LDL Oxidation and Vitamin E and Vitamin a Contents of LDL in Male Patients with Early-Onset Coronary Heart Disease and in Their 1st-Degree Male Relatives

Abstract

Objective: Coronary Heart Disease CHD , of which the primary cause is atherosclerosis, is among the leading causes of mortality in the developed countries. Although many etiological agents have been considered responsible for the development of the disease, oxidized LDL low-density lipoprotein is the major risk factor. Formation of atherosclerotic lesion begins with the macrophages’ turning oxidized LDL’s into foam cells. Although many factors such as high LDL concentration, hypertension and low antioxidants in the system impair vascular structure and initiate this process, the present study is based on the genetic susceptibility and the risk groups. The present study comprised the male patients with angiography-based diagnosis of early-onset coronary heart disease, as well as their sons or 1st-degree relatives, who are considered as high-risk group. It was aimed to compare these groups in terms of susceptibility of LDL to oxidation and to measure and compare vitamin E and A contents of LDL between these groups. Homocysteine concentration, which is considered as an independent risk factor for CHD, was also compared between the groups. Materials and Methods: Susceptibility of LDL to oxidation was determined based on the formation of conjugated dienes observing for 200 minutes after being incubated with cupper cu2+ ions. Vitamin E and A contents of LDL were measured by HPLC High-performance Liquid Chromatography , which is considered as the reference method. Male patients with early-onset coronary heart disease with >50% stenosis in at least two vessels on coronary angiography and their 1st-degree relatives were compared in terms of above-mentioned three parameters. In addition, FPIA Fluorescence Polarization Immuno-Assays was used to measure homocysteine concentration. Results: Three study groups were created: Group 1 consisted of 20 patients aged 40-55 years, who had >50% stenosis in 2 and/or more vessels detected on coronary angiography; Group 2 consisted of 18 subjects aged 18-20 years, who are the 1st-degree relatives sons or brothers of Group 1; Group 3 control group consisted of healthy males aged 18-35 years. Susceptibility of LDL to oxidation showed significant difference between Group 2 and Group 3. No statistically significant difference was determined between the groups in terms of LDL content of Vitamin A and E. Homocysteine concentration was significantly higher in Group 1 and Group 2. Conclusions: Early-onset CHD can be prevented or delayed by means of relevant screening and treatment of high-risk groups in the population.

Keywords

• LDL oxidation, early-onset coronary heart disease, vitamin E and A

References

1. 1. Zengin H. Ateroskleroz Patogenezi. J Exp Clin Med 2012;29:101–106. [CrossRef]
2. 2. Ahotopa M, Ruutu M, Mantyla E. Simple methods of quantifying oxidation products and antioxidant potential of low density lipoproteins. Clin Biochem 1996;29:139–144. [CrossRef]
3. 3. Kurnaz Ö, Yılmaz-Aydoğan H. Okside LDL reseptörü -1(lLOX1) ve kardiyovasküler hastalıklarla ilişkisi. Tıp Araştırmaları Derg 2014;12:145–152. [CrossRef]
4. 4. Wiesbauer F, Blessberger H, Azar D, et al. Familial-combined hyperlipidaemia in very young myocardial infarction survivors (
5. 5. Puhl H, Waeg G, Esterbauer H. Methods to determine oxidation of low-density lipoproteins. Methods Enzymol 1994;223:425–441. [CrossRef]
6. 6. Lowry OH, Rosenberg NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951;193:265–275. https:// www.jbc.org/content/193/1/265.long
7. 7. Bostom AG, Selhub J. Homocysteine and Arteriosclerosis. Circulation 1999;99:2361–2363. [CrossRef]
8. 8. Chia-Lun Chao, Tsung-Li Kuo, and Yuan-Teh Lee. Effects of Methionine-Induced Hyperhomocysteinemia on EndotheliumDependent Vasodilation and Oxidative Status in Healthy Adults. Circulation. 2000;101:485–490. [CrossRef]

9. 9. Hage D. Chromatography. In: Schoeff LE, Williams RH, editors. Principles of Laboratory Instruments. St. Luis: Mosby; 1993. p.182– 202.
10. 10. Kontush A, Beisigel U. Measurement of oxidizability of blood plasma. Methods Enzymol 1999;299:35–49. [CrossRef]
11. 11. Steinberg D. Oxidative Modification of LDL and atherogenesis (Lewis A. Conner Memorial Lecture). Circulation 1997;95:1062–1071. [CrossRef]
12. 12. Dandliker WB, De Saussure VA. Fluorescence polarization in immunochemistry. Immunochemistry 1970;7:799–828. [CrossRef]
13. 13. Fiore MD, Mitchell JE, Doan T, et al. The Abbot IMx Automated Benchtop Immunochemistry Analyzer System. Clin Chem 1988;34:1726–1732. [CrossRef]
14. 14. Witting PK, Mohr D, Stocker R. Assesment of prooxidant activity of vitamin E in human low-density lipoprotein and plasma. Methods Enziymol 1999;299:362–375. [CrossRef]
15. 15. Upston JM, Terentis AC, Stocker R. Tocopherol-mediated peroxidation of lipoproteins: implications for vitamin E as potential antiatherogenic supplement. FASEB J 1999;13:977–994. [CrossRef]
16. 16. Dieber-Rotheneder M, Puhl H, Waeg G, Striegl G, Esterbauer H. Effect of oral supplementation with D-alfa-tocopherol on the vitamin E content of human low density lipoproteins and resistance to oxidation. J Lipid Res 1991;32:1325–1332. https://www.jlr.org/ content/32/8/1325.long
17. 17. Karmansky I, Shnaider H, Palant A, Gruener N. Plasma lipid oxidation and susceptibility of low density lipoproteins to oxidation in male patients with stable coronary artery disease. Clin Biochem 1996;29:573–579. [CrossRef]
18. 18. Maron DJ, Ridker PM, Pearson TA. Risk factors and prevention of coronary heart disease. In: Alexander TW, Schlant RC, Fuster V, editors. Hurst’s the Heart, 9th ed. New York: Mc Graw Hill Health Profession Division; 1998. p.175–191.
19. 19. Berliner JA, Navab M, Fogelman AM, et al. Atherosklerosis: basic mechanisms oxidation, inflammation, and genetics. Circulation 1995;91:2488–2496. [CrossRef]