High Serum Level of Neopterin is a Risk Factor of Patients with Heart Failure

Serum neopterin concentration was measured in 198 patients with chronic heart failure (CHF) and 62 control subjects by ELISA. Patients were prospectively followed during a median follow-up period of 745 days with end points of cardiac death or re-hospitalization due to progressive heart failure. Serum concentration of neopterin increased with advancing New York Heart Association (NYHA) functional class (P < 0.001). High neopterin group had a significantly higher incidence of cardiac events than low neopterin group (P < 0.0001). In the multivariate Cox analysis, serum neopterin concentration was an independent risk factor for cardiac events (hazard ratio 1.70, 95%CI 1.16-2.50, P = 0.0068). Serum neopterin concentration is a novel prognostic marker for CHF

Increase in PTX3 expression after TAC operation and H₂O₂ stimulation.

<p>A. Time course of PTX3 expression in heart tissue after TAC. B. Immunohistochemistry of heart samples after TAC operation using anti PTX3 antibody. (top; ×200, bottom; ×400) C. PTX3 expression after H₂O₂ stimulation using neonatal rat cardiac myocytes and cardiac fibroblasts (left panel; cardiac myocytes, right panel; cardiac fibroblasts).</p

Gravimetric and echocardiographic data of PTX3-KO mice after TAC.

<p>WT, Wild type; PTX3-KO, PTX3 systemic knockout mice; TAC, thoracic aortic constriction; BW, body weight; HW, heart weight; LW, lung wet weight; IVS, interventricular septal wall thickness; LVEDD, left ventricular end-diastolic diameter; LVFS, left ventricular fractional shortening. All data are shown as mean ± SD (n = 10 per group).</p>*<p><i>P</i><0.05 and</p>**<p><i>P</i><0.01 vs. sham-operated mice of the same strain;</p>#<p><i>P</i><0.05 and</p>##<p><i>P</i><0.01 vs. TAC-operated WT mice at each time point, respectively.</p

Hypertrophic changes after TAC operation.

<p>A. Plasma concentrations of IL-6 at 5 days after TAC or sham operation in PTX3-KO mice (left) and PTX3-TG mice (right). B. IL-6 expression after TAC detected by quantitative PCR in PTX3-KO mice (left) and PTX3-TG mice (right). C. Representative photographs of hearts at 4 weeks after TAC and sham operation in PTX3-KO mice (left) and PTX3-TG mice (right). *<i>P</i><0.01 vs. sham mice of the same strain. Results are expressed as mean ± SD (n = 6–8).</p

Quantitative analysis of profibrotic and fetal type genes expression by real-time PCR in PTX3-KO (left) and in PTX3-TG (right) at 2 weeks after TAC or sham operation (n = 8).

<p>A, CTGF; B, collagen type I; C, collagen type III; D, β- MHC to α-MHC ratio; and E, ANF. Each expression levels was normalized to the GAPDH levels and expressed as fold increase over the levels in the respective WT sham-operated mice. *<i>P</i><0.01 vs. expression in sham mice of the same strain. Results are expressed as mean ± SD.</p

Phosphorylations of MAP kinase and nuclear transcriptional factor, NF-κB after TAC operation.

<p>A. Increase in phosphorylations of MAPK and NF-κB after TAC operation in PTX3-KO mice (left panel) and in PTX3-TG mice (right panel). B. Modulation of ERK1/2 and NF-κB p65 phosphorylation in PTX3-KO (left), PTX3-TG (right), compared with WT mice. C. ERK1/2 phosphorylation after recombinant PTX3 stimulation (left panel; cardiac myocytes, right panel; cardiac fibroblasts). *P<0.01 vs. sham-operated mice of the same strain. Results are expressed as mean ± SD (n = 8).</p

Hypertrophic and fibrotic changes after TAC operation.

<p>A. Representative histological micrographs of hematoxylin-eosin-stained and quantitative analysis of the cross-sectional areas of cardiomyocytes. B. Masson's trichrome-stained sections of the left ventricular myocardium in PTX3-KO mice strain (left) and in PTX3-TG mice strain (right) at 2 weeks after TAC or sham operation. C. Quantitative analysis of the fibrosis fractions at 2 weeks after TAC or sham operation, respectively (n = 8). *<i>P</i><0.01 vs. levels in sham-operated mice of the same strain. Results are expressed as mean ± SD (n = 8).</p

Gravimetric and echocardiographic data of PTX3-TG mice after TAC.

<p>Abbreviations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053133#pone-0053133-t001" target="_blank">Table 1</a>. PTX3-TG, PTX3 cardiac-specific overexpression mice. All data are shown as mean ± SD (n = 10 per group,).</p>*<p><i>P</i><0.05 and</p>**<p><i>P</i><0.01 vs. sham mice of the same strain;</p>#<p><i>P</i><0.05 and</p>##<p><i>P</i><0.01 vs. TAC-operated WT mice at each time point, respectively.</p