Atherosclerosis radical damage

Free radical damage is considered to be a causative factor in the development of cancer and inflammatory and chronic diseases. Therefore, free radical scavenging molecules (antioxidants) may play a beneficial role in these conditions. With repect to CVD, the oxidation of low-density lipoprotein (LDL) is believed to be a critical process in the development of atherosclerosis (Berliner et al., 1995 Navab et al., 1995). The presence of oxidized LDL in the intima of an artery leads to the production of macrophage-derived foam cells, the main cell type present in fatty streaks that are believed to be the earliest lesion of atherosclerosis (Fuster, 1994). Therefore, the use of antioxidants as dietary supplements to protect against LDL oxidation may reduce both the development and progression of atherosclerosis (Gey, 1995). 

Antioxidants derived from foods help to protect against free radical damage. Carotenoids are a very important class of antioxidants, as are vitamins A, C, and E. Carotenoids, including alpha carotene, beta carotene, lycopene, lutein, and zexanthin, have been demonstrated to protect against skin cancer, prostate cancer, and atherosclerosis, among others. Higher blood antioxidant levels have been correlated with lower blood levels of C-reactive protein (CRP), and thus lower inflammation of the blood vessels (and less atherosclerotic plaque). 

Lynn et al. [71] demonstrated the damaging effect of arsenite on DNA. It has been shown that arsenite at low concentrations increased DNA oxidative damage in vascular smooth muscle cells (VSMCs) that can be a cause of arsenite-induced atherosclerosis. Bruskov et al. [72] found that heat induced the formation of 8-oxoguanine in DNA solution at pH 6.8, which was supposedly mediated by oxygen radicals. 

Chelators of transition metals, mainly iron and copper, are usually considered as antioxidants because of their ability to inhibit free radical-mediated damaging processes. Actually, the so-called chelating therapy has been in the use probably even earlier than antioxidant therapy because it is an obvious pathway to treat the development of pathologies depending on metal overload (such as calcium overload in atherosclerosis or iron overload in thalassemia) with compounds capable of removing metals from an organism. Understanding of chelators as antioxidants came later when much attention was drawn to the possibility of in vivo hydroxyl radical formation via the Fenton reaction ... 

R. Olinski et al., Oxidative DNA damage Assessment of the role in carcinogenesis, atherosclerosis, and acquired immunodeficiency syndrome. Free Radic. Biol. Med. 33, 192-200 (2002)... 

Oxidation of cellular components by reactive oxygen species (ROS) and free radicals is involved in a variety of serious acute and chronic diseases inflammation [56], ischemia-reperfusion damage [57,58], limg disease [59], kidney damage [60], atherosclerosis, diabetes, allergies, cancer and aging [61]. 

Atherosclerosis, cancer and degenerative brain diseases may result from specific processes in an organ or a cell system and at the same time may be the result of the universal aging process. Damage to DNA by radicals may be a significant contributor to the age-dependent development of cancer (Halliwell, 1994). Diseases associated with oxidative stress, free radicals and metabolites generating free radicals in the body are listed in Table 3.7 (Stahelin, 1999). It is not yet clear, however, whether the oxidative stress is the primary cause of the diseases or whether formation of radicals is a secondary effect of tissue damage caused by the disease. 

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