Oxidative damage to proteins such as apolipoprotein B100 increases the atherogenicity of low density lipoproteins (LDL). However, little is known about the potential oxidative damage to apolipoprotein E (apoE), an exchangeable anti-atherogenic apolipoprotein. ApoE plays an integral role in lipoprotein metabolism by regulating the plasma cholesterol and triglyceride levels. Hepatic uptake of lipoproteins is facilitated by apoE's ability to bind with cell surface heparan sulfate proteoglycans and to lipoprotein receptors via basic residues in its 22 kDa N-terminal domain (NT). We investigated the effect of acrolein, an aldehydic product of endogenous lipid peroxidation and a tobacco smoke component, on the conformation and function of recombinant human apoE3-NT. Acrolein caused oxidative modification of apoE3-NT as detected by Western blot with acrolein-lysine-specific antibodies, and tertiary conformational alterations. Acrolein-modification impairs the ability of apoE3-NT to interact with heparin and the LDL receptor. Furthermore, acrolein-modified apoE3-NT displayed a 5-fold decrease in its ability to interact with lipid surfaces. Our data indicate that acrolein disrupts the functional integrity of apoE3, which likely interferes with its role in regulating plasma cholesterol homeostasis. These observations have implications regarding the role of apoE in the pathogenesis of smoking-and oxidative stress-mediated cardiovascular and cerebrovascular diseases. KeywordsCardiovascular disease; apolipoprotein E; acrolein; tobacco smoke; oxidative stress; aging; LDL receptor; heparan sulfate proteoglycan; lysine modification Oxidative stress is recognized as a major factor in the onset of atherosclerosis, cardiovascular disease and stroke in humans; of several factors that lead to increased oxidative stress, aging and life style (diet, smoking) play crucial roles. Atherosclerosis is characterized by the intracellular and extra cellular deposition of low density lipoproteins (LDL) in macrophages (1). Oxidative modification of plasma LDL leads to their uptake by scavenger receptors located The role of apoE in cholesterol metabolism emerged from studies with transgenic mice over expressing apoE, which manifested decreased plasma cholesterol levels on a chow diet and a marked resistance to hypercholesterolemia when fed a cholesterol rich diet (4). On the other hand, apoE-deficient subjects develop symptoms of type III hyperlipoproteinemia (5), with elevated plasma cholesterol levels and accumulation of particles bearing size in the very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) range (6,7). Further, inactivation of apoE by gene targeting leads to accumulation of cholesterol-rich remnant lipoproteins and spontaneous atherosclerotic lesions in mice (8,9). Taken together, these early studies have established the key role of apoE in regulating plasma cholesterol and triglyceride levels, which are recognized as indicators of heart disease. The focus of this study is to investigate the role ...

We evaluated two children with pulmonary atresia for coil embolization of aortopulmonary collateral vessels after placement of palliative aortopulmonary shunts. To determine vessel distribution and lung perfusion prior to collateral embolization, perfusion scintigraphy with technetium 99m-labeled macroaggregated albumin assessed pulmonary blood flow before and after balloon wedge catheter occlusion of the collaterals. In the first patient we found no perfusion defect during collateral occlusion, and we proceeded with embolization. In the second child, perfusion scintigraphy during occlusion of the collateral vessels demonstrated a filling defect, and embolization was not performed, thus avoiding the creation of a potential perfusion defect in this patient. Assessing the physiologic significance of aortopulmonary collateral vessels by utilizing temporary balloon occlusion of the collateral vessels and concurrent perfusion scintigraphy as an adjunct to selective angiography can provide a significant contribution to the safety and accuracy of coil embolization.