Abstract-Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), encoded by the OLR1 gene, is a scavenger receptor that plays a fundamental role in the pathogenesis of atherosclerosis. LOX-1 activation is associated with apoptosis of endothelial cells, smooth muscle cells (SMCs), and macrophages. This process is an important underlying mechanism that contributes to plaque instability and subsequent development of acute coronary syndromes. Independent association genetic studies have implicated OLR1 gene variants in myocardial infarction (MI) susceptibility. Because single nucleotide polymorphisms (SNPs) linked to MI are located in intronic sequences of the gene, it remains unclear as to how they determine their biological effects. Using quantitative real-time PCR and minigene approach, we show that intronic SNPs, linked to MI, regulate the expression of a new functional splicing isoform of the OLR1 gene, LOXIN, which lacks exon 5. Macrophages from subjects carrying the "non-risk" disease haplotype at OLR1 gene have an increased expression of LOXIN at mRNA and protein level, which results in a significant reduction of apoptosis in response to oxLDL. Expression of LOXIN in different cell types results in loss of surface staining, indicating that truncation of the C-terminal portion of the protein has a profound effect on its cellular trafficking. Furthermore, the proapoptotic effect of LOX-1 receptor in cell culture is specifically rescued by the coexpression of LOXIN in a dose-dependent manner. The demonstration that increasing levels of LOXIN protect cells from LOX-1 induced apoptosis sets a groundwork for developing therapeutic approaches for prevention of plaque instability.

Women are referred for AF ablation later with a more complex clinical pre-operative presentation. Despite this higher risk profile in women, no differences were detected in clinical outcomes. Our findings indicate that CA of AF appears to be safe and effective in women as in men.

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Despite numerous possible risk factors, the most common and consistent predictors of stent thrombosis are early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the principal receptor for oxidized low-density lipoprotein (ox-LDL) in vascular endothelial cells (ECs), has recently been suggested to exert a pivotal role in atherogenesis, possibly by mediating ox-LDL-evoked endothelial dysfunction. On the other hand, LOX-1 expression seems to strongly correlate with the oxidative stress occurring in the vascular wall of experimentally injured blood vessels. Here, we investigated LOX-1 expression and superoxide generation during neointima formation in a balloon injury rat carotid artery model. To test this, we used M40401 [a manganese(II) complex with a bis(cyclo-hexylpyridine-substituted) macrocyclic ligand], a synthetic superoxide dismutase mimetic that is a selective scavenger of superoxide. The injury was performed inserting the balloon catheter through the rat common carotid artery and after 14 days a histopathological analysis revealed a significant restenosis with smooth muscle cell proliferation and neointima formation that was associated with an enhanced expression of LOX-1, nitrotyrosine (the footprint of peroxynitrite) staining, and lipid peroxidation as assessed by malondialdehyde (MDA) formation. Pretreatment of rats with M40401 (0.5-10 mg/kg i.p. daily) reduced neointima formation, MDA accumulation, nitrotyrosine staining, and LOX-1 expression. Here, we show that removal of superoxide formation occurring in injured arteries reduces both neointima formation and LOX-1 expression and that this may represent a novel therapeutical approach in the treatment of vascular disorders in which proliferation of vascular smooth muscle cells and ox-LDL-related endothelial cell dysfunction occur.

Approximately 50% of all acute coronary syndromes occur in previously asymptomatic patients. This study evaluated the value of multislice computed tomography for early detection of significant coronary artery disease (CAD) in high-risk asymptomatic subjects. One hundred sixty-eight asymptomatic subjects with >1 major risk factor (hypertension, diabetes, hypercholesterolemia, family history, or smoking) and an inconclusive or unfeasible noninvasive stress test result (stress electrocardiography, echocardiography, or nuclear scintigraphy) were evaluated in an outpatient setting. After clinical examination and laboratory risk analysis, all patients underwent multislice computed tomographic (MSCT) coronary angiography within 1 week. In all subjects, conventional coronary angiography was also carried out. Multislice computed tomography displayed single-vessel CAD in 16% of patients, 2-vessel CAD in 7%, and 3-vessel CAD in 4%. Selective coronary angiography confirmed the results of multislice computed tomography in 99% of all patients. Sensitivity and specificity of MSCT coronary angiography were 100% and 98%, respectively, with a positive predictive value of 95% and a negative predictive value of 100%. Multislice computed tomographic (MSCT) coronary angiography is a relatively new noninvasive technique to define coronary artery disease (CAD). It is considered 1 of the most significant advances in cardiac imaging technology. Previous studies in symptomatic patients have reported an excellent sensitivity and specificity and negative predictive value of multislice computed tomography, 1-5 much better than those of other noninvasive tests, such as exercise electrocardiography and thallium scintigraphy. 6 -9 However, there are no data available on the extent and severity of CAD in a high-risk asymptomatic population, particularly by noninvasive means. We postulated that multislice computed tomography, if accurate, could be used as a potent noninvasive diagnostic tool to manage patients at high risk for coronary atherosclerosis. 10,11 This study evaluated the value of multislice computed tomography for early detection of significant CAD in asymptomatic subjects with conventional CAD risk factors and inconclusive or unfeasible noninvasive stress test results. MethodsPatient population: We enrolled 168 consecutive asymptomatic subjects from June 2004 to April 2005 (89 men, 27 women; mean age 60 Ϯ 7 years, range 36 to 70) who were evaluated in a primary prevention program in an outpatient setting. All subjects were evaluated with clinical examination and laboratory risk analysis. Criteria for inclusion in this study were an age Ͻ70 years, absence of a previous diagnosis or symptoms of CAD (such as chest pain), presence of Ն1 CAD risk factor, and an inconclusive or unfeasible stress test result (stress electrocardiography, echocardiography, or nuclear scintigraphy). Diagnosis of diabetes was based on criteria of the American Diabetes Association, i.e., symptoms of diabetes plus random plasma glucose concentration Ն200 mg/dl (1...

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