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Atherosclerosis arises from leukocyte infiltration and thickening of the artery walls and constitutes a major component of vascular disease pathology, but the molecular events underpinning this process are not fully understood. Proteins containing an Asn-Gly-Arg (NGR) motif readily undergo deamidation of asparagine to generate isoDGR structures that bind to integrin αvβ3 on circulating leukocytes. Here we report the identification of isoDGR motifs in human atherosclerotic plaque components including extracellular matrix (ECM) proteins fibronectin and tenascin C, which have been strongly implicated in human atherosclerosis. We further demonstrate that deamidation of NGR motifs in fibronectin and tenascin C leads to increased adhesion of the monocytic cell line U937 and enhanced binding of primary human monocytes, except in the presence of a αvβ3-blocking antibody or the αv-selective inhibitor cilengitide. In contrast, under the same deamidating conditions monocyte-macrophages displayed only weak binding to the alternative ECM component vitronectin which lacks NGR motifs. Together, these findings confirm a critical role for isoDGR motifs in mediating leukocyte adhesion to the ECM via integrin αvβ3 and suggest that protein deamidation may promote the pathological progression of human atherosclerosis by enhancing monocyte recruitment to developing plaques.

AIM:To investigate the clinical features and in-hospital outcomes of young adults with acute myocardial infarction (AMI) in Singapore. METHODS:Between January 2005 to September 2010, 333 consecutive patients aged ≤ 45 years old were diagnosed to have AMI at our institution. As Singapore is a multi-ethnic society, we also analysed whether ethnic differences exist between the three dominant ethnic groups, Malay, Chinese and Indian with regards to the clinical features. Clinical data was collected retrospectively on demographic characteristics, presenting signs and symptoms, blood investigation, angiographic findings and in-hospital clinical outcomes. RESULTS:The mean age at presentation was 40.2 ± 4.0 years with male predominance (94%). The majority of patients were Chinese (51%) followed by Indians (31%) and Malays (18%). The most common risk factor was smoking (74%) followed by hypertension (28.5%) and hyperlipidemia (20.0%). 37% of patients were obese. The majority of patients had single vessel disease (46%) on coronary angiography. The mean total cholesterol, low-density lipoprotein and highdensity lipoprotein levels were 5.6 ± 1.2 mmol/L, 3.8 ± 1.1 mmol/L and 0.93 ± 0.25 mmol/L respectively. The mean left ventricular function was 44% ± 10% with the incidence of heart failure 3% and cardiogenic shock 4.5%. Overall in-hospital mortality was low with 4 deaths (1.2%). For ethnic subgroup analysis, Indians have a 3-fold risk of developing premature AMI when compared to other ethnic groups. CONCLUSION:Young AMI patients in Singapore are characterized by male predominance, high incidence of smoking and obesity. Overall in-hospital clinical outcomes are favourable. Among the 3 ethnic groups, Indians have the highest risk of developing premature AMI.

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