Atherosclerosis advanced

Free radicals might be involved in the incidences of various diseases such as arthritis, hemorrhagic shock, atherosclerosis, advancing age, ischemia and reperfusion injury of many organs, Alzheimer and Parkinson s disease, gastrointestinal dysfunctions, tumor promotion and carcinogenesis, AIDS, and other human health problems [85]. The oxidative proanthocyanidins as antioxidants could quench the free radicals and might help to enhance the action of other antioxidants such as vitamin C. 

Blanco-Vaca F, Escola-Gil JC, Martin-Campos JM, Julve J. Role of apoA-II in lipid metabolism and atherosclerosis advances in the study of an enigmatic protein. J Lipid Res 2001 42 1727-1739. 

Zemplenyi, T. The lipolytic and esterolytic activity of blood and tissues and problems of atherosclerosis. Advanc. Lipid Res. 2, 235—293 (1964). 

Our new appreciation of the role of inflammation in atherosclerosis shows the way for translation of these novel biological insights to clinical practice, for example by aiding the identification of individuals at risk of adverse cardiovascular events [5]. In this context, inflammatory biomarkers such as CRP merit rigorous consideration for inclusion in risk assessment strategies. In addition, these scientific advances provide a framework... 

Bea F, Blessing E, Bennett BJ, et al. Chronic inhibition of cyclooxygenase-2 does not alter plaque composition in a mouse model of advanced unstable atherosclerosis. Cardiovasc Res 2003 60(1) 198-204. 

Bea F, Blessing E, Shelley MI, Shultz JM, Rosenfeld ME. Simvastatin inhibits expression of tissue factor in advanced atherosclerotic lesions of apolipoprotein E deficient mice independently of lipid lowering potential role of simvastatin-mediated inhibition of Egr-1 expression and activation. Atherosclerosis 2003 167(2) 187-194. 

Tangirala, RK, Pratico, D, FitzGerald, GA, Chun, S, Tsukamoto, K, Maugeais, C, Usher, DC, Pure, E, and Rader, DJ, 2001. Reduction of isoprostanes and regression of advanced atherosclerosis by apolipoprotein E. J Biol Chem 276, 261-266. 

The expression of 15-LOX in atherosclerotic lesions is one of the major causes of LDL oxidative modification during atherosclerosis. To obtain the experimental evidence of a principal role of 15-LOX in atherosclerosis under in vivo conditions, Kuhn et al. [67] studied the structure of oxidized LDL isolated from the aorta of rabbits fed with a cholesterol-rich diet. It was found that specific LOX products were present in early atherosclerotic lesions. On the later stages of atherosclerosis the content of these products diminished while the amount of products originating from nonenzymatic lipid peroxidation increased. It was concluded that arachidonate 15-LOX is of pathophysiological importance at the early stages of atherosclerosis. Folcik et al. [68] demonstrated that 15-LOX contributed to the oxidation of LDL in human atherosclerotic plaques because they observed an increase in the stereospecificity of oxidation in oxidized products. Arachidonate 15-LOX is apparently more active in young human lesions and therefore, may be of pathophysiological importance for earlier atherosclerosis. In advanced human plaques nonenzymatic lipid peroxidation products prevailed [69],... 

A key concept inferred from the ideas discussed above is the difference between the development of conditions that favor the clinical eruption of any form of CVD (i.e., atherosclerosis) and the proper occurrence of the clinical event, since the inductors do not necessarily have to be the same. Furthermore, the possibility exists that a concrete factor may be protective at several stages of the silent form of the disease, but once it is sufficiently advanced, it may act as a trigger. This distinction is pivotal when considering the role of hormones, which have been shown to differentially regulate atherosclerosis and proper clinical events. 

Raloxifene and estrogen reduces progression of advanced atherosclerosis -a study in ovariectomized, cholesterol-fed rabbits. Atherosclerosis 154 97-102... 

The advanced lesions of atherosclerosis represent the culmination of a series of cellular and molecular events, involving replication of both smooth muscle cells and macrophages which have previously entered the artery wall. 

The interactions of these cells with T lymphocytes also in the lesion and the overlying endothelium can lead to a massive flbroproliferative response over which connective tissue from smooth muscle cells form a fibrous cap. This covers the advanced lesion or fibrous plaque of atherosclerosis, deeper portions of which consist of macrophages, T lymphocytes, smooth muscle cells, connective tissue, necrotic debris and varying amounts of lipids and lipoproteins. 

Cantero, A. V., Portero-Otin, M., Ayala, V., Auge, N., Sanson, M., Elbaz, M., Thiers, J. C., Pamplona, R., Salvayre, R., and Negre-Salvayre, A. (2007). Methylglyoxal induces advanced glycation end product (ages) formation and dysfunction of PDGF receptor-beta Implications for diabetic atherosclerosis. FASEB J. 21,3096-3106. 

Atherosclerosis The imaging of atherosclerosis with [ F]FDG PET was advanced and recent studies in rabbits showed that the tracer accumulated in macrophage-rich atherosclerotic plaques. It was assumed that the vascular macrophage activity can be quantified by p FlFDO PET [189]. Further studies in rabbits demonstrated that this imaging modality is useful for the clinical evaluation of therapeutic effects of drugs as well as for the development of new drugs that can reduce and inhibit inflammation of vulnerable plaques [190]. 

M. E. Rosenfeld, C.J. Schwartz, W.D. Wagner, R.W. Wissler, A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association, Circulation 92 (1995) 1355-1374. 

Cardiovascular heart diseases (CHD) are considered as the clinical expression of advanced atherosclerosis. One of the initial steps in atherogenesis is the oxidative modification of LDL and the uptake of the modified lipoprotein particles by macrophages, which in turn become lipid laden cholesterol-rich cells, so-called foam cells [159]. An accumulation of foam cells in the arterial wall is the first visible sign of atherosclerosis and is termed fatty streak, the precursor to the development of the occlusive plaque [160]. It is well known that oxidation of LDL can be initiated in vitro by incubating isolated LDL particles with cells (macrophages, lymphocytes, smooth muscle cells, or endothelial cells), metal ions (copper or iron), enzymes, oxygen radicals, or UV-light. However less is known about the mechanisms by which... 

The atherosclerotic lesions develop in a complex, chronic process. The first detectable lesion is the so-called fatty streak, an aggregation of lipid-laden macrophage foam cells. The next stage of development is the formation of plaques consisting of a core of lipid and necrotic cell debris covered by a layer of connective tissue and smooth muscle cells. These plaques hinder arterial blood flow and may precipitate clinical events by plaque rupture and thrombus formation. Platelets from the thrombi, activated macrophages, and smooth muscle cells release growth factors and cytokines resulting in an inflammatory-fibroproliferative response that leads to the advanced lesions of atherosclerosis. 

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