Atherosclerotic tissues

The same products were formed in the reaction of LDL with molecular chlorine but not with HOC1. These authors suggested that the formation of molecular chlorine might occur in vivo because a pH value could be less than 4 during macrophage phagocytosis. In addition, atherosclerotic tissue may also be relatively acidic due to impaired oxygen diffusion and hypoxia. 

Takeshita J, Byun J, Nhan TQ, Pritchard DK, Pennathur S, Schwartz SM, Chait A, Heinecke JW (2006) Myeloperoxidase Generates 5-Chlorouracil in Human Atherosclerotic Tissue. J Biol Chem 281 3096... 

Mattsson-Hulten, L., Lindmark, H., Diczfalusy, U., Bjorkhem, I., Ottosson, M., Liu, Y., Bondgers, G., Wilklund, O. 1996. Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human monocyte-derived macrophages. J. Clin. Invest. 97, 461-468. 

Diffuse reflection NIR spectroscopy has proven to be a useful technique for identifying chemical content of atherosclerotic tissues [35]. Our laboratory has described the use of NIR spectroscopy to categorize human aortic atherosclerotic plaques and to quantify cholesterol HDL, and LDL in arterial wall samples [33,34]. 

Their results indicated that non-atherosclerotic tissue, non-calcified atherosclerotic plaque and calcified atherosclerotic plaque all give different Raman spectra, and hence this technique can differentiate these three states of a vessel wall. Microscopic Raman spectra were obtained to study the chief constituents of the vessels under examination elastic laminae, collagen fibres, smooth muscle cells, fat cells, foam cells, necrotic cores, cholesterol crystals, p-carotene containing crystals, and calcium mineralisations. The results indicate different levels of each depending on which arterial sample was being observed. For example, calcified atherosclerotic plaques contained a lot more foci of calcium... 

Atherosclerotic tissue Is reported to have a higher cholesterol esterification rate than normal arterial tissue, > as well as a greater permeability to cholesterol esters bound to lipoprotein. ... 

The concentration of t-PA in human blood is 2—5 ng/mL, ie, 2—5 ppb. Plasminogen activation is accelerated in the presence of a clot, but the rate is slow. The dissolution of a clot requites a week or more during normal repair of vascular damage (17). Prevention of irreversible tissue damage during a heart attack requires that a clot, formed by mpture of an atherosclerotic plaque, be dissolved in a matter of hours. This rapid thrombolysis (dissolution of the clot) must be achieved without significant tibrinogenolysis elsewhere in the patient. 

The innermost layer of an artery, which consists of loose connective tissue covered by a monolayer of endothelium that resides on a basement membrane. In human arteries, the intima often contains resident smooth muscle cells even early in life. Atherosclerotic plaques form in the intima. 

Tissue-Specific Expression. In adult rodents, PPAR.a is expressed in liver, kidney, intestine, heart, skeletal muscle, retina, adrenal gland, and pancreas. In adult human, PPARa is expressed in the liver, heart, kidney, large intestine, skeletal muscle (mostly slow-twitch oxidative type I fibers), and in cells of atherosclerotic lesions (endothelial cells, smooth muscle cells, and monocytes/macrophages). Therefore, regardless of... 

PPARa Liver, heart, skeletal muscle, atherosclerotic lesions TG- and LDL-C-lowering and HDL-C-raising re-directs excess cholesterol from the peripheral tissues to the liver for excretion into the bile via HDL-C slowed progression of atherosclerosis Fatty acids, eico-sanoids (fatty acids derived from FAS ) Fibrates fenofibrate (Tricor ), genfibrozil (Lopid ) Dyslipidemia... 

PPARy White adipose tissue, atherosclerotic lesions Insulin-sensitizing and glucoselowering re-directs TG from non-adipose tissues and visceral adipose depots for storage in subcutaneous adipose tissue slowed progression of atherosclerosis Fatty acids, eico-sanoids Th iazolid i ned iones pioglitazone (Actos ), rosiglita-zone (Avandia ) Type 2 diabetes, (insulin resistance, metabolic syndrome)... 

The chemical adducts formed by reaction of aldehydes with lysine residues form highly immunogenic epitopes, and antibodies have been prepared specific for malondialdehyde- and 4-hydroxynonenal-conjugated LDL (Gonen et al., 1987 Yla-Herttuala et al., 1989 Jurgens et al., 1990). These antibodies cross-react with material in atherosclerotic lesions but not normal tissue, thus supporting the central role of lipid peroxidation in the patho nesis of atherosclerosis (Yla-Herttuala et al., 1989, 1991). 

Ischemic heart disease (IHD) is also called coronary heart disease (CHD) or coronary artery disease. The term ischemic refers to a decreased supply of oxygenated blood, in this case to the heart muscle. Ischemic heart disease is caused by the narrowing of one or more of the major coronary arteries that supply blood to the heart, most commonly by atherosclerotic plaques. Atherosclerotic plaques may impede coronary blood flow to the extent that cardiac tissue distal to the site of the coronary artery narrowing is deprived of sufficient oxygen in the face of increased oxygen demand. Ischemic heart disease results from... 

Growing clinical data also points to the importance of IL-8 in atherogenesis. IL-8 has been found in atheromatous lesions from patients with atherosclerotic disease including carotid artery stenosis (103), CAD (118), abdominal aortic aneurysms (AAA) (103,104,114), and peripheral vascular disease (PVD) (104). Furthermore, studies using plaque explant samples have yielded more direct evidence for IL-8 involvement. Media from cultured AAA tissue induced IL-8-dependent human aortic endothelial cell (HAEC) chemotaxis (122). Homocysteine, implicated as a possible biomarker for CAD, is also capable of inducing IL-8 (123-125) by direct stimulation of endothelial cells (123,124) and monocytes (125). When patients with hyperhomocysteinemia were treated with low-dose folic acid, decreases in homocysteine levels correlated with decreases in IL-8 levels (126). Statins significantly decrease serum levels of IL-6, IL-8, and MCP-1, as well as expression of IL-6, IL-8, and MCP-1 mRNA by peripheral blood monocytes and HUVECs (127). Thus, IL-8 may be an underappreciated factor in the pathogenesis of atherosclerosis. 

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. 

Moreau M, Brocheriou I, Petit L, Ninio E, Chapman MJ, Rouis M. Interleukin-8 mediates downregulation of tissue inhibitor of metalloproteinase-1 expression in cholesterol-loaded human macrophages relevance to stability of atherosclerotic plaque. Circulation 1999 99(3) 420-426. 

Tissue distribution of lipo-preparations. The tissue distribution of lipid microspheres in normal and pathologic animals was studied. Research into liposomes of similar size suggested that lipid microspheres accumulated preferentially in the reticuloendothelial system, inflammatory sites, or certain tumors. The distribution of lipid microspheres to these tissues has been found in our studies (7,2). Interestingly, our study showed that lipid microspheres accumulated, particularly at high concentrations, in damaged vascular walls such as atherosclerotic vascular walls. 

HOCl-mediated protein oxidation accelerates under pathophysiological conditions. Thus, proteins from extracellular matrix obtained from advanced human atherosclerotic lesions contained the enhanced levels of oxidized amino acids (DOPA and dityrosine) compared to healthy arterial tissue [44], It was also found that superoxide enhanced the prooxidant effect of hypochlorite in protein oxidation supposedly by the decomposition of chloramines and chlor-amides forming nitrogen-centered free radicals and increasing protein fragmentation [45], In addition to chlorination, hypochlorite is able to oxidize proteins. The most readily oxidized amino acid residue of protein is methionine. Methionine is reversibly oxidized by many oxidants including hypochlorite to methionine sulfide and irreversibly to methionine sulfone [46] ... 

Nixon I don t think cultured cells are like atherosclerotic plaque cells, from what we have seen. In the data you showed on the expression of different channels, the expression and localization of InsP3 receptors is very different. For example, the InsP3 receptor expression around the nuclear envelope is not seen in tissue. 

The evidence for the utility of Cat K inhibition in the treatment of osteoporosis is compelling, but there is mounting evidence that this enzyme may also play a role in other pathologies. Although Cat K is highly expressed in osteoclasts, more recently its expression has been documented in a number of other tissues including, but not limited to, cartilage [25], atherosclerotic plaques [26], adipose... 

The accumulation of apo(a) in the aorta wall and in saphenous vein bypass grafts in relation to Lp(a) levels was recently demonstrated (C14, R3). Subsequently, the preferential deposition of extracellular apo(a) in atherosclerotic lesions of aortic and coronary artery tissue, in conjunction with the intracellular localization of apo(a) in macrophage-derived foam cells, has been the focus of a number of studies (N6, P7, S34, S35, W17). These careful studies also demonstrated the avid binding of Lp(a) to extracellular matrix components and the colocalization of fibrin and apo(a) in atheromatous lesions (N8, W16). 

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