Woliang Yuan

CRP regulates the expression and activity of tissue factor as well as tissue factor pathway inhibitor via NF‐κB and ERK 1/2 MAPK pathway

It was found that C‐reactive protein (CRP) could significantly increase the expression and activity of tissue factor (TF), but decrease that of tissue factor pathway inhibitor (TFPI) in human umbilical vein endothelial cells (HUVECs) in dose‐ and time‐dependent manners, which could be antagonized by PDTC and U0126. CRP could also increase protein expression of phosphorylated nuclear factor‐kappaB (NF‐κB), IκB‐α and ERK1/2 in dose‐ and time‐dependent manner. In addition, neutralizing antibody to CD32 (FcgammaR II) could significantly attenuate the expression and activity of TF and TFPI induced by CRP. These results suggest that CRP may promote coagulation by enhancing the expression and activity of TF and reducing that of TFPI by activating NF‐κB and extracellular signal‐regulated kinase via FcgammaR II.

Clinical effectiveness of telemedicine for chronic heart failure: a systematic review and meta-analysis

Telemedicine interventions may be associated with reductions in hospital admission rate and mortality in patients with heart failure (HF). The present study is an updated analysis (as of June 30, 2016) of randomized controlled trials, where patients with HF underwent telemedicine care or the usual standard care. Data were extracted from 39 eligible studies for all-cause and HF-related hospital admission rate, length of stay, and mortality. The overall all-cause mortality (pooled OR=0.80, 95% CI 0.71 to 0.91, p<0.001), HF-related admission rate (pooled OR=0.63, 95% CI 0.53 to 0.76, p<0.001), and HF-related length of stay (pooled standardized difference in means=−0.37, 95% CI −0.72 to −0.02, p=0.041) were significantly lower in the telemedicine group (teletransmission and telephone-supported care), as compared with the control group. In subgroup analysis, all-cause mortality (pooled OR=0.69, 95% CI 0.56 to 0.86, p=0.001), HF-related admission rate (OR=0.61, 95% CI 0.42 to 0.88, p=0.008), HF-related length of stay (pooled standardized difference in means=−0.96, 95% CI −1.88 to −0.05, p=0.039) and HF-related mortality (OR=0.68, 95% CI 0.54 to 0.85, p=0.001) were significantly lower in the teletransmission group, as opposed to the standard care group, whereas only HF-related admission rate (OR=0.64, 95% CI 0.52 to 0.79, p<0.001) was lower in the telephone-supported care group. Overall, telemedicine was shown to be beneficial, with home-based teletransmission effectively reducing all-cause mortality and HF-related hospital admission, length of stay and mortality in patients with HF.

Dyssynchronous Pacing Triggers Endothelial-Mesenchymal Transition Through Heterogeneity of Mechanical Stretch in a Canine Model

BACKGROUND Endothelial-mesenchymal transition (EndMT) plays a pivotal role in cardiac fibrosis. However, it is unclear whether EndMT is involved in dyssynchronous heart failure (DHF). METHODS AND RESULTS Twelve dogs received 3-week rapid right ventricular pacing (RVP) to develop DHF and then were randomly divided into a RVP group (n=6; RVP for another 3 weeks) and a biventricular pacing (BiVP) group (n=6; BiVP for 3 weeks), and another 6 dogs were in the control group. Contractile function in BiVP group was a little better than that in RVP group (P<0.05), but significant heart failure remained in 2 groups. RVP induced more significant cardiac fibrosis and higher collagen 1A2 expression in the left ventricular lateral wall (late-contracting and high-stress) than that in the anterior wall, and for those in the BiVP group, it was much lower. CD31, S100A4, α-smooth muscle actin and collagen 1A2 were used to evaluate EndMT. EndMT levels, transforming growth factor-β (TGF-β)/snail signaling, collagen 1A2 and integrin β1 expression were much higher in the endothelial cells from the RVP lateral wall than that from BiVP. In this in vitro study, cyclic stretch could independently induce EndMT and enhance the pro-EndMT effect of TGF-β in HUVECs, which could be partly blocked by integrin β1 siRNA. CONCLUSIONS RVP-induced DHF could aggravate fibrosis due to regional heterogeneity of mechanical stress, and it was better in the BiVP group where mechanical stress-induced EndMT might play a pivotal role through the integrin β1 pathway.

Transcription factor decoys for activator protein-1 (AP-1) inhibit oxidative stress-induced proliferation and matrix metalloproteinases in rat cardiac fibroblasts

Activator protein-1 (AP-1), which is a transcription factor, is implicated in the transcriptional regulation of a wide range of genes that participate in cell proliferation and extracellular matrix production. This investigation was performed to test the hypothesis that transfection of cardiac fibroblasts (CFs) with sufficient amounts of decoy oligodeoxynucleotides (ODNs) containing the AP-1-binding site would result in binding to the transfactor AP-1, which would thereby prevent CF proliferation and matrix metalloproteinase (MMP) expression. CFs from Sprague-Dawley rat hearts were cultured and exposed to different concentrations of xanthine + xanthine oxidase (XXO) and AP-1 decoy ODNs. MMP expression was assayed after oxidative stress and transfection with AP-1 decoy ODNs by real-time quantitative polymerase chain reaction and Western blot. Cell growth was determined by the cell count. XXO significantly increased the DNA-binding activity of AP-1 in a dose-dependent manner. We found that transfection with AP-1 decoy ODNs strongly inhibited XXO-induced CF proliferation and MMP gene expression in vitro. Taken together, our data demonstrate that AP-1 is a key transcription factor that mediates CF proliferation and MMP synthesis under oxidative stress. Transfection with AP-1 decoy ODNs may be a novel strategy to inhibit CF proliferation and MMP synthesis.

Disruption of calcium homeostasis by cardiac-specific over-expression of PPAR-γ in mice: A role in ventricular arrhythmia.

AIMS Adverse cardiovascular effects induced by peroxisome proliferator activator receptor-γ (PPAR-γ) activation were observed in clinical setting. But the underlying mechanism is unclear. Now, transgenic mice with cardiac specific peroxisome proliferator activator receptor-γ overexpression (TG-PPAR-γ) were used to explore the possible mechanisms. MATERIALS AND METHODS Cardiac tissues from TG-PPAR-γ mice, a PPAR-γ over-expressing human cardiomyocyte line AC16 cell, and PPAR-γ agonist-treated primary cardiomyocytes were used to evaluate the expression of cardiac calcium regulatory proteins as sarcoplasmic reticulum Ca2+ ATPase, Na+/Ca2+ exchanger 1, ryanodine receptor 2 and phospholamban. Intracellular Ca2+ levels were also examined by flow cytometry and confocal microscopy with Fluo-4/AM in these cells. KEY FINDINGS In this study, frequent ventricular premature contraction and polymorphic ventricular tachycardia were observed in TG-PPAR-γ but not in wild-type mice. Besides, we found the calcium regulatory proteins expression were higher in the TG-PPAR-γ mice, PPAR-γ overexpressing human cardiomyocyte line AC16 cell and PPAR-γ agonist-treated primary cardiomyocytes than the control group respectively. In addition, an increase of intracellular calcium levels and CaMKII δ expression in PPAR-γ overexpression and PPAR-γ activation group. Moreover, Inhibition of CaMKII δ could improve the intracellular calcium levels and reduce the occurrence of ventricular arrhythmia. SIGNIFICANCE PPAR-γ over-expression perturbs the intracellular calcium homeostasis in cardiomyocytes which contribute to the ventricular arrhythmias and cardiac sudden death in TG-PPAR-γ mice.

Selective estrogen receptor modulators promising for cardiac syndrome X.

Cardiac syndrome X (CSX) is defined as a typical anginal-like chest pain with a transient ischemic electrocardiogram, but without abnormal coronary angiography. It is usually accepted that endothelial dysfunction, inflammation, oxidative stress and estrogen deficiency are the main reasons of CSX. There are some methods to treat CSX including statins, b blocker, angiotensin converting enzyme inhibitors, nitrates, estrogen, and so on. The estrogen replacement therapy (ERT), in particular, has been reported by many researchers to significantly reduce the frequency of chest pain after administration of estrogen, which has been explained as estrogen acting on its receptor to improve the endothelial function. However, it has been suggested that ERT must not be used for coronary heart disease due to its adverse effects. However, some selective estrogen receptor modulators (SERMs) can inhibit inflammatory response as well as oxidative stress, and improve the endothelial function, to reduce the occurrence of chest pain. Here, we hypothesize that SERMs may be the beneficial selection for patients with CSX.

Yes-associated protein mediates angiotensin II-induced vascular smooth muscle cell phenotypic modulation and hypertensive vascular remodelling

Yes‐associated protein (YAP) has been reported to regulate cell proliferation and differentiation. We aimed to characterize the role of YAP in angiotensin II (Ang II)‐induced hypertensive vascular remodelling (HVR) and vascular smooth muscle cells (VSMCs) phenotypic modulation and to explore the underlying mechanisms.

A Low-Normal Free Triiodothyronine Level Is Associated with Adverse Prognosis in Euthyroid Patients with Heart Failure Receiving Cardiac Resynchronization Therapy

Thyroid dysfunction is prevalent in patients with heart failure (HF) and hypothyroidism is related to the adverse prognosis of HF subjects receiving cardiac resynchronization therapy (CRT). We aim to investigate whether low-normal free triiodothyronine (fT3) level is related to CRT response and the prognosis of euthyroid patients with HF after CRT implantation.One hundred and thirteen euthyroid patients who received CRT therapy without previous thyroid disease and any treatment affecting thyroid hormones were enrolled. All of patients were evaluated for cardiac function and thyroid hormones (serum levels of fT3, free thyroxine [fT4] and thyroid-stimulating hormone [TSH]). The end points were overall mortality and hospitalization for HF worsening. During a follow-up period of 39 ± 3 weeks, 36 patients (31.9%) died and 45 patients (39.8%) had hospitalization for HF exacerbation. A higher rate of NYHA III/IV class and a lower fT3 level were both observed in death group and HF event group. Multivariate Cox regression analyses disclosed that a lower-normal fT3 level (HR = 0.648, P = 0.009) and CRT response (HR = 0.441, P = 0.001) were both independent predictors of overall mortality. In addition, they were also both related to HF re-hospitalization event (P < 0.01 for both). Patients with fT3 < 3.00 pmol/L had a significantly higher overall mortality than those with fT3 ≥ 3.00 pmol/L (P = 0.027). Meanwhile, a higher HF hospitalization event rate was also found in patients with fT3 < 3.00 pmol/L (P < 0.001).A lower-normal fT3 level is correlated with a worse cardiac function an adverse prognosis in euthyroid patients with HF after CRT implantation.