Multi-biomarker strategy for prediction of myocardial dysfunction and mortality in sepsis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#The present study was to evaluate the feasibility of using the multi-biomarker strategy for the prediction of sepsis-induced myocardial dysfunction (SIMD) and mortality in septic patients.@*METHODS@#Brain natriuretic peptide (BNP), cardiac troponin I (cTnI), and heart-type fatty acid-binding protein (h-FABP) in 147 septic patients were assayed within 6 h after admission. We also determined the plasma levels of myeloperoxidase (MPO) and pregnancy-associated plasma protein-A (PAPP-A). The receiver operating characteristic (ROC) curve was used to assess the best cutoff values of various single-biomarkers for the diagnosis of SIMD and the prediction of mortality. Also, the ROC curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) indices were used to evaluate the feasibility of using multi-biomarkers to predict SIMD and mortality.@*RESULTS@#Our statistics revealed that only h-FABP independently predicted SIMD (P0.05). A history of shock and MPO were independent predictors of mortality in septic patients (both P0.05).@*CONCLUSIONS@#The findings of this study indicate that a sensitive and specific strategy for early diagnosis of SIMD and mortality prediction in sepsis should incorporate three biomarkers.

Relationship between endothelial-to-mesenchymal transition and cardiac fibrosis in acute viral myocarditis / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the relationship between endothelial-to-mesenchymal transition (EndMT) and myocardial fibrosis in acute viral myocarditis (VMC).</p><p><b>METHODS</b>Twenty-eight Balb/c mice were randomized into 3 groups: control group (n=8), VMC group(n=10) and intervention group(n=10). Mice in VMC and intervention groups were injected intraperitoneally(i.p) with single dose of coxsackievirus B3, mice in control group were injected with equal amount of viral-free vehicle. In the following day, mice in control and VMC groups were injected i.p with 0.1 ml of saline and intervention group with 0.1 ml of recombinant human bone morphogenetic protein 7(rh-BMP7) at a concentration of 300 μg/kg. The mice hearts were harvested after 7 d, cardiac collagen volume fraction (CVF) was calculated on picrosirius red-stained sections. mRNA and protein expression of TGF-β1, CD31, VE-cadherin, fibroblast special protein 1 (FSP-1) and α-smooth muscle actin (α-SMA) and collagen 1α1 in myocardiac tissues were detected by real-time RT-PCR and Western blot analysis, respectively.</p><p><b>RESULTS</b>Compared to controls, overt fibrosis was presented in necrotic area of myocardium in VMC group. Meanwhile, marked increase of TGF-β1 expression accompanied with EndMT characterized by loss of endothelial phenotype (decreased expression of CD31 and VE-cadherin), gain of mesenchymal proteins (overexpression of FSP-1 and α-SMA) and increased synthesis of collagen was also demonstrated. Both EndMT and cardiac fibrosis were simultaneously reversed by TGF-β1 inhibition.</p><p><b>CONCLUSION</b>EndMT is involved in cardiac fibrosis in acute viral myocarditis, TGF-β1 might be a main mediator.</p>

Effect of astragaloside on myocardial fibrosis in chronic myocarditis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of astragaloside (Astr), one of the active components of the Chinese medical herb Astragulus membranaceus, on cardiac fibrosis in chronic myocarditis and its relevant mechanisms.</p><p><b>METHODS</b>Eighty mice were randomized into 3 groups, the control group (n=20), the model group (n=30) and the Astr group (n=30). Mice in the model group and the Astr group were monthly intraperitoneally inoculated with CVB3, but to the control group equal amount of culture fluid was given instead. Mice in the control and the model group were fed with drinking water while those in the Astr group with drinking water containing Astr-sodium carboxymethycellulose at a concentration of 300 mg/L. All the survived mice were sacrificed 3 months later. Heart tissue of mice was stained by picrosirius red for calculating collagen volume fraction (CVF) with an automatic image analysis system. Expressions of transforming growth factor beta1 (TGF-beta1), platelet derived growth factor (PDGF), matrix metalloproteinase 1 (MMP-1), tissue inhibitor of metalloproteinase 1 (TIMP-1), MMP-13 and MMP-14 in heart tissue were detected by Western blot analysis.</p><p><b>RESULTS</b>As compared with the model group, in the Astr group, the mortality and CVF were significantly lower (53.3% vs. 23.3%, chi2 = 4.23, P < 0.05), and (17.4 +/- 1.2% vs. 8.6 +/- 0.9%, chi2 = 5.38, P < 0.05), respectively. As compared with the control group, Western blot analysis showed that expression of TGF-beta1 was decreased, MMP-1 and TIMP-1 were down-regulated, while expressions of MMP-13 and MMP-14 were up-regulated after Astr treatment.</p><p><b>CONCLUSION</b>Astr could lower the mortality and alleviate the myocardial fibrosis of mice with chronic myocarditis. Its antifibrotic effect might be realized by way of inhibiting TGF-beta1 expression and up-regulating the expressions of MMP-13 and MMP-14 in the heart tissues.</p>

Microarray analysis of extracellular matrix genes expression in myocardium of mouse with Coxsackie virus B3 myocarditis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Extracellular matrix (ECM) orchestrates cell behaviour including growth, death, apoptosis, adhesion, migration, and invasion by activating several signalling pathways. Certain components of ECM, such as integrins, may act as receptors or co-receptors of enterovirus. ECM-activated gene expressions in myocardium of viral heart disease including myocarditis and partial cardiomyopathy remain elusive. This study was to investigate the expression of ECM-activated genes in myocardium of mouse with viral myocarditis.</p><p><b>METHODS</b>BALB/c mice were infected with Coxsackie virus B3 (CVB3) to establish an animal model of myocarditis. Uninfected mice were also prepared and served as controls. Specific mRNA expression pattern in myocarditic mouse heart was analysed by an in-house cDNA microarray containing 8,192 genes. Overexpressed ECM genes were selected and subsequently confirmed by Northern blot analysis.</p><p><b>RESULTS</b>Nine ECM genes were isolated, from the array of 8,192 genes, as overexpressed genes in hearts of myocarditic mice in comparison with controls. Subsequent Northern blot analysis confirmed that four of the nine genes were highly expressed. Expression of these four genes, Fin15, ILk, Lamr1 and ADAMTS-1, has not been reported previously to be induced by Coxsackie virus.</p><p><b>CONCLUSION</b>CVB3-induced myocarditis is associated with gene expression profiles of certain ECM components.</p>