**1. Introduction**

444 Lipoproteins – Role in Health and Diseases

Punjabis. PloS One 6(5).

805. Accessed 2011 May 24

Xue Xue Bao Yi Xue Ban. 42:24-28.

1409.

373.

[85] Gupta N, Singh S, Maturu N, Sharma YP, Gill KD (2011) Paraoxonase 1 Polymorphisms, Haplotypes and Activity in Predicting CAD Risk in North-West Indian

Available:http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017

[86] Suehiro T, Nakamura T, Inoue M, Shiinoki T, Ikeda Y, Kumon Y, Shindo M, Tanaka H, Hashimoto K (2000) A Polymorphism Upstream From the Human Paraoxonase (PON1)

[88] Mohamed Ali S, Chia SE (2008) Interethnic Variability of Plasma Paraoxonase (PON1) Activity Towards Organophosphates and PON1 Polymorphism Among Asian

[89] Zhang F, Liu HW, Fan P, Bai H, Song Q (2011) The -108 C/T Polymorphism in Paraoxonase 1 Gene in Chinese Patients With Polycystic Ovary Syndrome. Sichuan Da

[90] Sepahvand F, Rahimi-Moghaddam P, Shafiei M, Ghaffari SM, Rostam-Shirazi M, Mahmoudian M (2007) Frequency of Paraoxonase 192/55 Polymorphism in an Iranian

[91] McKeown-Eyssen C, Baines C, Cole DEC, Riley N, Tyndale RF, Marshall L, Jazmaji V (2004) Case-Control Study of Genotypes in Multiple Chemical Sensitivity: CYP2D6,

[92] Chen J, Kumar M, Chen W, Berkowitz G, wetmur JG (2003) Increased Influence of Genetic Variation on PON1 Activity in Neonates. Environ. Health Perspect. 111:1403–

[93] Santos NPC, Santos AKCR, Santos SEB (2005) Frequency of the Q192R and L55M Polymorphisms of the Human Serum Paraoxonase Gene (PON1) in Ten Amazonian

[94] Rojas-Garcia AE, Solis-Heredia MJ, Pina-Guzman B, Vega L, LopezCarrillo L, Quintanilla-Vega B (2005) Genetic Polymorphisms and Activity of PON1 in a Mexican

[95] Cataño HC, Cueva JL, Cardenas AM, Izaguirre V, Zavaleta AI, Carranca E, Hernández AF (2006) Distribution of Paraoxonase-1 Gene Polymorphisms and Enzyme Activity in

[96] Scacchi R, Corbo RM, Rickards O, De Stefano GF (2003) New Data on the World Distribution of Paraoxonase (PON1Gln192→Arg) Gene Frequencies. Hum. Biol. 75:365-

[97] El-Fasakhany FM, El-Segeaya O, Alahwal L, Abu Al-Nooman S (2007) Paraoxonase 1 Activity and Paraoxonase 192 Gene Polymorphism in Non Insulin Dependent Diabetes

Mellitus Patients Among Egyptian Population. Tanta. Med. Scien. J. 2:68-77.

Gene and its Asociation With PON1 Expression. Atherosclerosis. 150:295-298. [87] Hong SH, Song J, Min WK, Kim JQ (2001) Genetic Variations of the Paraoxonase Gene

in Patients With Coronary Artery Disease. Clin. Biochem. 34:475-481.

Populations-a Short Review. Ind. Health 46:309-317.

Population. J. Toxicol. Environ. Health 70:1125–1129.

Amerindian Tribes. Genet. Mol. Biol. 28:36-39.

Population. Toxicol. Appl. Pharmacol. 205:282–289.

a Peruvian Population. Environ. Molecul. Mutagen. 47:699-706.

NAT1, NAT2, PON1, PON2 and MTHFR. Int. J. Epidem. 33:1–8.

The oxidative hypothesis of atherosclerosis states that peroxide modification of LDL (or other lipoproteins) is important and probably required for the pathogenesis of arterial sclerotic disease; thus, there is an assumption that inhibition of LDL oxidation would increase or prevent atherosclerosis and its clinical consequences [1]. It is believed that the basis for the atherosclerotic plaque development is the foam cell formation from oxidized low-density lipoproteins (LDL) captured by monocytes and macrophages via scavenger-receptors.

Oxidation of LDL is also important for the healthy vessel functioning. High LDL concentrations can suppress the function of arteries in relation to release of nitric oxide from the endothelium, and many of such effects are mediated by the products of lipid oxidation [2]. Moreover, oxidized LDL inhibit the endothelium-dependent nitric oxide mediated relaxations in a rabbit isolated coronary arteries. Oxidized LDL induce apoptosis in the vascular cells, including macrophages, and this is prevented by nitric oxide [3].

One of the most important mechanisms of the inflammation proatherogenic effect is development of the systemic oxidative stress, and, as a consequence of proatherogenic abnormalities of the blood lipoprotein metabolism, there is appearance of antibodies to them, alterations of the main artery wall structure [4].

At the same time, on the one hand, a high atherogenicity of strongly oxidized LDL, especially tiny subfractions, has been confirmed; on the other hand, the oxidative stress is one of the causes of endothelial dysfunction.

© 2012 Zagaykoet al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Endothelium vascular wall cells are involved into the interaction with the pathogenic LDL [5]. While macrophages are being overloaded with esterified cholesterol, oxysterols and other biologically active substances, including powerful enzymes with a wide spectrum of action, a foam cell is formed from the macrophage. Yet so far to its apoptosis the foam cell secrets a wide complex of interleukins, enzymes, mediators. Many of them induce a local inflammatory process, destruction of the surrounding intercellular substance, damage of the fibrous structures and separate cells.

Many factors are considered as the most important factors for atherosclerosis development risk. Among such factors an important role belongs to the so-called proatherogenic states, including chronic stress and metabolic syndrome (MS) [6]. The proatherogenic character of stress is connected, first of all, with the activation of free radical oxidation and hyperlipidemia development. One of the principal statements of all contemporary conceptions of the atherosclerosis pathogenesis is thought to be the destruction of the cell membrane structure, which universal damage factor is peroxide oxidation of lipids (POL) [7].

It is well-known that free-radical processes play the leading role in atherosclerosis pathogenesis. So the antioxidants using in correction of proatherogenic states is fully explicable especially when we speak about natural antioxidants. Thus, the investigation of their biological effects under stress and metabolic syndrome is of grate interest and may be a perspective direction of research.

At the same time it is known that the enzymes associated with HDL, paraoxonase and PAFacetyl hydrolase can hydrolyse biologically active lipids of mm-LDL, destroy monocyte aggregates and decrease the endothelial activation of mm-LDL [8]. HDL also contain a high concentration of tocopherol due to which they can be free radical scavengers as well.

Antioxidants protect LDL from peroxide oxidation and consequently from intensive uptake of LDL by macrophages decreasing the foam cell formation, the endothelium damage and possibility for lipids to infiltrate the intima. This condition supports the actuality of searching medicines for treating atherosclerosis, in which inhibition of the POL process plays an important part in the mechanism of their action [9]. Tocopherol, carotene, probucol, a number of plant medicines containing flavonoids are proposed as antioxidants.

The overwhelming majority of antioxidant substances used in pharmacotherapy are xenobiotics and so substrates of CYP system actvating ROS formation. Moreover some of them, such as probucol, leade to HDL-C decreasing.

Therefore, the substances of natural, in particular, plant origins that possess a complex activity draw attention of researchers.

Phenolic compounds are widely present in the world of plants; they are the most widespread product of the plant metabolism. Participation of polyphenols in redox processes to produce stable quinone structures by their phenolic forms reveals an antiradical direction of their action which provides their direct antioxidant activity. At present it has been proven that polyphenols as antiradical agents not only hinder the initiation of free radical oxidation, but also interrupt the chain of lipoperoxidation [10]. A great variety of studies carried out both *in vitro* and *in vivo* supports the ability of polyphenols to inactivate ("to bind", "to scavenge") the radicals that initiate chains of oxidation. First of all, it relates to the primary ROS - **·** O2 and **·** OH [11].

There are some data that such natural polyphenols as catechins and procyanidins exposed to the human blood plasma produce certain complexes primarily with ApoA-1, i.e. with HDL.

One of the richest sources of polyphenols is *Vitis vinifera* and products of its processing, in particular wine.

Phenolic substances of grapes, including flavonoids and other polyphenols of grape, wine and grape seeds, are of a great interest due to their antioxidant properties and the ability to scavenge free radicals [12].

Studies *in vitro* have shown that grape, wine and grape seeds inhibit the oxidation of LDL. The activity of those substances as oxidation inhibitors in wine diluted 1,000 times markedly exceeded the analogous values for vitamins C and E [13]. It has been experimentally proven that red wine polyphenols slow down LDL oxidation processes and prevent platelet aggregation, thus preventing coronary heart diseases [14].

However, there is not a lot of research in this field yet. Arguments for anti-atherogenic properties of antioxidants are not enough. Results of convincing research are needed in order to decisively recommend antioxidants for treatment and prophylaxis of atherosclerosis.
