Replication of Putative Susceptibility Loci from Genome-Wide Association Studies Associated with Coronary Atherosclerosis in Chinese Han Population

BACKGROUND: Coronary atherosclerosis, the main cause of cardiovascular disease, is a progressive disease. Recent Genome Wide Association Studies (GWASs) discovered several novel loci associated with coronary artery disease (CAD) or its main complication myocardial infarction (MI). In this study, we investigated the associations between previously reported CAD- and MI-associated variants and coronary atherosclerosis in Chinese Han population. METHODOLOGY/PRINCIPAL FINDINGS: We performed a case-control association study with 2,335 coronary atherosclerosis patients and 1,078 controls undergoing coronary angiography of Chinese Han from China. Fourteen single nucleotide polymorphisms (SNPs), located at 1p13.3, 1q41, 2q36.3, 6q25.1, 9p21.3, 10q11.21 and 15q22.33, were genotyped in our sample collection. Six SNPs at 9p21 were associated with coronary atherosclerosis susceptibility (P(trend)<0.05) and rs10757274 showed the most significant association (P = 2.38×10(-08), OR = 1.34). These associations remained significant after adjustment for multiple comparisons. Rs17465637 at 1q41 (P(trend) = 6.83×10(-03), OR = 0.86) also showed significant association with coronary atherosclerosis, but the association was not significant after multiple comparisons. Additionally, rs501120 (P = 8.36×10(-03), OR = 0.80) at 10q11.21 was associated with coronary atherosclerosis in females, but did not show association in males and all participants. Variants at 1p13.3, 2q36.3, 6q25.1 and 15q22.33 showed no associations with coronary atherosclerosis and main cardiovascular risk factors in our data. CONCLUSIONS/SIGNIFICANCE: Our findings indicated variants at 9p21 were significantly associated with coronary atherosclerosis in Han Chinese. Variants at 1q41 showed suggestive evidence of association and variants at 10q11.21 showed suggestive evidence of association in females, which warrant further study in a larger sample

The stromal cell-derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques

Chemokines are chemotactic cytokines that activate and direct the migration of leukocytes. However, their role in modulating platelet function has not been shown. We studied the direct effect of chemokines on human platelets and found that of the 16 tested only stromal cell-derived factor (SDF)-1 induced platelet aggregation, accompanied by a rise in intracellular calcium. Platelets expressed the SDF-1 receptor, CXCR4, and an antibody to CXCR4 and pertussis toxin inhibited SDF-1-induced platelet aggregation, confirming that this effect is mediated through CXCR4, a Galphai-coupled receptor. SDF-1-induced platelet aggregation was also inhibited by wortmannin, LY294002, and genistein, suggesting that phosphatidylinositol 3-kinase and tyrosine kinase are likely involved in SDF-1-induced platelet aggregation. Because chemokines are produced from multiple vascular cells and atherosclerotic vessels are prone to develop platelet-rich thrombi, we examined the expression of SDF-1 in human atheroma. SDF-1 protein was highly expressed in smooth muscle cells, endothelial cells, and macrophages in human atherosclerotic plaques but not in normal vessels. Our studies demonstrate a direct effect of a chemokine in inducing platelet activation and suggest a role for SDF-1 in the pathogenesis of atherosclerosis and thrombo-occlusive diseases

Evaluation of how users interface with holographic augmented reality surgical scenes: Interactive planning MR-Guided prostate biopsies

Background User interfaces play a vital role in the planning and execution of an interventional procedure. The objective of this study is to investigate the effect of using different user interfaces for planning transrectal robot-assisted MR-guided prostate biopsy (MRgPBx) in an augmented reality (AR) environment. Method End-user studies were conducted by simulating an MRgPBx system with end- and side-firing modes. The information from the system to the operator was rendered on HoloLens as an output interface. Joystick, mouse/keyboard, and holographic menus were used as input interfaces to the system. Results The studies indicated that using a joystick improved the interactive capacity and enabled operator to plan MRgPBx in less time. It efficiently captures the operator's commands to manipulate the augmented environment representing the state of MRgPBx system. Conclusions The study demonstrates an alternative to conventional input interfaces to interact and manipulate an AR environment within the context of MRgPBx planning

Suppressive effect of combination treatment of leflunomide and methotrexate on chemokine expression in patients with rheumatoid arthritis

To study the immunosuppressive and anti-inflammatory effects of combined leflunomide and methotrexate (MTX) therapy on chemokine expression in patients with rheumatoid arthritis (RA), nine patients were enrolled for the combination therapy for 24 weeks. These patients have been on treatment with MTX 15 mg/week for not less than 3 months before entry to the study. A loading dose of l00 mg/day of leflunomide was given for 3 days, followed by 10 mg/day for the rest of the study period. Plasma concentrations of monocyte chemotactic protein-1 (MCP-1), thymus- and activation-regulated chemokine (TARC), and macrophage-derived chemokine (MDC) were assayed before and after combination treatment by ELISA. Gene expression of inflammatory cytokines and chemokines of peripheral blood mononuclear cells was analysed by cDNA expression array. Plasma MCP-1, TARC and MDC concentrations were significantly lower in patients after combination treatment [median (interquartile range) before versus after treatment: MCP-1 of 118·0 (64·0–515·2) versus 3·2 (0·0–22·8) pg/ml, P < 0·01; TARC of 126·1 (27·2–197·4) versus 0·0 (0·0–52·5) pg/ml, P < 0·05; MDC of 503·3 (446·2–600·9) versus 366·8 (337·4–393·4) pg/ml, P < 0·05]. Positive correlations among reductions in plasma chemokines and clinical outcome measures were also found. Expression of chemokine genes including MDC and TARC was suppressed after combination treatment [% suppression of 38·7 (54·3–13·0) and 53·7 (55·9–28·4), respectively]. Combination therapy with leflunomide and MTX exhibits anti-inflammatory activity in the suppression of chemokine expression and subsequent recruitment of inflammatory cells into the inflammatory sites in RA