MOESM1 of Cardiopulmonary bypass reduces myocardial oxidative stress, inflammation and increases c-kit+CD45− cell population in newborns

Additional file 1. (1) Information letter to patients and parents, (2) consent form for anonymous publication, participation & storage of medical data and (3) tissue sample form

Flow Diagrams of Study Selection

<div><p>(A) Selection of studies about the handling of CHF patients in placebo-controlled statin trials.</p> <p>(B) Selection of studies about the association between cholesterol levels and mortality in CHF patients.</p> <p>(C) Selection of studies containing original data on statin treatment in patients with established CHF.</p></div

Parvovirus B19-induced vascular damage in the heart is associated with elevated circulating endothelial microparticles

<div><p>Background</p><p>Diagnosis of viral myocarditis is difficult by clinical criteria but facilitated by detection of inflammation and viral genomes in endomyocardial biopsies. Parvovirus B19 (B19V) targets endothelial cells where viral nucleic acid is exclusively detected in the heart. Microparticles (MPs) are released after cell damage or activation of specific cells. We aimed to investigate whether circulating endothelial MPs (EMPs) in human and experimental models of myocarditis are associated with B19V myocarditis.</p><p>Methods</p><p>MPs were investigated in patients with myocarditis (n = 54), divided into two groups: B19V+ (n = 23) and B19V- (n = 31) and compared with healthy controls (HCTR, n = 25). MPs were also investigated in B19V transgenic mice (B19V-NS1+) and mice infected with coxsackievirus B3 (CVB3). MPs were analyzed with fluorescent activated cell sorting (FACS).</p><p>Results</p><p>In human samples, EMP subpopulation patterns were significantly different in B19V+ compared to B19V- and HCTR (p<0.001), with an increase of apoptotic but not activated EMPs. Other MPs such as platelet- (PMPs) leukocyte-(LMPs) and monocyte-derived MPs (MMPs) showed less specific patterns. Significantly different levels of EMPs were observed in transgenic B19V-NS1+ mice compared with CVB3-infected mice (p<0.001).</p><p>Conclusion</p><p>EMP subpopulations are different in B19V+ myocarditis in humans and transgenic B19V mice reflecting vascular damage. EMP profiles might permit differentiation between endothelial-cell-mediated diseases like myocardial B19V infection and other causes of myocarditis.</p></div

Murine endothelial microparticles (CVB3+ infected mice).

<p>Murine endothelial microparticles (EMPs) in CVB3+ infected mice (CVB3+) after 2, 8 and 28 days p.i. compared with controls (C57/Bl6). A: EMPs were increased in CVB3+ mice two days p.i. (p<0.001 vs. control) with a decline in the following 6 days (p<0.001 vs. control) and 28 days p.i. (p<0.001 vs. control). B: The increase of EMPs was due to apoptotic EMPs. C: Activated EMPs were not different between the groups.</p

Murine endothelial microparticles (B19V- transgenic mice).

<p>Murine endothelial microparticles (EMPs) in transgenic B19V-NS1-mice with induction by doxycycline (B19V+) after 2, 4 and 6 weeks p.i. compared with controls (C57/Bl6 and transgenic B19V-NS1 mice without doxycyclin). A: EMPs in C57/Bl6 mice compared to transgenic B19V-NS1-mice without doxycyclin showed about the same EMP numbers (p = 0.775). EMPs were significantly increased in transgenic B19V-NS1-mice with doxycyclin after 2, 4 and 6 weeks compared to controls such as C57/Bl6 (p<0.001) and transgenic B19V-NS1-mice without doxycylin (p<0.001, p = 0.003 and p = 0.029). The increase had its maximum after two weeks with a decline after four weeks. B: The increase of EMPs was due to apoptotic EMPs. C: Activated EMPs were not different between the groups.</p

Clinical parameters of human samples.

<p>Clinical parameters of human samples.</p

Phenotypic characterization of parental strains after six weeks of CCl₄ injections.

<p>Liver fibrosis was assessed by morphometric (A) and biochemical (B) measurement of hepatic collagen (Hyp) contents. Hepatic inflammation was measured by serum ALT activities (C). Sirius red staining of hepatic collagen showed circumferential fibrosis in C57BL/6J mice (D) and pronounced fibrosis in DBA/2J mice (E), corresponding to mean F-scores of 2.0±0.1 and 3.9±0.1, respectively.</p

Chromosomal regions of pQTLs with significant genome-wide LRS values determined by single QTL scans and CIM.

<p>Abbreviations and definitions: <b>pQTL (chr):</b> chromosomal position of quantitative trait locus; <b>LRS (max):</b> likelihood ratio statistic, maximum association between genotype and phenotype variation; <b>SNP (max):</b> single nucleotide polymorphism with maximum LRS in QTL region; <b>1.5 LOD support interval (Mb):</b> chromosomal region in Megabases spanning QTL position; <b>Additive allele effect</b>: estimate of a change in the average phenotype by substitution of one parental allele by another at a given marker position; <b>(−)</b> values indicate an increase of phenotype by C57BL/6J allele, <b>(+)</b> values an increase of phenotype by DBA/2J allele; <b>Dataset:</b> dataset in which the QTL was identified; <b>Hyp</b>: hydroxyproline; CIM: composite interval mapping.</p

Characterization of myocardial tissue in wild type (WT) and TGF-β₁ transgenic mice (TGF-β₁) that have been treated with either metoprolol (METO), telmisartan (TELMI), or soluble TGF-βR-Fc (sR-Fc).

<p>(<b>A</b>) Myocardial TGF-β₁ protein expression as determined by Western blotting in heart homogenates from the various groups as indicated. RasGAP served as lysate control. (<b>B</b>) Body weight, heart weight, and heart/body weight ratio (n = 30–57 animals in each group). (<b>C–F</b>) Morphometric analysis of myocardial tissue (n = 5–9 animals in each group). Shown are the fractional areas of connective tissue (<b>C</b>), cardiac fibroblasts (<b>D</b>), cardiac myocytes (<b>E</b>), and cardiomyocyte diameter (<b>F</b>). *<i>p</i><0.05 vs. WT, ^#<i>p</i><0.05 vs. untreated TGF-β₁ mice.</p

Intima-media thickness measurements in relation to quintiles of serum lathosterol-to-cholesterol, campesterol-to-cholesterol and sitosterol-to-cholesterol.

<p>A: Intima-media thickness measurements in relation to quintiles of lathosterol-to-cholesterol (<i>P = 0.007</i>). Values are mean +/− SEM. B: Intima-media thickness measurements in relation to quintiles of campesterol-to-cholesterol (<i>P<0.001</i>). Values are mean +/− SEM. C: Intima-media thickness measurements in relation to quintiles of sitosterol-to-cholesterol (<i>P<0.001</i>). Values are mean +/− SEM.</p