Background-HDL cholesterol levels are inversely correlated with coronary heart disease risk in humans, and in animal studies, HDL elevation decreases formation and progression of foam-cell lesions. The potential for HDL to affect preexisting advanced atherosclerotic lesions is not known. To approach this issue, we used a novel mouse aortic transplantation model. Methods and Results-ApoE-deficient (EKO) mice were fed a Western-type diet for 6 months, and thoracic aortic segments containing advanced lesions replaced segments of the abdominal aorta of 4-month-old EKO syngeneic mice not expressing (plasma HDL cholesterol Ϸ26 mg/dL) or expressing (HDL Ϸ64 mg/dL) a human apoAI (hAI) transgene. Immunostaining for CD68 and other macrophage-associated proteins, monocyte chemoattractant protein-1, acyl coenzyme A:cholesterol acyltransferase, and tissue factor, in lesions of pretransplant and EKO recipient mice showed abundant macrophages. In contrast, compared with any other group, lesional macrophage area in hAI/EKO mice decreased Ͼ80% (PϽ0.003), and smooth muscle cell content (␣-actin staining) increased Ͼ300% (PϽ0.006). The decrease in macrophages and increase in smooth muscle cells was primarily in the superficial subendothelial layer. Conclusions-Increasing HDL cholesterol levels in EKO mice retards progression of advanced atherosclerotic lesions and remodels them to a more stable

Objective-Protective properties of high-density lipoproteins (HDL) may include reverse cholesterol transport and suppression of oxidation and inflammation. These were investigated in vivo, as were the effects of HDL on the characteristics of atherosclerotic lesions. Methods and Results-Male apolipoprotein E knockout (apoEϪ/Ϫ) and apoEϪ/Ϫ mice expressing human apolipoprotein AI (hAI/apoEϪ/Ϫ) were studied up to 20 weeks after commencing a high-fat diet. Plasma HDL cholesterol was twice as high in hAI/apoEϪ/Ϫ mice. Over time, aortic root lesion area remained less in hAI/apoEϪ/Ϫ mice, although plaques became complex. In advanced lesions, plaque lipid was higher in apoEϪ/Ϫ mice, whereas plaque collagen and alpha actin were increased in hAI/apoEϪ/Ϫ mice. In nonlesional aorta, mRNA abundance for pro-inflammatory proteins Key Words: high-density lipoproteins Ⅲ mice Ⅲ atherosclerosis Ⅲ inflammation P lasma high-density lipoprotein (HDL) cholesterol concentration is inversely related to the development of ischemic heart disease and its complications. 1,2 Comparatively little is known, however, of exactly how HDL exerts this protection. In particular, it is not known whether higher plasma HDL alters plaque composition, or whether HDL simply retards temporally lesion progression.A limitation to examining directly the effects of HDL in animal models has been the difficulty in sustaining the elevation of HDL. One successful approach has been the transgenic expression of human apolipoprotein A-I (hAI), which elevates HDL and retards the development of atherosclerosis in C57Bl6 mice fed atherogenic diet 3 and in apolipoprotein E-deficient (apoEϪ/Ϫ) mice fed normal chow. 4 Under the conditions in those studies, however, mice did not develop lesions beyond the foam cell stage, leaving open the question of the effects of HDL on the development of advanced lesions, more relevant to human atherosclerosis.Rong et al have reported that elevating HDL retards the progression and favorably alters the composition of preexisting complex lesions, 5 whereas Shah et al have shown that injection of a single high dose of apoA-I Milano regressed established lesions in mice with advanced aortic atherosclerosis. 6 Recently, decreased plaque size has been demonstrated in low-density lipoprotein (LDL) receptordeficient mice in which HDL elevation was attained through adenovirus-mediated hAI expression. 7 The present study in apoEϪ/Ϫ mice fed high-fat, high-cholesterol Western diet (WD) provides the first systematic examination of the quantitative effects of lifelong sustained elevation of HDL on the composition of lesions across a wide range of severity, and tests the efficacy of HDL to retard lesion progression in the face of higher levels of non-HDL cholesterol than previously studied.Atherosclerotic plaques contain oxidized LDL (OxLDL) as recognized by antibodies against oxidatively modified groups such 10 Mice lacking paraoxonase show increased susceptibility to atherosclerosis, 11 whereas adenovirus-mediated gene transfer of human platelet ...

Introduction Expert interpretation of modern noninvasive neuroimaging such as CTA or MRA should detect nearly all aneurysms responsible for an isolated third nerve palsy. Whether a catheter angiogram should still be obtained in cases with negative CTA or MRA remains debated, and mostly relies on whether the noninvasive study was correctly performed and interpreted. The aim of our study was to review the diagnostic strategies used to evaluate patients with isolated aneurysmal third nerve palsy at a large academic center. Methods Retrospective review of all cases with posterior communicating artery (PCom A) aneurysmal third nerve palsies seen at our institution since 2001. Results We identified 417 cases with third nerve palsy, aneurysm, or subarachnoid hemorrhage, among which 17 presented with an acute isolated painful third nerve palsy related to an ipsilateral PCom A aneurysm (mean age 52; range 33–83 years). Patients were classified into 3 groups based on the results of the noninvasive imaging obtained at initial presentation. Group I included 4 cases with subarachnoid hemorrhage on initial non-contrast head CT initially obtained in an emergency department for evaluation of their isolated third nerve palsy. Group II included 5 cases with isolated third nerve palsy and normal non-contrast head CT at presentation, immediately correctly diagnosed with a PCom A aneurysm at the referring institution. Group III included the 8 remaining cases who all had aneurysms that were missed on noninvasive studies at outside institutions. Review of these outside studies at our institution showed a PCom A aneurysm, confirming misinterpretation of these tests by the outside radiologists, rather than inadequate technique. Absence of specific training in neuroradiology and inaccurate clinical information provided to the interpreting radiologist were associated with test misinterpretation at the outside institutions. The average size of PCom A aneurysms causing an isolated third nerve palsy across all 3 groups was 7.3 mm, and was similar in each group. Conclusion Our study suggests that aside from an accurate history, the training and experience of the interpreting radiologist is probably the most important factor in determining the reliability of a noninvasive scan in patients with isolated third nerve palsies.