Mechanisms and therapeutic strategies of extracellular vesicles in cardiovascular diseases.

Cardiovascular disease (CVD) significantly impacts global society since it is the leading cause of death and disability worldwide, and extracellular vesicle (EV)-based therapies have been extensively investigated. EV delivery is involved in mediating the progression of CVDs and has great potential to be biomarker and therapeutic molecular carrier. Besides, EVs from stem cells and cardiac cells can effectively protect the heart from various pathologic conditions, and then serve as an alternative treatment for CVDs. Moreover, the research of using EVs as delivery carriers of therapeutic molecules, membrane engineering modification of EVs, or combining EVs with biomaterials further improves the application potential of EVs in clinical treatment. However, currently there are only a few articles summarizing the application of EVs in CVDs. This review provides an overview of the role of EVs in the pathogenesis and diagnosis of CVDs. It also focuses on how EVs promote the repair of myocardial injury and therapeutic methods of CVDs. In conclusion, it is of great significance to review the research on the application of EVs in the treatment of CVDs, which lays a foundation for further exploration of the role of EVs, and clarifies the prospect of EVs in the treatment of myocardial injury.

The role of major immune cells in myocardial infarction.

Myocardial infarction (MI) is a cardiovascular disease (CVD) with high morbidity and mortality worldwide, often leading to adverse cardiac remodeling and heart failure, which is a serious threat to human life and health. The immune system makes an important contribution to the maintenance of normal cardiac function. In the disease process of MI, necrotic cardiomyocytes release signals that activate nonspecific immunity and trigger the action of specific immunity. Complex immune cells play an important role in all stages of MI progression by removing necrotic cardiomyocytes and tissue and promoting the healing of damaged tissue cells. With the development of biomaterials, cardiac patches have become an emerging method of repairing MI, and the development of engineered cardiac patches through the construction of multiple animal models of MI can help treat MI. This review introduces immune cells involved in the development of MI, summarizes the commonly used animal models of MI and the newly developed cardiac patch, so as to provide scientific reference for the accurate diagnosis and effective treatment of MI.

IDO1 depletion induces an anti-inflammatory response in macrophages in mice with chronic viral myocarditis.

Inflammation and myocardial weakness, two major hallmarks of chronic viral myocarditis (VMC), often lead to dilated cardiomyopathy or chronic heart failure. It has been reported that indoleamine 2,3-dioxygenase-1 (IDO1) may play a pathogenic role in the progression of inflammatory diseases. Hence, the study is set out to investigate the potential role of IDO1 in chronic VMC by establishing a mouse model of VMC by intraperitoneally injected with coxsackievirus B3 (CVB3). After model establishment, the expression of IDO1 was determined by RT-qPCR and Western blot analysis. IDO1 was identified as an up-regulated gene in CVB3-induced VMC. Then, in order to elucidate the potential role of IDO1 in VMC, macrophages were isolated and treated with the overexpression plasmid of IDO1 or IDO1 inhibitor (1-MT). After that, these transfected macrophages were co-cultured with normal cardiomyocytes, followed by measurement of inflammatory factors and evaluation of cardiomyocyte injury. The overexpression of IDO1 was observed to significantly enhance the levels of interleukin (IL)-6, IL-1ß and tumor necrosis factor-α (TNF-α), as well as lactate dehydrogenase (LDH) activity and malondialdehyde (MDA) content. By contrast, the treatment of 1-MT in macrophages reversed the promoting effects of IDO1 on cardiomyocyte injury. Co-culture experiment showed that overexpressed IDO1 impaired cardiomyocyte, which was alleviated upon treatment of 1-MT. Taken together, the key findings of the present study provide evidence that 1-MT-mediated IDO1 suppression could potentially reduce inflammatory response in macrophages and consequently ameliorate cardiomyocyte injury in mice with VMC.

Quercetin supports cell viability and inhibits apoptosis in cardiocytes by down-regulating miR-199a.

Hypoxia-caused cardiocytes insults are closely correlated with ectopic expression of genes, which might be modulated by microRNAs (miRs). Quercetin exhibits a profound protective function against hypoxic damages in cardiomyocytes. Here, we aimed to investigate a possible underpinning. H9c2 cells were pre-administrated using quercetin before hypoxia treatment. The damages were assessed using viability, apoptosis and alteration of proteins associated with apoptosis and adenosine monophosphate-activated protein (AMPK) pathway. Transfection was conducted to enforce overexpression of miR-199a or silence of sirtuin 1 (sirt1) which were confirmed by qRT-PCR. Sirt1 protein was quantified by immunoblotting. A luciferase reporter was exploited to confirm the target relationship between miR-199a and sirt1 3'-untranslated region (3'-UTR). We found quercetin mitigated hypoxia-caused viability reduction and apoptosis with restoring apoptosis-associated protein and rescuing phosphorylation of AMPK. Quercetin flattened hypoxia-evoked overexpression of miR-199a. miR-199a abrogated the protective effects of quercetin against hypoxia-elicited damages. Quercetin elevated sirt1 which was repressed by hypoxia, while this effect was slight in miR-199a-overexpressed cells. miR-199a negatively mediated sirt1 expression through directly binding its 3'-UTR. Further, quercetin facilitated the phosphorylation of AMPK by up-regulating sirt1. Collectively, quercetin participated in repressing miR-199a which negatively modulated sirt1. Mechanically, through activating AMPK, quercetin protected cardiomyocytes cells against hypoxia-caused insults. Highlights Quercetin ameliorates hypoxia-evoked apoptosis and blockage of AMPK phosphorylation; The elevated miR-199a level is eased by quercetin, which might be a protective mechanism; Quercetin restores sirt1 level by repressing miR-199a expression; By mediating miR-199a and sirt1, AMPK phosphorylation is fortified by quercetin.

LncRNA SLC8A1-AS1 protects against myocardial damage through activation of cGMP-PKG signaling pathway by inhibiting SLC8A1 in mice models of myocardial infarction.

Extensive investigations into long noncoding RNAs (lncRNAs) in various diseases and cancers, including acute myocardial infarction (AMI) have been conducted. The current study aimed to investigate the role of lncRNA solute carrier family 8 member A1 antisense RNA 1 (SLC8A1-AS1) in myocardial damage by targeting solute carrier family 8 member A1 (SLC8A1) via cyclic guanosine 3',5'-monophosphate-protein kinase G (cGMP-PKG) signaling pathway in AMI mouse models. Differentially expressed lncRNA in AMI were initially screened and target relationship between lncRNA SLC8A1-AS1 and SLC8A1 was then verified. Infarct size, levels of inflammatory factors, biochemical indicators, and the positive expression of the SLC8A1 protein in AMI were subsequently determined. The expression of SLC8A1-AS1, SLC8A1, PKG1, PKG2, atrial natriuretic peptide, and brain natriuretic peptide was detected to assess the effect of SLC8A1-AS1 on SLC8A1 and cGMP-PKG. The respective contents of superoxide dismutase, lactate dehydrogenase (LDH), and malondialdehyde (MDA) were detected accordingly. Microarray data GSE66360 provided evidence indicating that SLC8A1-AS1 was poorly expressed in AMI. SLC8A1 was verified to be a target gene of lncRNA SLC8A1-AS1. SLC8A1-AS1 upregulation decreased levels of left ventricular end-systolic diameter, -dp/ dt max , interleukin 1ß (IL-1ß), IL-6, transforming growth factor α, nitric oxide, inducible nitric-oxide synthase, endothelial nitric-oxide synthase, infarct size, LDH activity and MDA content, and increased IL-10, left ventricular end-diastolic pressure and + dp/ dt max . Furthermore, the overexpression of SLC8A1-AS1 was noted to elicit an inhibitory effect on the cGMP-PKG signaling pathway via SLC8A1. In conclusion, lncRNA SLC8A1-AS1, by downregulating SLC8A1 and activating the cGMP-PKG signaling pathway, was observed to alleviate myocardial damage, inhibit the release of proinflammatory factors and reduce infarct size, ultimately protecting against myocardial damage.

Downregulated microRNA-224 aggravates vulnerable atherosclerotic plaques and vascular remodeling in acute coronary syndrome through activation of the TGF-ß/Smad pathway.

Recent studies have shown that circulating microRNAs (miRNA) play a critical role in diagnosing acute coronary syndrome (ACS). This study aims to investigate the effect of miR-224 on atherosclerotic plaques forming and vascular remodeling in ACS and its relationship with TGF-ß/Smad pathway. Myocardial infarction (MI) rat model was established and lentivirus vector of miR-224 inhibitor was prepared for investigating the effect of downregulated miR-224 on the contents of nitric oxide (NO) and endothelin-1 (ET-1), blood lipid levels and inflammatory factor levels in serum as well as the TGF-ß/Smad pathway. The rats suffering from MI had decreased survival rates and exhibited reduced levels of NO, high-density lipoprotein cholesterol, and lumen diameter, and Smad7 messenger RNA (mRNA) and protein expression; while had significantly increased ratio of heart weight or body weight, levels of ET-1, inflammatory factors, blood lipid indexes, vascular remodeling indexes, collagen volume fraction, vulnerable atherosclerotic plaque area, VCAM-1 and MMP-2 protein expression, TGF-ß, Smad2, Smad3, and Smad4 mRNA and protein expression. After inhibiting the TGF-ß/Smad pathway, the rats suffering from MI showed notably opposite trend. In conclusion, downregulation of miR-224 expression promotes the formation of vulnerable atherosclerotic plaques and vascular remodeling in ACS through activation of the TGF-ß/Smad pathway. Therefore, this study provides a new therapeutic target for ACS.

Tumour necrosis factor-α gene -308 G > A and -238 G > A polymorphisms are associated with susceptibility to irritable bowel syndrome and drug efficacy in children.

WHAT IS KNOWN AND OBJECTIVE: An imbalance in the genetically controlled pro- and anti-inflammatory cytokine production could potentially promote ongoing low-grade inflammation following an episode of acute gastroenteritis and, subsequently, could result in irritable bowel syndrome (IBS; post-infectious IBS, PI-IBS). Since there is very little known on the impact of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α) on IBS, we conducted the present study with aims of determining the correlation between TNF-α gene polymorphisms (-308 G > A and -238 G > A) and susceptibility to IBS and drug efficacy in children. METHODS: Diarrhoea-predominant IBS patients and healthy subjects were recruited for DNA extraction. The genotypes were tested using polymerase chain reaction-restriction fragment length polymorphism. In addition to conventional symptomatic treatments, Live Combined Bifidobacterium, Lactobacillus and Enterococcus Powder and Montmorillonite Powder were administered to all the patients participating in the study for consecutive 4 weeks. The efficacy was evaluated 2 weeks after the withdrawal of the drugs. The association between gene polymorphism and drug efficacy was analysed by means of binary logistic regression analysis. RESULTS: Patients in the IBS group were susceptible to IBS with GA genotype and A allele of -308 G > A so were those with AA genotype and A allele of -238 G > A. The symptoms were also alleviated following treatment. The cure rate of patients with GA genotype of -308 G > A and AA genotype of -238 G > A was low. These findings suggested that the haplotype AA could potentially be associated with the cure rate of IBS patients. GA genotype of -308 G > A, AA genotype of -238 G > A, enterobacteria and 5-hydroxytryptamine in serum may act adversely, whereas bifidobacterial may be beneficial to the efficacy of IBS treatment. WHAT IS NEW AND CONCLUSION: The above findings evidently suggest that the frequency of TNF-α gene -308 G > A carrying GA genotype and A allele and -238 G > A carrying AA genotype and A allele is higher in children with IBS. Additionally, GA genotype of -308 G > A and AA genotype of -238 G > A may act adversely to the efficacy of IBS treatment, which may be a reference index for predicting the curative effect of IBS.

Astragaloside IV Protects Rat Cardiomyocytes from Hypoxia-Induced Injury by Down-Regulation of miR-23a and miR-92a.

BACKGROUND/AIMS: Astragaloside IV (AS-IV), a traditional Chinese medicine isolated from Astragalus membranaceus, has been shown to exert cardioprotective effect previously. This study aimed to reveal the effects of AS-IV on hypoxia-injured cardiomyocyte. METHODS: H9c2 cells were treated with various doses of AS-IV for 24 h upon hypoxia. CCK-8 assay, flow cytometry/Western blot, and qRT-PCR were respectively conducted to measure the changes in cell viability, apoptosis, and the expression of miR-23a and miR-92a. Sprague-Dawley rats were received coronary ligation, and were administrated by various doses of AS-IV for 14 days. The infarct volume and outcome of rats followed by ligation were tested by ultrasound, arteriopuncture and nitrotetrazolium blue chloride (NBT) staining. RESULTS: We found that 10 µg/ml of AS-IV exerted myocardioprotective effects against hypoxia-induced cell damage, as AS-IV significantly increased H9c2 cells viability and decreased apoptosis. Interestingly, the myocardioprotective effects of AS-IV were alleviated by miR-23a and/or miR-92a overexpression. Knockdown of miR-23a and miR-92a activated PI3K/AKT and MAPK/ ERK signaling pathways. Bcl-2 was a target gene for miR-23a, and BCL2L2 was a target gene for miR-92a. In the animal model of myocardial infarction (MI), AS-IV significantly reduced the infarct volume, ejection fraction (EF), shortening fraction (FS) and LV systolic pressure (LVSP), and significantly increased left ventricular end-diastolic internal diameter (LVEDd). And also, the elevated expression of miR-23a and miR-92a in MI rat was reduced by AS-IV. CONCLUSION: AS-IV protected cardiomyocytes against hypoxia-induced injury possibly via down-regulation of miR-23a and miR-92a, and via activation of PI3K/AKT and MAPK/ERK signaling pathways.

Effects of MicroRNA-592-5p on Hippocampal Neuron Injury Following Hypoxic-Ischemic Brain Damage in Neonatal Mice - Involvement of PGD2/DP and PTGDR.

BACKGROUND/AIMS: This study aimed to explore the effect of microRNA-592-5p (miR-592-5p) on hypoxic-ischemic brain damage (HIBD)-induced hippocampal neuronal injury in a neonatal mouse model relative to the involvement of one target gene, PTGDR, and the PGD2/ DP signaling pathway. METHODS: A total of 30 neonatal mice aged 7 days were randomly selected to establish an HIBD mouse model. Hippocampal neuronal cells were transfected into a control group, a blank group, a negative control (NC) group, an miR-592-5p mimics group, an miR-592-5p inhibitors group, an siRNA-PTGDR group and an miR-592-5p inhibitors + siRNA-PTGDR group. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses were performed to detect the expression levels of miR-592-5p, PTGDR, DP2, Bcl-2 and Bax in tissues and cells. Cell proliferation, cell cycle and apoptosis were detected by MTT assay and flow cytometry, respectively. RESULTS: The expression levels of miR-592-5p and Bcl-2 decreased, while the expression levels of PTGDR, DP2 and Bax increased in the HIBD group. PTGDR is a target gene of miR-592-2p. Compared with the NC and blank groups, the expression levels of PTGDR, DP2 and Bax decreased, while the expression levels of miR-592-5p and Bcl-2 increased in the miR-592-5p mimics group. The siRNA-PTGDR group showed the same trend as that observed in the miR-592-5p mimics group, except with no difference in miR-592-5p expression. The miR-592-5p inhibitors group showed an opposite gene expression trend compared to that in the miR-592-5p mimics group. The S phase of the cell cycle was prolonged, the G1 phase was reduced, proliferation was increased, and the apoptosis rate was decreased in the siRNA-PTGDR and miR-592-5p mimics groups. Opposite trends for cell cycle, proliferation and apoptosis were observed in the miR-592-5p inhibitors group. CONCLUSIONS: Our study suggests that miR-592-5p upregulation protects against hippocampal neuronal injury caused by HIBD by targeting PTGDR and inhibiting the PGD2/DP signaling pathway.

Knockdown of long non-coding RNA MEG3 protects H9c2 cells from hypoxia-induced injury by targeting microRNA-183.

Acute myocardial infarction (AMI) occurs when blood supply to the heart is diminished (ischemia) for long time, and ischemia is primarily caused due to hypoxia. This study evaluated the effects of long non-coding RNA maternally expressed gene 3 (MEG3) on hypoxic rat cardiomyocyte-drived H9c2 cells. Hypoxic injury was confirmed by alterations of cell viability, migration, invasion, apoptosis, and hypoxia-inducible factor 1α (HIF-1α) expression. MEG3 level in hypoxic cells and effects of its knockdown on hypoxic cells were assessed. The interactions between MEG3 and miR-183 as well as miR-183 and p27 were investigated. In addition, the effects of aberrantly expressed MEG3, miR-183, and p27 on hypoxic cells along with the activation of PI3K/AKT/FOXO3a signaling pathway were all assessed. Results showed that hypoxia induced decreases of cell viability, migration and invasion, and increases of apoptosis and expressions of HIF-1α and MEG3. Knockdown of MEG3 decreased hypoxia-induced injury in H9c2 cells. Knockdown of MEG3 also increased miR-183 expression, which was identified as a target of MEG3. The effects of MEG3 knockdown on the hypoxic cells were reversed by miR-183 silence. p27 was identified as a target gene of miR-183, and its expression negatively regulated by miR-183. The mechanistic studies revealed that knockdown of p27 decreased hypoxia-induced H9c2 cell injury by activating PI3K/AKT/FOXO3a signal pathways. These findings suggest that knockdown of MEG3 alleviates hypoxia-induced H9c2 cell injury by miR-183-mediated suppression of p27 through activation of PI3K/AKT/FOXO3a signaling pathway.

Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by Targeting MicroRNA-139.

BACKGROUND/AIMS: Acute myocardial infarction (AMI) occurs when blood supply to the heart is diminished (ischemia) for long time; ischemia is primarily caused due to hypoxia. The present study evaluated the effects of long non-coding RNA H19 on hypoxic rat H9c2 cells and mouse HL-1 cells. METHODS: Hypoxic injury was confirmed by measuring cell viability, migration and invasion, and apoptosis using MTT, Transwell and flow cytometry assays, respectively. H19 expression after hypoxia was estimated by qRT-PCR. We then measured the effects of non-physiologically expressed H19, knockdown of miR-139 with or without H19 silence, and abnormally expressed Sox8 on hypoxia-induced H9c2 cells. Moreover, the interacted miRNA for H19 and downstream target gene were virtually screened and verified. The involved signaling pathways and the effects of abnormally expressed H19 on contractility of HL-1 cells were explored via Western blot analysis. RESULTS: Hypoxia induced decreases of cell viability, migration and invasion, increase of cell apoptosis and up-regulation of H19. Knockdown of H19 increased hypoxia-induced injury in H9c2 cells. H19 acted as a sponge for miR-139 and H19 knockdown aggravated hypoxia-induced injury by up-regulating miR-139. Sox8 was identified as a target of miR-139, and its expression was negatively regulated by miR-139. The mechanistic studies revealed that overexpression of Sox8 might decrease hypoxia-induced cell injury by activating the PI3K/AKT/mTOR pathway and MAPK. Besides, H19 promoted contractility of HL-1 cells. CONCLUSION: These findings suggest that H19 alleviates hypoxia-induced myocardial cell injury by miR-139-mediated up-regulation of Sox8, along with activation of the PI3K/AKT/mTOR pathway and MAPK.

Efficacy and safety of traditional chemotherapies for patients with ovarian neoplasm: a network meta-analysis.

BACKGROUND: Ovarian neoplasm is a kind of high risky cancer among female. This paper assessed the efficacy and safety of twelve therapies and figured out the superior chemotherapeutic drug for ovarian cancer through network meta-analysis (NMA). METHOD: Eligible randomized controlled trials (RCTs) were retrieved from electronic databases. Primary outcomes concerning efficacy, overall survival (OS) and progression-free survival (PFS), were presented as hazard ratio (HR) and the associated 95% credible interval(CrI), while outcomes concerning safety were assessed by odds ratio (OR) and the corresponding 95% CrI. Surface under the cumulative ranking curve (SUCRA) was calculated under each survival and safety outcome in order to show the rankings of tested therapies. RESULT: Electronic databases such as PubMed and Embase were searched to finally obtain 19 eligible studies of 16290 patients. In accordance of primary outcomes, when it came to 3-y PFS, paclitaxel/epirubicin/carboplatin (Pa/E/Ca) and pegylated liposomal doxorubicin/ paclitaxel/ carboplatin (PLD/Pa/Ca) were preferred compared to carboplatin (Ca) (HR= 0.80, 95% CrI= 0.67-0.96; HR= 0.83, 95% CrI= 0.69-0.99). According to 5y-PFS, Pa/E/Ca was notably better than Ca (HR= 0.80, 95% CrI= 0.65-0.99). As to adverse effects, Ca was superior to Pa/E/Ca in neuropathy (HR=0.05, 95% CrI=0.02-0.19). Pa/E/Ca showed high rankings in 3y-PFS (SUCRA=0.749), 5y-OS (SUCRA=0.738) and 5y-PFS (SUCRA=0.798) while (PLD/Pa/Ca) in 3y-OS (SUCRA=0.737), 5y-OS (SUCRA=0.687) and 5y-PFS (SUCRA=0.712). Besides, Pa/E/Ca ranked the third with a SUCRA of 0.661 in neutropenia. CONCLUSION: PLD/Pa/Ca, PLD/Ca and Pa/E/Ca are highly recommended as potential therapeutically choices for patients with ovarian cancer. But considering the lack of safety data for PLD/Pa/Ca, this intervention should be taken with caution.

Implantation of VVI pacemaker in a patient with dextrocardia, persistent left superior vena cava, and sick sinus syndrome: A case report.

BACKGROUND: Dextrocardia, or right-lying heart, is an uncommon congenital heart disease in which the apex of the heart is located on the right side of chest. Persistent left superior vena cava (PLSVA) is a rare venous anomaly that is often associated with the abnormalities of cardiac transduction system. A case with combination of dextrocardia, persistent left superior vena cava, and sick sinus syndrome has not been reported. METHODS: We used different techniques including cardiac color Doppler echocardiography, 24-hour Holter monitoring, and abdominal ultrasound to make a diagnosis and treated the patient by implanting a VVI pacemaker. RESULTS: A 50-year-old woman was admitted with a syncope. Angiography of the right atrium and superior vena cava, echocardiography, electrocardiography, and abdominal ultrasound revealed the presence of the combination of mirror image dextrocardia, PLSVA, and sick sinus syndrome. The complex structural anomalies presented great technical challenges for interventional treatments. After thorough examination and understanding of the structural anatomy and anomalies of the superior and inferior vena cava and cardiac chambers, we successfully treated this patient by implanting a VVI pacemaker. CONCLUSION: Physicians must be aware of the complexity of the morphological and anatomical structures of dextrocardia accompanying PLSVC. Given that the diagnosis of situs inversus was performed at a relatively advanced age, it is therefore important to make such a correct diagnosis followed by appropriate therapeutic intervention.

Elevated serum levels of ghrelin and TNF-α in patients with cyanotic and acyanotic congenital heart disease.

BACKGROUND: The levels of ghrelin and tumor necrosis factor alpha (TNF-α) are considered biological markers of congenital heart diseases (CHD). The present meta-analysis was conducted to investigate the clinical significance of serum levels of ghrelin and TNF-α in children with (CHD). METHODS: Chinese and English scientific literature databases were searched to retrieve published studies relevant to ghrelin, TNF-α and CHD. Manual search was additionally employed to identify other relevant studies from cross-references. The retrieved studies were screened on the basis of our stringent inclusion and exclusion criteria to select high quality case-control studies for meta-analysis. RESULTS: We initially retrieved 108 published studies (20 in Chinese and 88 in English) from database searches. Finally, 6 case-control studies (5 in English and 1 in Chinese) were enrolled in our meta-analysis, and contained a total of 160 cyanotic congenital heart disease (CCHD) patients and 215 acyanotic congenital heart disease (ACHD) patients, along with 162 healthy controls. The results of meta-analysis showed that serum levels of ghrelin and TNF-α in CCHD or ACHD children were significantly higher than those in healthy controls. CONCLUSIONS: Our meta-analysis results showed that serum levels of ghrelin and TNF-α are elevated in children with CHD, and could be used as effective biologic markers in early diagnosis of CHD.

The complete mitochondrial genome of Leizhou goat Capra hircus (Bovidae; Caprinae).

Leizhou goat (Capra hircus) is one of the famous native goat breed in China. In this study, the 16,651 bp complete nucleotide sequence of Leizhou goat mitochondrial genome was sequenced for the first time. It contained 22 tRNA genes, 2 ribosomal RNA genes, 13 protein-coding genes.

Cardioprotective Effect of MicroRNA-21 in Murine Myocardial Infarction.

INTRODUCTION: To investigate the cardioprotective effect of MicroRNA-21 (miR-21) in murine myocardial infarction (MI). METHODS: Forty C57BL/6 male mice were divided into sham group, MI group, LV-GFP group, and miR-21 group. Mice in the MI group, LV-GFP group, and miR-21 group were subjected to MI by left anterior descending artery (LAD) ligation, while chest was opened/closed without ligation in sham group. In MI group, expression of miR-21 in the MI area and its surrounding areas was detected at 1st, 2nd, and 4th week after experiment. Subsequently, lentivirus expressing miR-21 and lentivirus that did not express miR-21 were transfected into mice left ventricular cavity of miR-21 group and LV-GFP group, respectively. Cardiac function, MI size, miR-21 expression, collagen I level, fibronectin content, number of α-SMA-positive cells, number of apoptotic cells, apoptosis-related factors were compared between the three groups. RESULTS: Compared with sham group, miR-21 levels in MI group were significantly decreased in the 1st week and 2nd week, but were almost the same in the 4th week. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) in the miR-21 group improved compared to the LV-GFP group. In miR-21 group, myocardial infarct size reduced by 36.9% in comparison with LV-GFP group. Compared to sham group, miR-21 expression in the miR-21 group and LV-GFP group decreased significantly. In the miR-21 group, collagen I level, fibronectin content and number of α-SMA-positive cells of miR-21 decreased significantly compared to the LV-GFP group. The number of apoptotic cells in the MI areas of the miR-21 group was significantly less than the LV-GFP group. Compared with the LV-GFP group, Bcl-2 level and the ratio of Bcl-2 to Bax were significantly increased, and the levels of Bax and Caspase-3 decreased. CONCLUSIONS: Our results suggest miR-21 is an important regulatory molecule in the pathophysiology of MI.

Serum fetuin-A levels in patients with cardiovascular disease: a meta-analysis.

BACKGROUND: Fetuin-A (FA) suppresses arterial calcification, promotes insulin resistance, and appears to be elevated in patients with cardiovascular diseases (CVD), but the data is still inconsistent. To clarify the correlation between serum FA levels and the presence and severity of CVDs, we performed this meta-analysis. METHOD: Potential relevant studies were identified covering the following databases: PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases. Data from eligible studies were extracted and included in the meta-analysis using a random-effects model. RESULTS: Ten case-control studies, including 1,281 patients with CVDs and 2,663 healthy controls, were included. The results showed significant differences in serum levels of FA between the CVDs patients and the healthy controls (SMD=1.36, 95%CI: 0.37-2.36, P=0.007). Ethnicity-subgroup analysis implied that low serum FA levels are related to CVDs in Caucasians (SMD=1.73, 95%CI: 0.20-3.26, P=0.026), but not in Asians (SMD=1.04, 95%CI: -0.33-2.40, P=0.138). CONCLUSION: The data indicated that decreased serum FA level is correlated with the development of CVDs. FA might be clinically valuable for reflecting the progression of CVDs.