Decreased Spp1 Expression in Acute Myocardial Infarction after Ischemia and Reperfusion Injury.

BACKGROUND: With the progress of shock therapy and the establishment and promotion of methods such as thrombolytic therapy and percutaneous coronary intervention (PCI), many tissues and organs have been reperfused after ischemia which may cause even worse disorder called ischemia-reperfusion injury (IRI). mRNAs have been found to have significant impacts on ischemia-reperfusion through various mechanisms. In view of the accessibility of mRNAs from blood, we aimed to find the association between mRNA and ischemia-reperfusion. METHODS: We used the GSE83472 dataset from the Gene Expression Omnibus (GEO) database to find differential RNA expression between ischemia-reperfusion tissue and control samples. In addition, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to find the biological property of 449 RNAs from GSE83472 via the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Besides, Gene Set Enrichment Analysis (GSEA), a tool to find the pathway orientation of a gene set, was used for further study in the four most significant KEGG pathways. Furthermore, we constructed a protein-protein interaction (PPI) network. In the end, we used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting to measure and compare the expression of Spp1 in patients who accepted percutaneous coronary intervention. RESULTS: The bioinformatics analyses suggested that Spp1 was a hub gene in reperfusion after ischemia. The qRT-PCR result showed that the Spp1 expression was significantly downregulated in ischemia-reperfusion cells after PCI compared with normal samples and so as the western blotting. CONCLUSION: Spp1 might play an essential role in acute myocardial infarction after ischemia and reperfusion injury.

BTK Promotes Atherosclerosis by Regulating Oxidative Stress, Mitochondrial Injury, and ER Stress of Macrophages.

Atherosclerosis (AS) is a chronic metabolic disease in arterial walls, characterized by lipid deposition and persistent aseptic inflammation. AS is regarded as the basis of a variety of cardiovascular and cerebrovascular diseases. It is widely acknowledged that macrophages would become foam cells after internalizing lipoprotein particles, which is an initial factor in atherogenesis. Here, we showed the influences of Bruton's tyrosine kinase (BTK) in macrophage-mediated AS and how BTK regulates the inflammatory responses of macrophages in AS. Our bioinformatic results suggested that BTK was a potential hub gene, which is closely related to oxidative stress, ER stress, and inflammation in macrophage-induced AS. Moreover, we found that BTK knockdown could restrain ox-LDL-induced NK-κB signaling activation in macrophages and repressed M1 polarization. The mechanistic studies revealed that oxidative stress, mitochondrial injury, and ER stress in macrophages were also suppressed by BTK knockdown. Furthermore, we found that sh-BTK adenovirus injection could alleviate the severity of AS in ApoE-/- mice induced by a high-fat diet in vivo. Our study suggested that BTK promoted ox-LDL-induced ER stress, oxidative stress, and inflammatory responses in macrophages, and it may be a potential therapeutic target in AS.

Effect of C reactive protein on the sodium-calcium exchanger 1 in cardiomyocytes.

Numerous previous studies have found that C-reactive protein (CRP) is associated with cardiac arrhythmia and cardiac remodeling. However, the underlying mechanisms of this association remain unclear. Sodium-calcium exchanger 1 (NCX1) serves an important role in the regulation of intracellular calcium concentration, which is closely related with cardiac arrhythmia and cardiac remodeling. The present study aimed to evaluate the effects of CRP on NCX1 and intracellular calcium concentration in cardiomyocytes. Primary neonatal mouse ventricular cardiomyocytes were cultured and treated with varying concentrations of CRP (0, 5, 10, 20 and 40 µg/ml). The cardiomyocytes were also treated with NF-κB-specific inhibitor PTDC and a specific inhibitor of the reverse NCX1 KB-R7943 before their intracellular calcium concentrations were measured. mRNA and protein expression levels of NCX1 were detected by reverse transcription-quantitative PCR and western blotting, respectively and intracellular calcium concentration was evaluated by flow cytometry. CRP treatment significantly increased mRNA and protein expression levels of NCX1 in myocytes (P=0.024), as well as intracellular calcium concentration (P=0.01). These results were significantly attenuated by the NF-κB-specific inhibitor PDTC and a specific inhibitor of the reverse NCX1, KB-R7943. CRP significantly upregulated NCX1 expression and increased intracellular calcium concentration in cardiomyocytes via the NF-κB pathway, suggesting that CRP may serve a pro-arrhythmia role via direct influence on the calcium homeostasis of cardiomyocytes.

Long non-coding RNA Linc00092 inhibits cardiac fibroblast activation by altering glycolysis in an ERK-dependent manner.

AIMS: Cardiac fibroblast (CF) activation is the key event for cardiac fibrosis. The role of glycolysis and the glycolysis-related lncRNAs in CF activation are unknown. Thus, we aimed to investigate the role of glycolysis in CF activation and to identify the glycolysis-related lncRNAs involved. MAIN METHODS: Glycolysis-related lncRNAs were searched and their expression profiles were validated in activated human CF (HCF) and human failing heart tissues. Expression of the target lncRNA was manipulated to determine its effects on HCF activation and glycolysis. The underlying mechanisms of lncRNA-dependent glycolysis regulation were also addressed. KEY FINDINGS: HCF activation induced by transforming growth factor-ß1 was accompanied by an enhanced glycolysis, and 2-Deoxy-d-glucose, a specific glycolysis inhibitor, dramatically attenuated HCF activation. Twenty-eight glycolysis-related lncRNAs were identified and Linc00092 expression was changed mostly upon HCF activation. In human heart tissue, Linc00092 is primarily expressed in cardiac fibroblasts. Linc00092 knockdown activated HCFs with enhanced glycolysis, while its overexpression rescued the activated phenotype of HCFs and down-regulated glycolysis. Restoration of glycolysis abolished the anti-fibrotic effects conferred by Linc00092. Linc00092 inhibited ERK activation in activated HCFs, and ERK inhibition counteracted the fibrotic phenotype in Linc00092 knockdown HCFs. SIGNIFICANCE: These results revealed that Linc00092 could attenuate HCF activation by suppressing glycolysis. The inhibition of ERK by Linc00092 may play an important role in this process. Together, this provides a better understanding of the mechanism of CF activation and may serve as a novel target for cardiac fibrosis treatment.

Comparison of renal impairment post-myocardial infarction with reduced and preserved left ventricular function in rats with normal renal function.

This study aimed to compare the renal impairments in post-myocardial infarction (MI) rats with normal renal biochemical parameters at baseline with versus without cardiac dysfunction and explore the potential mechanisms involved in these differences. Sprague-Dawley rats with permanent ligation of coronary artery were used as MI models. Renal function, histological and molecular changes were compared between the reduced ejection fraction (EF) (EF < 40%) group and the preserved EF (EF ≥ 40%) group 3 or 9 weeks post-MI. The results revealed that blood cystatin C increased significantly at 9 but not 3 weeks, but it was not associated with cardiac dysfunction. Renal fibrosis and inflammatory cell infiltrations increased significantly in the reduced EF group than in the preserved EF group at 3 and 9 weeks. Glomerular podocyte injury, identified by increased immunostaining for desmin and decreased immunostaining for Wilms' tumor-1, was more significant in the reduced EF group than in the preserved EF group at 9, but not 3 weeks. The number of p16ink4a-positive and 8-hydroxy-2'-deoxyguanosine-positive podocytes was greater in the reduced EF group than in the preserved EF group at both time points. These changes were associated with increased expression of angiotensin II type 1/2 receptors at both time points. In conclusion, our study demonstrated that cardiac dysfunction accounted for substantially severity in renal parenchymal impairment in a partially time-dependent manner, and local activation of angiotensin II receptors, increased cell senescence and oxidative stress, and enhanced inflammatory reaction may be potential modulators participated in the deterioration of renal parenchymal injury.

Mesenchymal stem cell-derived exosomes ameliorate cardiomyocyte apoptosis in hypoxic conditions through microRNA144 by targeting the PTEN/AKT pathway.

BACKGROUND: A growing body of evidence suggests that stem cell-derived exosomal microRNAs (miRNAs) could be a promising cardioprotective therapy in the context of hypoxic conditions. The present study aims to explore how miRNA-144 (miR-144), a miRNA contained in bone marrow mesenchymal stem cell (MSC)-derived exosomes, exerts a cardioprotective effect on cardiomyocyte apoptosis in the context of hypoxic conditions and identify the underlying mechanisms. METHODS: MSCs were cultured using the whole bone marrow adherent method. MSC-derived exosomes were isolated using the total exosome isolation reagent and confirmed by nanoparticle trafficking analysis as well as western blotting using TSG101 and CD63 as markers. The hypoxic growth conditions for the H9C2 cells were established using the AnaeroPack method. Treatment conditions tested included H9C2 cells pre-incubated with exosomes, transfected with miR-144 mimics or inhibitor, or treated with the PTEN inhibitor SF1670, all under hypoxic growth conditions. Cell apoptosis was determined by flow cytometry using 7-ADD and Annexin V together. The expression levels of the miRNAs were detected by real-time PCR, and the expression levels of AKT/p-AKT, Bcl-2, caspase-3, HIF-1α, PTEN, and Rac-1 were measured by both real-time PCR and western blotting. RESULTS: Exosomes were readily internalized by H9C2 cells after co-incubation for 12 h. Exosome-mediated protection of H9C2 cells from apoptosis was accompanied by increasing levels of p-AKT. MiR-144 was found to be highly enriched in MSC-derived exosomes. Transfection of cells with a miR-144 inhibitor weakened exosome-mediated protection from apoptosis. Furthermore, treatment of cells grown in hypoxic conditions with miR-144 mimics resulted in decreased PTEN expression, increased p-AKT expression, and prevented H9C2 cell apoptosis, whereas treatment with a miR-144 inhibitor resulted in increased PTEN expression, decreased p-AKT expression, and enhanced H9C2 cell apoptosis in hypoxic conditions. We also validated that PTEN was a target of miR-144 by using luciferase reporter assay. Additionally, cells treated with SF1670, a PTEN-specific inhibitor, resulted in increased p-AKT expression and decreased H9C2 cell apoptosis. CONCLUSIONS: These findings demonstrate that MSC-derived exosomes inhibit cell apoptotic injury in hypoxic conditions by delivering miR-144 to cells, where it targets the PTEN/AKT pathway. MSC-derived exosomes could be a promising therapeutic vehicle to facilitate delivery of miRNA therapies to ameliorate ischemic conditions.

Construction and Analysis of a ceRNA Network in Cardiac Fibroblast During Fibrosis Based on in vivo and in vitro Data.

AIMS: Activation of cardiac fibroblasts (CF) is crucial to cardiac fibrosis. We constructed a cardiac fibroblast-related competing endogenous RNA (ceRNA) network. Potential functions related to fibrosis of "hub genes" in this ceRNA network were explored. MATERIALS AND METHODS: The Gene Expression Omnibus database was searched for eligible datasets. Differentially expressed messenger (m)RNA (DE-mRNA) and long non-coding (lnc)RNA (DE-lncRNA) were identified. microRNA was predicted and validated. A predicted ceRNA network was constructed and visualized by Cytoscape, and ceRNA crosstalk was validated. A Single Gene Set Enrichment Analysis (SGSEA) was done, and the Comparative Toxicogenomics Database (CTD) was employed to analyze the most closely associated pathways and diseases of DE-mRNA in the ceRNA network. The functions of DE-mRNA and DE-lncRNA in the ceRNA network were validated by small interfering (si)RNA depletion. RESULTS: The GSE97358 and GSE116250 datasets (which described differentially expressed genes in human cardiac fibroblasts and failing ventricles, respectively) were used for analyses. Four-hundred-and-twenty DE-mRNA and 39 DE-lncRNA, and 369 DE-mRNA and 93 DE-lncRNA were identified, respectively, in the GSE97358 and GSE116250 datasets. Most of the genes were related to signal transduction, cytokine activity, and cell proliferation. Thirteen DE-mRNA with the same expression tendency were overlapped in the two datasets. Twenty-three candidate microRNAs were predicted and the expression of 11 were different. Only two DE-lncRNA were paired to any one of 11 microRNA. Finally, two mRNA [ADAM metallopeptidase domain 19, (ADAM19) and transforming growth factor beta induced, (TGFBI)], three microRNA (miR-9-5p, miR-124-3p, and miR-153-3p) and two lncRNA (LINC00511 and SNHG15) constituted our ceRNA network. siRNA against LINC00511 increased miR-124-3p and miR-9-5p expression, and decreased ADAM19 and TGFBI expression, whereas siRNA against SNHG15 increased miR-153-3p and decreased ADAM19 expression. ADAM19 and TGFBI were closely related to the TGF-ß1 pathway and cardiac fibrosis, as shown by SGSEA and CTD, respectively. Depletion of two mRNA or two lncRNA could alleviate CF activation. CONCLUSIONS: The CF-specific ceRNA network, including two lncRNA, three miRNA, and two mRNA, played a crucial role during cardiac fibrosis, which provided potential target genes in this field.

Angiotensin II receptor blocker reverses heart failure by attenuating local oxidative stress and preserving resident stem cells in rats with myocardial infarction.

The present study aimed to test whether angiotensin receptor blockers (ARBs) are cardioprotective after myocardial infarction (MI) by preventing augmented local renin-angiotensin-system (RAS)-induced oxidative stress injury and senescence, preserving resident stem cells, and restoring the insulin-like growth factor (IGF-1)/IGF-1 receptor (IGF-R) pathway. Sprague-Dawley rats with ligated or unligated coronary arteries were treated with losartan (20 mg/kg/d) or vehicle for 3 or 9 weeks. Heart function and molecular and histological changes were assessed. It was found MI induced left ventricular dysfunction and remodeling, increased levels of the oxidative stress marker 8-hydroxy-2'-deoxyguanosine and cell senescence marker p16ink4a, and downregulated the IGF-1/IGF-1R/Akt pathway after both 3 and 9 weeks post-MI. MI induced an increase in stem cells identified by immunostaining for c-kit and Wilms' tumor-1 predominantly after 3 weeks. Losartan significantly inhibited local cardiac RAS activation and improved left ventricular function and remodeling at both timepoints. Losartan also preserved c-kit- and Wilms' tumor-1-positive cells (particularly at 3 weeks), attenuated 8-hydroxy-2'-deoxyguanosine- and p16ink4a-positive cardiomyocytes, and restored the IGF-1/IGF-1R/Akt pathway at both 3 and 9 weeks. In conclusion, ARBs aided cardiac repair post-MI through short-term preservation of stem cells and persistent anti-oxidative stress and anti-senescence effects, partially by attenuating activation of cardiac RAS and restoring the local IGF-1/IGF-1R/Akt pathway.

Angiotensin II receptor blocker attenuates intrarenal renin-angiotensin-system and podocyte injury in rats with myocardial infarction.

The mechanisms and mediators underlying common renal impairment after myocardial infarction (MI) are still poorly understood. The present study aimed to test the hypothesis that angiotensin II type 1 receptor blockers (ARBs) provides renoprotective effects after MI by preventing augmented intrarenal renin-angiotensin-system (RAS)-induced podocyte injury. Sprague-Dawley rats that underwent ligation of their coronary arteries were treated with losartan (20 mg/kg/d) or vehicle for 3 or 9 weeks. Renal function, histology and molecular changes were assessed. The current study revealed that MI-induced glomerular podocyte injury was identified by increased immunostaining for desmin and p16(ink4a), decreased immunostaining for Wilms' tumor-1 and podocin mRNA expression, and an induced increase of blood cystatin C at both 3 and 9 weeks. These changes were associated with increased intrarenal angiotensin II levels and enhanced expressions of angiotensinogen mRNA and angiotensin II receptor mRNA and protein. These changes were also associated with decreased levels of insulin-like growth factor (IGF-1) and decreased expressions of IGF-1 receptor (IGF-1R) protein and mRNA and phosphorylated(p)-Akt protein at 9 weeks, as well as increased expressions of 8-hydroxy-2'-deoxyguanosine at both time points. Treatment with losartan significantly attenuated desmin- and p16(ink4a)-positive podocytes, restored podocin mRNA expression, and decreased blood cystatin C levels. Losartan also prevented RAS activation and oxidative stress and restored the IGF-1/IGF-1R/Akt pathway. In conclusion, ARBs prevent the progression of renal impairment after MI via podocyte protection, partially by inhibiting the activation of the local RAS with subsequent enhanced oxidative stress and an inhibited IGF-1/IGF-1R/Akt pathway.

Protection of renal impairment by angiotensin II type 1 receptor blocker in rats with post-infarction heart failure.

Renal impairment is a frequent accompaniment post-myocardial infarction (MI) heart failure. However, the mechanisms and predictors are yet poorly understood. The present study aimed to explore early markers for renal impairment and to test the hypothesis that angiotensin II type 1 receptor (AT1R) blocker exerted renoprotection by regulating local angiotensin II receptors post-MI heart failure. Sprague-Dawley rats underwent ligation of the left descending coronary artery and were treated with losartan (20 mg/kg/day) or vehicle for 3 or 9 weeks. Samples of urine, blood, and kidney were collected for assessment of renal function, histology, and protein changes. The current study revealed that blood cystatin C, rather than serum creatinine and blood urea nitrogen, as well as urine proteins, increased post-MI heart failure significantly. These changes were associated with increased immunohistochemical staining of AT1R and AT2R proteins, accompanied by increased renal fibrosis, tubular necrosis, and inflammatory cell infiltration. Treatment with losartan for MI rats significantly attenuated upregulated AT1R but not AT2R. Losartan also decreased blood cystatin C levels and attenuated renal fibrosis, tubular necrosis, and inflammatory cell infiltration. In conclusion, blood cystatin C may be a better marker for early renal impairment. AT1R blockers modulated local angiotensin II receptors, as well as inflammatory reaction and profibrotic effects, providing potential clinical application in the setting of cardiorenal syndrome post-MI.

[Glycometabolic state in hypertensive and normotensive patients: identifying candidates for oral glucose tolerance tests].

OBJECTIVE: To characterize unknown glycometabolic state in patients with essential hypertension (EHT) and normotensive patients and determine which EHT patients are candidates for oral glucose tolerance tests (OGTTs). METHODS: This cross-sectional study consecutively recruited 895 EHT patients and 486 normotensive patients. The data including blood glucose, blood pressure, blood lipids, angiography profiles, and left ventricular parameters were collected. RESULTS: OGTTs performed in all patients revealed that the prevalence of abnormal glucose metabolism (AGM) was significantly higher in EHT patients than in normotensive patients at both baseline (P<0.001) and post-OGTT analysis (P<0.001). In total, 76.4% of the individuals with impaired glucose tolerance and 78.2% of individuals with newly diagnosed diabetes would have remained undetected if OGTTs had not been performed. Newly diagnosed AGM was significantly correlated with the presence and severity of coronary stenosis and left ventricular structure abnormalities and dysfunction. EHT patients with fasting glucose ≥5.6 mmol/L, hypertension duration exceeding 10 years, coronary artery disease, high-sensitivity C-reactive protein >3 mg/L, or high levels of apoB/apoA-1 ratio were at high risk of AGM. CONCLUSIONS: AGM is more common in patients with EHT than in normotensive patients, and OGTTs is a cost-effective strategy to detect AGM in EHT patients.

Comparison of cardiac stem cells and mesenchymal stem cells transplantation on the cardiac electrophysiology in rats with myocardial infarction.

INTRODUCTION: Whether transplanted cardiac stem cells (CSCs) and mesenchymal stem cells (MSCs) improved ventricular fibrillation threshold (VFT) similarly is still unclear. We sought to compare the effects of the CSC and MSC transplantation on the electrophysiological characteristics and VFT in rats with myocardial infarction (MI). METHODS: MI was induced in 30 male Sprague-Dawley rats. Two weeks later, animals were randomized to receive 5 × 10(6) CSCs labeled with PKH26 in PBS or 5 × 10(6) MSCs labeled with PKH26 in phosphate buffer solution(PBS) or PBS alone injection into the infarcted anterior ventricular free wall. Six weeks after the injection, electrophysiological characteristics and VFT were measured. Labeled CSCs and MSCs were observed in 5 µm cryostat sections from each heart. RESULTS: Malignant ventricular arrhythmias were significantly (P = 0.0055) less inducible in the CSC group than the MSC group. The VFTs were improved in the CSC group compared with the MSC group. Labeled CSCs and MSCs were identified in the infarct zone and infarct marginal zone. Labeled CSCs expressed Connexin-43, von Willebrand factor, α-smooth muscle actin and α-sarcomeric actin,while the Labeled MSCs expressed von Willebrand factor, α-smooth muscle actin and α-sarcomeric actin in vivo. CONCLUSIONS: After 6 weeks of cell transplantation, CSCs are superior to MSCs in modulating the electrophysiological abnormality and improving the VFT in rats with MI. CSCs and MSCs express markers that suggest muscle, endothelium and vascular smooth muscle phenotypes in vivo, but MSCs rarely express Connexin-43.

Predictive value of first fasting plasma glucose compared with admission plasma glucose for undiagnosed diabetes in a stable cardiology population.

OBJECTIVES: The study compared the predictive value of admission plasma glucose (APG) and first fasting plasma glucose (FPG) in stratifying patients meriting an oral glucose tolerance test (OGTT). DESIGN AND METHODS: Characteristics of APG, FPG and OGTT 2-hour glucose as well as other blood measurements, physical examinations and medical information were assessed in 994 patients without known diabetes. RESULTS: The prevalences of diabetes and impaired glucose tolerance were 24.6% and 37.9%, according to an OGTT, respectively. The first FPG demonstrated stronger predictive value in diagnosing diabetes than APG did both in overall and in patients with less clinical value. Compared to the first FPG, APG provided less value to coronary artery disease, hypertension and high-sensitivity C-reactive protein for diabetes screening. CONCLUSIONS: The first FPG exerted more predictive value than APG did and was still a preferable reference prior to APG in stratifying patients for undiagnosed diabetes by an OGTT.

Local activation of cardiac stem cells for post-myocardial infarction cardiac repair.

The prognosis of patients with myocardial infarction (MI) and resultant chronic heart failure remains extremely poor despite continuous advancements in optimal medical therapy and interventional procedures. Animal experiments and clinical trials using adult stem cell therapy following MI have shown a global improvement of myocardial function. The emergence of stem cell transplantation approaches has recently represented promising alternatives to stimulate myocardial regeneration. Regarding their tissue-specific properties, cardiac stem cells (CSCs) residing within the heart have advantages over other stem cell types to be the best cell source for cell transplantation. However, time-consuming and costly procedures to expanse cells prior to cell transplantation and the reliability of cell culture and expansion may both be major obstacles in the clinical application of CSC-based transplantation therapy after MI. The recognition that the adult heart possesses endogenous CSCs that can regenerate cardiomyocytes and vascular cells has raised the unique therapeutic strategy to reconstitute dead myocardium via activating these cells post-MI. Several strategies, such as growth factors, mircoRNAs and drugs, may be implemented to potentiate endogenous CSCs to repair infarcted heart without cell transplantation. Most molecular and cellular mechanism involved in the process of CSC-based endogenous regeneration after MI is far from understanding. This article reviews current knowledge opening up the possibilities of cardiac repair through CSCs activation in situ in the setting of MI.

Bone marrow mesenchymal stem cells for post-myocardial infarction cardiac repair: microRNAs as novel regulators.

Transplantation of bone marrow-derived mesenchymal stem cells (MSCs) is safe and may improve cardiac function and structural remodelling in patients following myocardial infarction (MI). Cardiovascular cell differentiation and paracrine effects to promote endogenous cardiac regeneration, neovascularization, anti-inflammation, anti-apoptosis, anti-remodelling and cardiac contractility, may contribute to MSC-based cardiac repair following MI. However, current evidence indicates that the efficacy of MSC transplantation was unsatisfactory, due to the poor viability and massive death of the engrafted MSCs in the infarcted myocardium. MicroRNAs are short endogenous, conserved, non-coding RNAs and important regulators involved in numerous facets of cardiac pathophysiologic processes. There is an obvious involvement of microRNAs in almost every facet of putative repair mechanisms of MSC-based therapy in MI, such as stem cell differentiation, neovascularization, apoptosis, cardiac remodelling, cardiac contractility and arrhythmias, and others. It is proposed that therapeutic modulation of individual cardiovascular microRNA of MSCs, either mimicking or antagonizing microRNA actions, will hopefully enhance MSC therapeutic efficacy. In addition, MSCs may be manipulated to enhance functional microRNA expression or to inhibit aberrant microRNA levels in a paracrine manner. We hypothesize that microRNAs may be used as novel regulators in MSC-based therapy in MI and MSC transplantation by microRNA regulation may represent promising therapeutic strategy for MI patients in the future.

Combined use of high-sensitivity C-reactive protein and apolipoprotein B/apolipoprotein A-1 ratio prior to elective coronary angiography and oral glucose tolerance tests.

OBJECTIVES: The study aimed to investigate the predictive value of the combination of high-sensitivity C-reactive protein (hs-CRP) and apolipoprotein B (apoB)/apoA-1 ratio for the outcomes of coronary angiography (CAG), echocardiography and oral glucose tolerance tests (OGTTs). DESIGN AND METHODS: Hs-CRP, apoB, apoA-1, and the profiles of CAG, echocardiography and OGTTs as well as traditional risk factors were measured in 1757 cardiology patients. RESULTS: Hs-CRP or apoB/apoA-1 ratio was significantly correlated with the presence and severity of angiographic profiles, the levels of left ventricular (LV) ejection fraction, LV mass and LV mass index, and the presence of abnormal glucose metabolism. The combination of hs-CRP and apoB/apoA-1 ratio had greater correlation with abnormal glucose metabolism than its individual components in patients with normal fasting glucose, and was an independent predictor for coronary artery disease. CONCLUSIONS: The combination of hs-CRP and apoB/apoA-1 ratio may be a strong predictor for coronary artery disease and abnormal glucose metabolism.

H3K27me3 protein is a promising predictive biomarker of patients' survival and chemoradioresistance in human nasopharyngeal carcinoma.

Trimethylation of lysine 27 on histone H3 (H3K27me3) is an epigenetic change which plays a critical role in tumor development and/or progression. However, the molecular status of H3K27me3 and its clinicopathologic/prognostic significance in nasopharyngeal carcinoma (NPC) have not been elucidated. In this study, the methods of Western blotting and immunohistochemistry (IHC) were utilized to examine the expression of H3K27me3 protein in NPC tissues and nonneoplastic nasopharyngeal epithelial tissues. Receiver operating characteristic (ROC) curve analysis was used to determine the cutpoint for H3K27me3 high expression. High expression of H3K27me3 could be observed in 127/209 (60.8%) of NPCs and in 8/50 (16.0%) normal nasopharyngeal epithelial tissues (P < 0.001). Further correlation analysis demonstrated that high expression of H3K27me3 was positively associated with tumor later T classification, tumor metastasis, advanced clinical stage and chemoradioresistance (P < 0.05). Moreover, high expression of H3K27me3 was closely associated with NPC patient shortened survival time as evidenced by univariate and multivariate analysis (P < 0.05). Consequently, a new clinicopathologic prognostic model with three poor prognostic factors (H3K27me3 expression, distant metastasis and treatment regimen) was constructed. The model could stratify risk significantly (low, intermediate and high) for overall survival and progression-free survival (P < 0.0001). These findings provide evidence that H3K27me3 expression, as examined by IHC, has the potential to be used as an immunomarker to predict NPC chemoradiotherapy response and patient prognosis. The combined clinicopathologic prognostic model may become a useful tool for identifying NPC patients with different clinical outcomes.

Repair mechanisms of bone marrow mesenchymal stem cells in myocardial infarction.

The prognosis of patients with myocardial infarction (MI) and resultant chronic heart failure remains extremely poor despite advances in optimal medical therapy and interventional procedures. Animal experiments and clinical trials using adult stem cell therapy following MI have shown a global improvement of myocardial function. Bone marrow-derived mesenchymal stem cells (MSCs) hold promise for cardiac repair following MI, due to their multilineage, self-renewal and proliferation potential. In addition, MSCs can be easily isolated, expanded in culture, and have immunoprivileged properties to the host tissue. Experimental studies and clinical trials have revealed that MSCs not only differentiate into cardiomyocytes and vascular cells, but also secrete amounts of growth factors and cytokines which may mediate endogenous regeneration via activation of resident cardiac stem cells and other stem cells, as well as induce neovascularization, anti-inflammation, anti-apoptosis, anti-remodelling and cardiac contractility in a paracrine manner. It has also been postulated that the anti-arrhythmic and cardiac nerve sprouting potential of MSCs may contribute to their beneficial effects in cardiac repair. Most molecular and cellular mechanisms involved in the MSC-based therapy after MI are still unclear at present. This article reviews the potential repair mechanisms of MSCs in the setting of MI.

Glucometabolic state in Chinese patients undergoing elective coronary angiography.

AIM: The aim of this study is to characterize the glucometabolic state of patients undergoing elective coronary angiography (CA) in a subpopulation in China. METHODS AND RESULTS: This study recruited 896 patients undergoing elective CA for the evaluation of suspected coronary artery disease (CAD). Oral glucose tolerance tests (OGTTs) performed in patients without previously known diabetes revealed that 173 (19.2%) had newly diagnosed diabetes and 281 (31.5%) had impaired glucose regulation. The prevalence of abnormal glucose metabolism (AGM) was significant difference among three groups of CA diagnosis, including normal coronary, nonsignificant stenosis and CAD. Overall, the proportion of patients with type 2 diabetes increased from 22.0% at baseline to 41.2% post-OGTT analysis. In total, 270 (59.5%) patients with AGM would have remained undetected if OGTTs had not been performed. Patients with CAD, hypertension, dyslipidemia, obesity and high C-reactive protein levels were at high risk of AGM. CONCLUSIONS: AGM is common and underestimated by FPG testing alone in patients undergoing elective CA. OGTTs should be routinely performed to assess the glucometabolic state of patients undergoing elective CA, especially in patients with high risks of AGM. Detecting the state of AGM in CA individuals may provide strategies to reduce the progression of AGM and associated complications.