Atherosclerosis lysophosphatidylcholine

Plasma and urine samples from atherosclerotic and control rats were comparatively analyzed by ultrafast liquid chromatography coupled with ion trap-time-of-flight (IT-TOF) MS (UFLC-IT/TOF-MS) (16). They identified 12 metabolites in rat plasma and 8 metabolites in rat urine as potential biomarkers. Concentrations of leucine, phenylalanine, tryptophan, acetylcar-nitine, butyrylcamitine, propionylcamitine, and spermine in plasma and 3-0-methyl-dopa, ethyl /V2-acety I -1. -argininate, leucylproline, glucuronate, A(6)-(A-threonylcarbonyl)-adenosine, and methyl-hippuric acid in urine were decreased in atherosclerosis rats ursodeoxycholic acid, chenodeoxycholic acid, LPC (06 0), LPC (08 0), and LPC (08 1) in plasma and hippuric acid in urine were increased in atherosclerosis rats. The altered metabolites demonstrated abnormal metabolism of phenylalanine, tryptophan, bile acids, and amino acids. Lysophosphatidylcholine (LPC) plays an important role in inflammation and cell proliferation, which shows a relationship between LPC in the progress of atherosclerosis and other inflammatory diseases. 

Lipoprotein associated phospholipase A2(LpPLA2> is a serine dependent lipase of novel structure which is associated with the presence of LDL in plasma. It hydrolyses oxidised phospholipids to generate lysophosphatidylcholine and oxidised free fatty acids (Scheme 1), both of which are potent chemoattractants for circulating monocytes. Accumulation of lysophosphatidylcholine results in macrophage proliferation and the endolithial dysfunction observed in patients with atherosclerosis. Inhibition of LpPLA2 would thus be expected to stop plaque build-up and provide an attractive strategy in the treatment of atherosclerosis. 

Risk and protective factors of atherosclerosis influence VCAM-1 expression [10,19]. A possible relation between VC AM expression and oxidized LDL was established when an important component of this modified lipoprotein, lysophosphatidylcholine, was shown to stimulate VCAM expression and increase adhesion of monocytes on endothelium in cell cultures [10,18,19]. Modified LDL and its constituents augment c)4 okine-activated VCAM-1 expression in human vascular endothelial cells [10,20]. In contrast, HDL inhibits cytokine-induced expression of endothelial cell adhesion molecules [10,21]. -3 Fatty acids have been found to decrease mRNA levels and surface expression of VCAM-1 in endothelial cells [10,22]. Aspirin inhibits induction of mRNA and cell surface expression of VCAM-1 by TNF-a and thereby inhibits monocyte adhesion on stimulated endothelial cells [10,23]. In contrast to ICAM-1, E-selectin, and P-selectin, endothelial VCAM-1 can mediate leukocyte adhesion via its sole interaction with the integrins 4P1 or 4P7 [10]. 

Hsieh, C C, Yen, M H, Liu, H W, and Lau, Y T, Lysophosphatidylcholine induces apoptotic and non-apoptotic death in vascular smooth muscle cells In comparison with oxidized LDL, Atherosclerosis 151 (2000) 481-491. 

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. 

LDL is one of the major carriers of cholesterol in circulation. LDL is also known as a bad lipoprotein due to the fact that LDL transports cholesterol and other fat molecules to peripheral tissues (i.e. arterial walls) and plays a crucial role in the development of several cardiovascular-related diseases such as atherosclerosis, stroke, and myoeardial infarction. Oleic acid and lysophosphatidylcholine (Figure 5) are the major constituents of LDL. Oxidized LDL (ox-LDL) is rapidly engulfed by macrophages to induce foam cell formation in the arterial wall [37]. Therefore, ox-LDL is thought to be one of the major contributors to the development of atherosclerosis. Moreover, ox-LDL can enhance coronary vasospasm (vasoconstriction) via induce endotheliinn-dependent vasoconstriction consequently preventing vasodilation and increase the activity of protein kinase C isoforms a and 8 in VSMCs of porcine coronary arteries [38-40]. 

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