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Telmisartan is an angiotensin II receptor blocker that displays unique PPAR-γ modulating activity. PPAR-γ Agonists have been shown to decrease susceptibility to atrial fibrillation through their antioxidant and antiapoptotic effects. The aim of this study was to determine whether telmisartan would have a greater effect on susceptibility to atrial arrhythmia in a hypertensive rat model than valsartan, which is a traditional angiotensin II receptor blocker. In this study, spontaneously hypertensive rats were treated with 10 mg *[(kg body mass).sup.-1]*[d.sup.-1] telmisartan (TEL group), 10 mg-[(kg body mass).sup.-1]*[d.sup.-1] valsartan (VAL group), or vehicle (saline; SHR group) for 4 weeks. Age-matched Wistar-Kyoto rats (WKY) were used as normotensive controls. After 4 weeks of treatment, we performed echocardiographic assessment, electrophysiological analysis, histological evaluation, and Western blot analysis. Telmisartan decreased systolic blood pressure to a similar extent as valsartan. Relative to the WKY controls, atrial arrhythmia susceptibility was significantly increased in the SHR group, and was significantly decreased by both telmisartan and valsartan, albeit to a greater extent with telmisartan. Arrhythmogenic atrial remodeling, including enlargement of the left atrium, myocyte hypertrophy, interstitial fibrosis, and myocyte apoptosis, was observed in the SHR group, and was accompanied by activated RAS-ERK signaling and suppressed PI3K-Akt-eNOS signaling. The results suggest that telmisartan reduced susceptibility to atrial arrhythmia to a greater extent than valsartan, ameliorated atrial remodeling, and reversed imbalances in the RAS-ERK and PI3K-Akt-eNOS pathways. Key words: hypertension, atrial fibrillation, structural remodeling, angiotensin receptor blockers, signaling pathway. Le telmisartan est un antagoniste du recepteur de l'angiotensine II qui exerce une activite modulatrice PPAR-γ unique. Les agonistes du PPAR-γ se sont averes diminuer la susceptibilite a la fibrillation auriculaire grace a leurs proprietes antioxydantes et anti-apoptose. Le but de cette etude etait de determiner si le telmisartan exercerait un effet sur la susceptibilite a l'arythmie auriculaire superieur a celui du valsartan, un antagoniste du recepteur de l'angiotensine II traditionnel, dans un modele de rats hypertendus. Dans cette etude, des rats spontanement hypertendus (SHR) ont ete traites avec 10 mg x [(kg de masse corporelle).sup.-1] x [jour.sup.-1] de telmisartan (TEL), 10 mg-[(kg de masse corporelle).sup.-1] x [jour.sup.-1] de valsartan (VAL) ou le vehicule (saline) pendant 4 semaines. Des rats Wistar-Kyoto (WKY) appareilles suivant l'age ont ete utilises comme controles normotensifs. Apres 4 semaines de traitement, des evaluations par echocardiographie, des analyses par electrophysiologie, des evaluations histologiques et des buvardages Western ont ete realises. Le telmisartan diminuait la pression sanguine systolique au meme degre que le valsartan. Comparativement aux controles WKY, la susceptibilite a l'arythmie auriculaire etait significativement accrue chez les rats SHR et significativement diminuee par le telmisartan et la valsartan, quoique le telmisartan ait ete plus efficace (TEL vs VAL). Un remodelage auriculaire arythmogenique, incluant l'elargissement de l'oreillette gauche, l'hypertrophie des myocytes, la fibrose interstitielle et l'apoptose des myocytes, etait observe chez les animaux SHR et il etait accompagne d'une activation de la signalisation RAS-ERK et d'une suppression de la signalisation PI3K-Akt-eNOS. Ces resultats suggerent que le telmisartan a reduit la susceptibilite a l'arythmie auriculaire dans une plus large mesure que le valsartan, a ameliore le remodelage auriculaire et a renverse les debalancements entre les voies de signalisation RAS-ERK et PI3K-Akt-eNOS. [Traduit par la Redaction] Mots-cles : hypertension, fibrillation auriculaire, remodelage structural, antagonistes du recepteur de l'angiotensine, voie de signalisation., Introduction Atrial fibrillation (AF), an important risk factor for stroke and mortality, is the most prevalent arrhythmia diagnosed in clinical practice (Wilhelmsen et al. 2001). Hypertension is a strong and [...]

In recent years, the role of circular RNA in cancer cells has been studied broadly; however, the functional significance of circular RNA in the regulation of the tumor microenvironment (TME) is not fully understood. In this study, we aimed to reveal the role of circ_TNFRSF21 in M2 macrophage‐induced cutaneous squamous cell carcinoma (cSCC) angiogenesis. Quantitative polymerase chain reaction and Western blotting were performed to determine the levels of the indicated genes. Direct binding between circ_TNFRSF21 and miR‐3619‐5p, miR‐3619‐5p, and ROCK2 was verified by dual‐luciferase activity. The migration and invasion of human umbilical vein endothelial cells were evaluated by wound healing and transwell assays. Tube formation was performed to detect in vitro angiogenesis. Circ_TNFRSF21 and ROCK2 were upregulated in cSCC tissue, while miR‐3619‐5p was downregulated. Circ_TNFRSF21 negatively regulated the expression of miR‐3619‐5p, while miR‐3619‐5p negatively regulated the expression of ROCK2. miR‐3619‐5p suppressed tube formation by inhibiting ROCK signaling. M2 macrophages facilitated tube formation via the circ_TNFRSF21/miR‐3619‐5p/ROCK2 axis. Our present study revealed that circ_TNFRSF21 was elevated in M2 macrophages and mediated M2 macrophage‐induced tube formation in vitro. [ABSTRACT FROM AUTHOR]

The relationship between stent expansion conditions and clinical outcomes is not completely understood. This prospective cohort study included patients who were successfully implanted with second-generation drug-eluting stent in 2012 and received follow-up angiography in 9-12 months. Stent over-expansion was defined as ≥ 1.05 of the stented segment over the reference artery diameter. Imaging parameters were measured, and the follow-up period was 7 years. A total of 123 patients with 161 lesions were enrolled, and 75 (46.58%) stents were found to be over-expanded. The baseline clinical and procedural data were comparable. Stent over-expansion showed a markedly increased diameter stenosis percentage (DSP) at 1-year follow-up (24.12 ± 21.10% vs. 14.65 ± 16.75%, P = 0.002) and high late lumen loss (LLL) in-segment (0.54 ± 0.62 mm vs. 0.31 ± 0.55 mm, P = 0.014). Furthermore, 63 patients with ≥ 1 over-expanded stented lesions were classified into the over-expansion group. Cumulative major cardiac adverse event (MACE) was higher in the over-expansion group than the norm-expansion group (17.5% vs. 8.3%, P = 0.133). Target lesion revascularization/target vessel revascularization increased during the 7-year follow-up period in the over-expansion group compared with the norm-expansion group (11.1% vs. 3.3%, P = 0.098). The Kaplan-Meier cumulative MACE-free survival showed a better tendency for statistical differences in the norm-expansion group than in the over-expansion group (log-rank test; P = 0.083). Conclusion: Stent over-expansion is associated with a significant increase in LLL and DSP at 1-year angiographic follow-up and with the increasing trend of cumulative MACE during 7-year clinical follow-up period compared with stent norm-expansion. Stent over-expansion needs to be avoided. [ABSTRACT FROM AUTHOR]

Objectives The present study established criteria to differentiate simple from complex bifurcation lesions and compared 1-year outcomes stratified by lesion complexity after provisional stenting (PS) and 2-stent techniques using drug-eluting stents. Background Currently, no criterion can distinguish between simple and complex coronary bifurcation lesions. Comparisons of PS and 2-stent strategies stratified by lesion complexity have also not been reported previously. Methods Criteria of bifurcation complexity in 1,500 patients were externally tested in another 3,660 true bifurcation lesions after placement of drug-eluting stents. The primary endpoint was the occurrence of a major adverse cardiac event (MACE) at 12 months. The secondary endpoint was the rate of stent thrombosis (ST). Results Complex (n = 1,108) bifurcation lesions were associated with a higher 1-year rate of MACE (16.8%) compared with simple (n = 2,552) bifurcation lesions (8.9%) (p < 0.001). The in-hospital ST and 1-year target lesion revascularization rates after 2-stent techniques in the simple group (1.0% and 5.6%, respectively) were significantly different from those after PS (0.2% [p = 0.007] and 3.2% [p = 0.009], respectively); however, 1-year MACE rates were not significantly different between the 2 groups. For complex bifurcation lesions, 2-stent techniques had lower rates of 1-year cardiac death (2.8%) and in-hospital MACE (5.0%) compared with PS (5.3%, p = 0.047; 8.4%, p = 0.031). Conclusions Complex bifurcation lesions had higher rates of 1-year MACE and ST. The 2-stent and PS techniques were overall equivalent in 1-year MACE. However, 2-stent techniques for complex lesions elicited a lower rate of cardiac death and in-hospital MACE but higher rates of in-hospital ST and revascularization at 1 year for simple lesions. [ABSTRACT FROM AUTHOR]

Highlights: [•] BFGF exists only in the cytoplasm of live cells. [•] BFGF cannot be secreted into the extracellular space to promote cell growth. [•] We combine the secretion-promoting signal peptide of FGF4. [•] We successfully modified BMSCs with the fused genes of FGF4-bFGF. [•] We promoted the therapeutic effects of transplanted BMSCs in myocardial infarction. [Copyright &y& Elsevier]

Purpose: To evaluate the relationship between the serum calcitonin gene-related peptide (CGRP) level and severity of coronary stenosis.Methods: A total of 233 eligible patients who underwent coronary angiography were divided into two groups: a control and a coronary heart disease (CHD) group. The angiographic severity of coronary stenosis was evaluated by SYNTAX and Gensini scores. The incidence of major adverse cardiovascular events within two years was collected.Results: A negative correlation between serum CGRP levels and Gensini scores was observed in all patients (r=-0.352, p<0.001), the control group (r=-0.422, p<0.001) and the CHD group (r=-0.393, p<0.001). Serum CGRP levels were negatively associated with SYNTAX scores in the CHD group (r=-0.522, p<0.001). The area under the curve of CGRP for identifying high SYNTAX scores (>22) was 0.772 [95% confidence interval (CI): 0.673-0.870, p<0.001], and for identifying high Gensini scores was 0.744 (95% CI: 0.646-0.842, p<0.001). A CGRP concentration of 25.05 pg/ml was selected as the cutoff point. A low CGRP level (<25.05 pg/ml) was an independent predictor of severe coronary stenosis, a SYNTAX score >22 [odds ratio (OR) =5.819, 95% CI: 2.240-15.116; p<0.001] and a high Gensini score (>64) (OR=4.943, 95% CI: 2.020-12.095; p<0.001). The low CGRP group had a higher incidence of major adverse cardiovascular events within two years (11.1 vs. 3.1%, p=0.031).Conclusion: In coronary atherosclerosis patients without acute myocardial injury, serum CGRP levels were negatively associated with the severity of coronary stenosis. [ABSTRACT FROM AUTHOR]

Background. Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) may be a potential biomarker of coronary artery disease (CAD) and stroke. Objective. We aimed to investigate the association and prognostic value of elevated sLOX-1 concentrations with regard to long-term major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with CAD undergoing primary percutaneous coronary intervention (PCI). Methods. A total of 1011 patients were enrolled. Serum sLOX-1 concentrations were detected by the enzyme-linked immunosorbent assay (ELISA). Patients were followed for 2 years. Multivariate Cox regression and Kaplan-Meier survival curve were explored to assess the association between sLOX-1 and MACCEs. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of sLOX-1. Results. Two-year MACCEs were associated with serum sLOX-1 concentrations (HR 1.278, 95% CI 1.019-1.604, P=0.034), left main disease (HR 2.938, 95% CI 1.246-6.925, P=0.014), small-caliber stents used (HR 2.207, 95% CI 1.189-4.095, P=0.012), and total stent length (HR 1.057, 95% CI 1.005-1.112, P=0.030). Serum sLOX-1 concentration≥1.10 ng/ml had maximum sensitivity and specificity in predicting the occurrence of 2-year MACCEs (P<0.001). Patients with higher serum sLOX-1 concentrations showed a significantly higher incidence of MACCEs in the Kaplan-Meier curve (P<0.001). The combination of any of the risk factors identified in multiple Cox regression was associated with a stepwise increase in MACCE rate (P<0.001). Conclusions. High baseline serum sLOX-1 concentration predicts 2-year MACCEs and shows an additional prognostic value to conventional risk factors in patients after primary PCI. sLOX-1 determination might play a complementary role in the risk stratification of patients with CAD treated with PCI. [ABSTRACT FROM AUTHOR]