Endothelial cells atherosclerosis

Tribolo S, Lodi F, Connor C, Suri S, Wilson VG, Taylor MA, Needs PW, Kroon PA, Hughes DA. 2008. Comparative effects of quercetin and its predominant human metabolites on adhesion molecule expression in activated human vascular endothelial cells. Atherosclerosis 197 50-56. 

Eue I, Sorg C. 2001. Arachidonic acid specifically regulates binding of S100A8/9, a heterodimer complex of the S100 class of calcium binding proteins, to human microvascular endothelial cells. Atherosclerosis 154(2) 505—508. 

Nomura S, Tandon NN, Nakamura T, Cone J, Fukuhara S, Kambayashi J. High-shear-stress-induced activation of platelets and microparticles enhances expression of cell adhesion molecules in THP-1 and endothelial cells. Atherosclerosis 2001 158 277-287. 

Kaneta S, Satoh K Kano S, et al. All hydrophobic HMG-CoA reductase inhibitors induce apoptotic death in rat pulmonary vein endothelial cells. Atherosclerosis, 2003, 170, 237-243. 

Tamagaki T, Sawada S, Imamura H, Tada Y, Yamasaki S, Toratani A, Sato T, Komatsu S, Akamatsu N, Yamagami M, Kobayashi K, Kato K, Yamamoto K, Shirai K, Yamada K, Higaki T, Nakagawa K, Tsuji H, Nakagawa M (1996) Effects of high-density lipoproteins on intracellular pH and proliferation of human vascular endothelial cells. Atherosclerosis 123 73-82... 

Mayol V, Duran MJ, Gerbi A, Dignat-George F, Levy S, Sampol J, et al. Cholesterol and omega-3 fatty acids inhibit Na, K ATPase activity in human endothelial cells. Atherosclerosis 1999 142 327-333. 

Matsubara, M and Hasegawa, K, Benidipine, a dihydropyridine-calcium channel blocker, prevents lysophosphatidylcholine-induced injury and reactive oxygen species production in human aortic endothelial cells. Atherosclerosis 178 (2005) 57-66. 

Inoue, N., Takeshita, S., Gao, D., Ishida, T., Kawashima, S., Akita, H., Tawa, R., Sakurai, H., and Yokoyama, M., Lysophosphatidylcholine increases the secretion of matrix metalloproteinase 2 through the activation of NADH/NADPH oxidase in cultured aortic endothelial cells. Atherosclerosis, 155, 45-52,2001. 

Frostegard, J., Haegerstrand, A., Gidlund, M., and Nilsson, J. (1991). Biologically modified LDL increases the adhesive properties of endothelial cells. Atherosclerosis 90, 119-126. 

Ganji, S.H., Qin, S., Zhang, L., Kamanna, V.S., and Kashyap, M.L., 2009. Niacin inhibits vascular oxidative stress, redox-sensitive genes, and monocyte adhesion to human aortic endothelial cells. Atherosclerosis. 202 68-75. 

Evidence from cellular studies in vitro initially showed how oxidative processes could play a central role in the pathological changes involved in the genesis of atherosclerosis. LDL can be oxidatively modified in culture by a range of cell types including endothelial cells (Henriksen et a.1., 1981), arterial smooth muscle cells... 

Oxidatively modified LDL up-regulates the surfece expression of VCAM-1 and intracellular adhesion molecule-1 (ICAM-1) in cultured endothelial cells, promoting the interactions between both cell types (Kume et al., 1992). This may play a pivotal role in the development of atherosclerosis by promoting the penetration of circulating monocytes into the suben-dothelial space whilst inhibiting the mobility of resident macrophages. It has been previously demonstrated that ICAM-1, E-selectin, and VCAM-1 are up-regulated in the microvasculature of rheumatoid but not control synovium (Corkill et al., 1991 Koch et al., 1991). The association between ox-LDL and increased expression of adhesion molecules in the inflamed synovium has yet to be studied. 

Fig. 2. The role of MCP-1 (CCL2)/CCR2 in atherosclerosis is thought to occur through the response of endothelial cells and vascular smooth muscle cells to oxidized lipoproteins. After injury by oxidized lipoproteins, MCP-1 is released and attracts CCR2-expressing monocytes to the site of injury and activates them to secrete inflammatory mediators.

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. 

Contrary to LDL, high-density lipoproteins (HDL) prevent atherosclerosis, and therefore, their plasma levels inversely correlate with the risk of developing coronary artery disease. HDL antiatherogenic activity is apparently due to the removal of cholesterol from peripheral tissues and its transport to the liver for excretion. In addition, HDL acts as antioxidants, inhibiting copper- or endothelial cell-induced LDL oxidation [180], It was found that HDL lipids are oxidized easier than LDL lipids by peroxyl radicals [181]. HDL also protects LDL by the reduction of cholesteryl ester hydroperoxides to corresponding hydroperoxides. During this process, HDL specific methionine residues in apolipoproteins AI and All are oxidized [182]. 

H11. Hajjar, K. A., Gavish, D., Breslow, J. L., and Nachman, R. L., Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature (London) 339, 303-305 (1989). 

K7. Karmansky, I., and Gruener, N., Roles of immobilized proteins and lipoprotein (a) in adhe-sivity of endothelial cells Possible implication for atherosclerosis. Cell Biol. Int. Rep. 16, 503-515 (1992). 

The ACE gene encodes two isozymes (somatic ACE isozyme and germinal ACE isozyme). ACE is a membrane-bound enzyme on the surface of vascular endothelial cells that also circulates in plasma and shows great individual variability determined by an I/D polymorphism in intron 16 of the ACE gene (ACE-I/D polymorphism). More than 160 ACE polymorphisms have been reported, 34 of which are located in coding regions, and 18 are missense mutations (606). ACE-related polymorphic variants have been associated with hypertension, atherosclerosis, stroke, left ventricular hypertrophy, chronic renal failure in IgA nephropathy, Henoch-Schonlein purpura nephritis, mechanical efficiency of skeletal muscle, intracranial aneurysms, susceptibility to myocardial infarction, diabetic nephropathy, AD, and longevity (12,606,607). 

Even during the first or second decade of life, small deposits of lipid, fatty streaks, are often detectable in arterial walls. In a study by R. Ross over half of the children (age 10-14) examined at autopsy had fatty streaks in their arteries. These are the first indications of the entry of fat and cholesterol into macrophages in the subendothelial space of an artery. This initiates a sequence of processes that eventually produces a plaque. A prerequisite for the development of fatty streaks, and hence atherosclerosis, is injury to the endothelial cells fining the arterial wall. Many factors are suspected of causing this, including pollutants. 

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