4-hydroxy-2-nonenal and Thrombosis

Basic research, exploring the hypothesis that γ-hydroxyalkenal phospholipids are generated in vivo through oxidative cleavage of polyunsaturated phospholipids, is delivering a bonanza of molecular mechanistic insights into cardiovascular disease. Rather than targeting a specific pathology, these studies were predicated on the presumption that a fundamental understanding of lipid oxidation is likely to provide critical insights into disease processes. This investigational approach, from the chemistry of biomolecules to disease phenotype, that complements the more common opposite paradigm, is proving remarkably productive.

Topics: Aldehydes; Animals; Biological Transport; Cardiovascular Diseases; CD36 Antigens; Coronary Vessels; Free Radicals; Heart; Hepatocytes; Humans; Lipid Metabolism; Lipoproteins, LDL; Lysophosphatidylcholines; Mice; Monocytes; Neovascularization, Pathologic; Oxidation-Reduction; Phagocytosis; Protein Processing, Post-Translational; Scavenger Receptors, Class B; Spectrometry, Mass, Electrospray Ionization; Thrombosis; Toll-Like Receptor 2

Increased reactive oxygen species (ROS) and hyperlipidemia can promote arterial thrombus. We evaluated the potential of a partially hydrolyzed guar gum (PHGG) as dietary fiber on lipid profiles and FeCl3-induced arterial thrombosis in the high fat-diet fed hamsters. Our in vitro results found that PHGG is efficient to scavenge O2-*, H2O2, and HOCl. High fat-diet increased plasma triglyceride, total cholesterol, LDL, VLDL, methylguanidine and dityrosine level and accelerated FeCl3-induced arterial thrombosis formation (from 463 +/- 51 to 303 +/- 45 sec). Low dose PHGG supplement significantly decreased the total cholesterol, LDL, methylguanidine and dityrosine level and delayed the time for arterial thrombosis formation (528 +/- 75 sec). High dose PHGG supplement decreased the level in triglyceride, total cholesterol, LDL and VLDL and further delayed the time for arterial thrombus (671 +/- 36 sec). The increased Bax protein and decreased Bcl-2 and HSP-70 protein expression was found in the carotid and femoral arteries of high fat-diet hamsters. Low and high dose of PHGG supplement decreased Bax expression and increased Bcl-2 and HSP-70 protein expression. We found that FeCl3 significantly enhanced intercellular adhesion molecule-1 and 4-hydroxynonenal expression in the endothelial site of damaged artery after 150-sec FeCl3 stimulation. PHGG supplement decreased the endothelial ICAM-1 and 4-hydroxynonenal expression after 150-sec FeCl3 stimulation. Based on these results, we conclude that PHGG supplement can increase antioxidant protein expression and thus decrease oxidative stress induced arterial injury.

Topics: Aldehydes; Animals; Antioxidants; Arteries; bcl-2-Associated X Protein; Body Weight; Carbohydrate Conformation; Carbohydrate Sequence; Cricetinae; Dietary Fats; Dietary Supplements; Eating; Free Radical Scavengers; Galactans; HSP70 Heat-Shock Proteins; Humans; Intercellular Adhesion Molecule-1; Iron Compounds; Lipids; Male; Mannans; Mesocricetus; Molecular Sequence Data; Molecular Structure; Oxidative Stress; Plant Gums; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Thrombosis