Endothelial transmigratory cup formation.

<p>Electron micrographs and cartoons of transmigrating wild-type neutrophils where the endothelium forms a transmigratory cup (A, B and C). The arrowheads mark the junctions and L marks the lumen of the blood vessel. e1, e2 and n represent individual endothelial cells and neutrophils respectively. The bar corresponds to 1 µm.</p

Endothelial enscapsulation of transmigrating neutrophils.

<p>Electron micrographs and cartoons of transmigrating wild-type (A) and Mac-1 deficient neutrophils (B). The arrowheads mark the junctions seen in A, the thin endothelial sheet that covers the transmigrating cells is marked with *, e1, e2 and n represent individual endothelial cells and neutrophils respectively. The arrows in B mark gaps in the endothelium, and en marks the endothelial nucleus. Scale bars correspond to 1 µm. The images represent 1 out of 40 analyzed wild-type and 1 out of 24 Mac-1-/- neutrophils. In panel C are presented the percentages of the adherent neutrophils that were covered by endothelial dome-structures.</p

Endothelial dome formation using spinning disk confocal microscopy.

<p>Spinning disk confocal images of MIP-2 superfused cremaster muscle of mice with GFP positive endothelium (green) and GR-1 Alexa Fluor 555 stained neutrophils (red). Panels A and B show adherent neutrophils that have been covered by endothelium. By following the same vessel with two adherent neutrophils over time, dynamic formation of endothelial domes was revealed.</p

Leukocyte recruitment and vascular permeability, 5 nmol/L MIP-2 (A–C) and 0.5 nmol/L MIP-2 (D–F) superfusion.

<p>Leukocyte adhesion (A and D), emigration (B and E) and microvascular permeability increase (C and F) before (time 0) and after addition of MIP-2 (5 nmol/L in A–C and 0.5 nmol/L in D–F) in the superfusate in WT (n = 5 for each concentration) and Mac-1-/- mice (n = 5 for each concentration). Untreated wild-type mice (n = 5) are also included. A leukocyte was considered to be adherent if it remained stationary for more than 30 s, and was quantified as the number of adherent cells within a 100 µm length of venule during 5 min. Leukocyte migration was defined as the number of cells in the extra vascular space within a 200×300 µm area. All values are means±SE. * p<0.05 compared to C57Bl/6 mice receiving similar treatment at the same time-point.</p

Transmigration in respect to endothelial junctions.

<p>The distribution of transmigrating wild-type (n = 40) and Mac-1-/- neutrophils (n = 24) in respect to junctions on electron micrographs.</p

Supplemental Material, Galectin-3_and_CIMT_manuscript_supplementary_tables_only_050418 - Plasma Galectin-3 and Sonographic Measures of Carotid Atherosclerosis in the Atherosclerosis Risk in Communities Study

<p>Supplemental Material, Galectin-3_and_CIMT_manuscript_supplementary_tables_only_050418 for Plasma Galectin-3 and Sonographic Measures of Carotid Atherosclerosis in the Atherosclerosis Risk in Communities Study by Abayomi Oyenuga, Aaron R. Folsom, Oluwaseun Fashanu, David Aguilar, and Christie M. Ballantyne in Angiology</p

Patient-specific flow descriptors and normalised wall index in peripheral artery disease: a preliminary study

<p><i>Background and aims</i>: MRI-based haemodynamics have been applied to study the relationship between time-averaged wall shear stresses (TAWSS), oscillatory shear index (OSI) and atherosclerotic lesions in the coronary arteries, carotid artery and human aorta. However, the role of TAWSS and OSI is poorly understood in lower extremity arteries. The aim of this work was to investigate the feasibility of haemodynamic assessment of the superficial femoral artery (SFA) in patients with peripheral artery disease (PAD) and we hypothesised that there is an association between TAWSS and OSI, respectively, and atherosclerotic burden expressed as a normalised wall index (NWI). <i>Methods</i>: Six cases of 3D vascular geometries of the SFA and related inlet/outlet flow conditions were extracted from patient-specific MRI data including baseline, 12 and 24 months. Blood flow simulations were performed to compute flow descriptors, including TAWSS and OSI, and NWI. <i>Results</i>: NWI was correlated positively with TAWSS (correlation coefficient: <i>r</i> = 0.592; <i>p</i> < 0.05). NWI was correlated negatively with OSI (correlation coefficient: <i>r</i> = −0.310, <i>p</i> < 0.01). Spatially averaged TAWSS and average NWI increased significantly between baseline and 24 months, whereas OSI decreased over two years. <i>Conclusions</i>: In this pilot study with a limited sample size, TAWSS was positively associated with NWI, a measure of plaque burden, whereas OSI showed an inverse relationship. However, our findings need to be verified in a larger prospective study. MRI-based study of haemodynamics is feasible in the superficial femoral artery.</p

Univariate correlations between SPARC and metabolic parameters.

#<p>Univariate correlation analyses were adjusted for gestational age. * p<0.05; ^§ 0.05≤p≤0.1. ^a Skewed distributions were logarithmically transformed for partial Pearson correlation analysis. SPARC, secreted protein acidic and rich in cysteine; FGF21 fibroblast growth factor 21; pre-BMI, pre-pregnancy body mass index; ISI_OGTT: insulin sensitivity index; HOMA-IR, HOMA of insulin resistance index; ALT, alanine transaminase; Cr, Creatinine; TG, triglyceride; TC, total cholesterol; HDL-C, high density lipoprotein cholesterol; LDL-C: low density lipoprotein cholesterol; ApoA1, apolipoprotein A1; ApoB, apolipoprotein B; Lp(a), lipoprotein (a); hsCRP, hypersensitive C reaction protein.</p

Causal Role of Alcohol Consumption in an Improved Lipid Profile: The Atherosclerosis Risk in Communities (ARIC) Study

<div><p>Introduction</p><p>Health benefits of low-to-moderate alcohol consumption may operate through an improved lipid profile. A Mendelian randomization (MR) approach was used to examine whether alcohol consumption causally affects lipid levels.</p><p>Methods</p><p>This analysis involved 10,893 European Americans (EA) from the Atherosclerosis Risk in Communities (ARIC) study. Common and rare variants in alcohol dehydrogenase and acetaldehyde dehydrogenase genes were evaluated for MR assumptions. Five variants, residing in the <i>ADH1B</i>, <i>ADH1C</i>, and <i>ADH4</i> genes, were selected as genetic instruments and were combined into an unweighted genetic score. Triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c) and its subfractions (HDL2-c and HDL3-c), low-density lipoprotein cholesterol (LDL-c), small dense LDL-c (sdLDL-c), apolipoprotein B (apoB), and lipoprotein (a) (Lp(a)) levels were analyzed.</p><p>Results</p><p>Alcohol consumption significantly increased HDL2-c and reduced TG, total cholesterol, LDL-c, sdLDL-c, and apoB levels. For each of these lipids a non-linear trend was observed. Compared to the first quartile of alcohol consumption, the third quartile had a 12.3% lower level of TG (p < 0.001), a 7.71 mg/dL lower level of total cholesterol (p = 0.007), a 10.3% higher level of HDL2-c (p = 0.007), a 6.87 mg/dL lower level of LDL-c (p = 0.012), a 7.4% lower level of sdLDL-c (p = 0.037), and a 3.5% lower level of apoB (p = 0.058, p_overall = 0.022).</p><p>Conclusions</p><p>This study supports the causal role of regular low-to-moderate alcohol consumption in increasing HDL2-c, reducing TG, total cholesterol, and LDL-c, and provides evidence for the novel finding that low-to-moderate consumption of alcohol reduces apoB and sdLDL-c levels among EA. However, given the nonlinearity of the effect of alcohol consumption, even within the range of low-to-moderate drinking, increased consumption does not always result in a larger benefit.</p></div

Sensitivity IV analysis excluding heavy drinkers.

<p>Sensitivity IV analysis excluding heavy drinkers.</p