–6381.

    Article  Google Scholar 

  54. Golumbic C, Mattil HA. 1941. Antioxidants and the antioxidants of fats XIII The antioxygenic action of ascorbic acid in association with tocopherols hydroquinoes and related compounds, Journ Am Chem Soc 63:1279–1280.

    Article  CAS  Google Scholar 

  55. Riemersma RA, Wood DA, Macintyre CH, Elton RA, Gey KP, Oliver ME 1991. Risk of angina pectoris and plasma concentrations of vitamins A, C, E and carotene. Lancet 337:1–5.

    Article  CAS  Google Scholar 

  56. Prasad K, Kalra J. 1993. Oxygen free radicals and hypercholesterolemic atheroclerosis, effect of vitamin E, American Heart Journ 25:958–973.

    Article  Google Scholar 

  57. Verlangieri AJ, Bush MJ. 1992. Effects of d CC-tocopherol supplementation on experimentally induced primate atherosclerosis, Tourn Am Coll. Nutrition 11:131–138.

    CAS  Google Scholar 

  58. Gupta V, Chandra M, Johri AK, Mishra R, Kumar A, Gujrati V, Shanker K. 1994. Effect of oral vitamin E on oxy free radicals in AMI, Indian Heart Journal 46:222–224.

    Google Scholar 

  59. Daga MK, Madhuchhanda, Mishra TK, Mohan A. 1997. Lipid peroxide, beta carotene and alpha tocopherol in ischaemic stroke and effect of exogenous vitamin E supplementation on outcome, JAPI 45/11:843–846.

    PubMed  CAS  Google Scholar 

  60. Singh RB, Niaz M, Rastogi SS. 1996. Usefulness of antioxidant vitamins in suspected AMI (The Indian Experiment of Infarct survival-3) Am Journ of Cardiology 77:232–236.

    Article  CAS  Google Scholar 

  61. Cooke JP, Singer AH, Tsao P, Zera P, Rowan RA, Billinghem OF, Eichler HG. 1992. Antiathero-genic effects of L arginine in the hypercholesterolemic rabbit. Journ Clin Invest 90:1168–1172.

    Article  CAS  Google Scholar 

  62. Jilma B, Kastner J, Mensik C, Vondrovec B, Mildebrandt J, Krejcy K, Wagneri. 1996. Sex differ-ences in concentrations of exhaled NO and plasma nitrate, Life Science 58:469–476.

    Article  CAS  Google Scholar 

  63. Jacob RA. 1995. The integrated antioxidant system, Nutrition Research 15:755–756.

    Article  CAS  Google Scholar 

  64. Halliwell B, Gutteridge JMC. 1990. The antioxidant of human extracellular fluids, Arch Biochem Biophys 289:1–8.

    Article  Google Scholar 

  65. Gaziano JM, Mansen JE, Branch LG, Colditz GA, Willett WC, Buring JE. 1992. Dietary beta-carotene and decreased cardiovascular mortality in an elderly cohort, Journ, Am Coll Cardiology 19:377 (abstract).

    Google Scholar 

  66. Gage JE, Hess OM, Murakami T, Ritter M, Grimm J, Krayenbuchl HP. 1986. Vasoconstriction of stenotic coronary arteries during dynamic exercise in patients with classic angina pectoris. Reversibility by nitroglycerin. Circulation 73:865–876.

    Article  PubMed  CAS  Google Scholar 

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Sainani, G.S., Bhatia, M.S., Sainani, R. (2003). Endothelial Cell Dysfunction—a Key Factor in Atherogenesis and Its Reversal (Laboratory and Clinical Study). In: Pierce, G.N., Nagano, M., Zahradka, P., Dhalla, N.S. (eds) Atherosclerosis, Hypertension and Diabetes. Progress in Experimental Cardiology, vol 8. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9232-1_3

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  • DOI: https://doi.org/10.1007/978-1-4419-9232-1_3

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