Upregulation of LncRNA UCA1 promotes cardiomyocyte proliferation by inhibiting the miR-128/SUZ12/P27 pathway.

Enhancing cardiomyocyte proliferation is essential to reverse or slow down the heart failure progression in many cardiovascular diseases such as myocardial infarction (MI). Long non-coding RNAs (lncRNAs) have been reported to regulate cardiomyocyte proliferation. In particular, lncRNA urothelial carcinoma-associated 1 (lncUCA1) played multiple roles in regulating cell cycle progression and cardiovascular diseases, making lncUCA1 a potential target for promoting cardiomyocyte proliferation. However, the role of lncUCA1 in cardiomyocyte proliferation remains unknown. This study aimed at exploring the function and underlying molecular mechanism of lncUCA1 in cardiomyocyte proliferation. Quantitative RT-PCR showed that lncUCA1 expression decreased in postnatal hearts. Gain-and-loss-of-function experiments showed that lncUCA1 positively regulated cardiomyocyte proliferation in vitro and in vivo. The bioinformatics program identified miR-128 as a potential target of lncUCA1, and loss of miR-128 was reported to promote cardiomyocyte proliferation by inhibiting the SUZ12/P27 pathway. Luciferase reporter assay, qRT-PCR, western blotting, and immunostaining experiments further revealed that lncUCA1 acted as a ceRNA of miR-128 to upregulate its target SUZ12 and downregulate P27, thereby increasing cyclin B1, cyclin E, CDK1 and CDK2 expression to promote cardiomyocyte proliferation. In conclusion, upregulation of lncRNA UCA1 promoted cardiomyocyte proliferation by inhibiting the miR-128/SUZ12/P27 pathway. Our results indicated that lncUCA1 might be a new therapeutic target for stimulating cardiomyocyte proliferation.

CircSorbs1 regulates myocardial regeneration and reduces cancer therapy-related cardiovascular toxicity through the Mir-99/GATA4 pathway.

Due to the cancer therapy-related cardiovascular toxicity, heart failure following cancer therapy has a significant mortality rate. Gene-targeted therapy promotes the re-entry of existing cardiomyocytes into the cell cycle to achieve myocardial regeneration, which is a promising strategy for preventing and treating heart failure after myocardial infarction. Circular RNAs (circRNAs) are considered as potential targets for myocardial regeneration due to their strong stability, resistance to degradation, and potential role in heart development and cardiovascular diseases. By comparing the myocardial tissue of mice in the sham operation group and the Doxorubicin therapy group (DOX), we observed a significant decrease in Cirsorbs expression in the DOX group. Cirsorbs was predominantly localized in cardiomyocytes and exhibited high conservation. Subsequent investigations revealed that Cirsorbs could promote myocardial proliferation and inhibit myocardial apoptosis. Mechanistic studies further demonstrated that Cirsorbs could bind to miR99 and reduce its expression level. Meanwhile, miR99 was found to bind to GATA4 mRNA and decrease its expression level. The binding of Cirsorbs to miR99 alleviated the repression of miR99, thereby enhancing GATA4 expression and the transcription of downstream cyclin A2 and cyclin E1. This, in turn, increased cardiomyocyte proliferation and reduced apoptosis. In conclusion, Cirsorbs holds promise as an effective target for myocardial regeneration in reducing cancer therapy-related cardiovascular toxicity.

Lipoprotein (a)-Related Inflammatory Imbalance: A Novel Horizon for the Development of Atherosclerosis.

PURPOSE OF REVIEW: The primary objective of this review is to explore the pathophysiological roles and clinical implications of lipoprotein(a) [Lp(a)] in the context of atherosclerotic cardiovascular disease (ASCVD). We seek to understand how Lp(a) contributes to inflammation and arteriosclerosis, aiming to provide new insights into the mechanisms of ASCVD progression. RECENT FINDINGS: Recent research highlights Lp(a) as an independent risk factor for ASCVD. Studies show that Lp(a) not only promotes the inflammatory processes but also interacts with various cellular components, leading to endothelial dysfunction and smooth muscle cell proliferation. The dual role of Lp(a) in both instigating and, under certain conditions, mitigating inflammation is particularly noteworthy. This review finds that Lp(a) plays a complex role in the development of ASCVD through its involvement in inflammatory pathways. The interplay between Lp(a) levels and inflammatory responses highlights its potential as a target for therapeutic intervention. These insights could pave the way for novel approaches in managing and preventing ASCVD, urging further investigation into Lp(a) as a therapeutic target.

Novel polymorphisms in CYP4A22 associated with susceptibility to coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) has become a worldwide public health problem. Genetic factors are considered important risk factors for CHD. The aim of this study was to explore the correlation between CYP4A22 gene polymorphism and CHD susceptibility in the Chinese Han population. METHODS: We used SNPStats online software to complete the association analysis among 962 volunteers. False-positive report probability analysis was used to confirm whether a positive result is noteworthy. Haploview software and SNPStats were used for haplotype analysis and linkage disequilibrium. Multi-factor dimensionality reduction was applied to evaluate the interaction between candidate SNPs. RESULTS: In overall and some stratified analyses (male, age ≤ 60 years or CHD patients complicated with hypertension), CYP4A22-rs12564525 (overall, OR = 0.83, p-value is 0.042) and CYP4A22-rs2056900 (overall, OR = 1.22, p-value is 0.032) were associated with the risk of CHD. CYP4A22-4926581 was associated with increased CHD risk only in some stratified analyses. FPRP indicated that all positive results in our study are noteworthy findings. In addition, MDR showed that the single-locus model composed of rs2056900 is the best model for predicting susceptibility to CHD. CONCLUSION: There are significant associations between susceptibility to CHD and CYP4A22 rs12564525, and rs2056900.

CYP4V2 rs56413992 C > T was associated with the risk of coronary heart disease in the Chinese Han population: a case-control study.

PURPOSE: The research aimed to detect the association between single nucleotide polymorphisms (SNPs) in CYP4V2 gene and coronary heart disease (CHD) risk. METHODS: This case-control study included 487 CHD subjects and 487 healthy individuals. Logistic regression was performed to analyze the connection between five SNPs in CYP4V2 (rs1398007, rs13146272, rs3736455, rs1053094, and rs56413992) and CHD risk, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the connection. RESULTS: As a result, we found that rs56413992 T allele (OR = 1.36, 95% CI = 1.09-1.70, p = 0.007) and CT genotype (OR = 1.40, 95% CI = 1.06-1.83, p = 0.017) were significantly associated with an increased risk of CHD in the overall analysis. Precisely, rs56413992 was linked to an elevated risk of CHD in people aged > 60, males, smokers and drinkers. The study also indicated that rs1398007 was linked to an increased CHD risk in drinkers. In addition, rs1053094 was correlated with a decreased risk of CHD complicated with diabetes mellitus (DM), and rs1398007 was correlated with a decreased risk of CHD complicated with hypertension (HTN). CONCLUSION: This study was the first to experimentally demonstrate that CYP4V2 rs56413992 was associated with the risk of CHD, which will provide a certain reference for revealing the pathogenesis of CHD.

Genetic Variants of CYP4F2 Associated with Ischemic Stroke Susceptibility in the Han Population from Southern China.

Background: The pathophysiological mechanism of ischemic stroke is complex. Traditional risk factors cannot fully or only partially explain the occurrence and development of IS. Genetic factors are getting more and more attention. Our study aimed to explore the association between CYP4F2 gene polymorphism and susceptibility to IS. Methods: A total of 1322 volunteers were enrolled to perform an association analysis through SNPStats online software. Using FPRP (false-positive report probability) to detect whether the result is a noteworthy finding. The interaction of SNP-SNP in IS risk was assessed by multi-factor dimensionality reduction. Statistical analysis of this study was mainly completed by SPSS 22.0 software. Results: Mutant allele "A" (OR = 1.24) and genotype "AA" (OR = 1.49) or "GA" (OR = 1.26) of CYP4F2-rs2108622 are risk genetic factors for IS. Rs2108622 is significantly associated with an increased risk of IS among subjects who are females, aging >60 years old, with BMI ≥24 kg/m2, and smoking or drinking volunteers. CYP4F2-rs3093106 and -rs3093105 are associated with susceptibility to IS among smoking, drinking subjects, or IS patients complicated with hypertension. Conclusion: CYP4F2-rs2108622, -rs3093106, and -rs3093105 are associated with an increased risk of IS.

Role of CYP19A1 Loci (rs28757157 and rs3751591) with Ischemic Stroke Risk in the Chinese Han Population.

Introduction: Ischemic stroke (IS) is a multifactorial and polygenic disease, which is affected by genetic factors. In this study, we explored the role of CYP19A1 single nucleotide polymorphisms (SNPs) in IS in the Chinese population. Methods: 1302 subjects (651 controls and 651 cases) were recruited in this case-control study. Four candidate SNPs (rs28757157 C/T, rs3751592 C/T, rs3751591 G/A, rs59429575 C/T) of CYP19A1 were selected by the 1000 genomes project database. The association between CYP19A1 SNPs and IS risk was assessed using logistic regression analysis with odds ratio (OR) and 95% confidence intervals (CIs). False-positive report probability (FPRP) analysis further verified the positive results. The interaction of SNP-SNP was analyzed by multi-factor dimensionality reduction (MDR) to predict is risk. Results: In the research, CYP19A1 loci (rs28757157 and rs3751591) were associated with the occurrence of IS. The two variants conferred an increased susceptibility to IS in the subjects aged over 60 years old, smokers and drinkers. Rs28757157 was related to the risk of IS in females, non-smokers and subjects with BMI less than 24, while rs59429575 was related to the risk of IS in males and subjects with BMI greater than 24. Conclusion: The study revealed that there is a significant association between CYP19A1 loci (rs28757157 and rs3751591) and IS risk in the Chinese Han population, providing a theoretical basis for further exploring its specific role in the pathogenesis of IS.

Role of pyroptosis in diabetic cardiomyopathy: an updated review.

Diabetic cardiomyopathy (DCM), one of the common complications of diabetes, presents as a specific cardiomyopathy with anomalies in the structure and function of the heart. With the increasing prevalence of diabetes, DCM has a high morbidity and mortality worldwide. Recent studies have found that pyroptosis, as a programmed cell death accompanied by an inflammatory response, exacerbates the growth and genesis of DCM. These studies provide a theoretical basis for exploring the potential treatment of DCM. Therefore, this review aims to summarise the possible mechanisms by which pyroptosis promotes the development of DCM as well as the relevant studies targeting pyroptosis for the possible treatment of DCM, focusing on the molecular mechanisms of NLRP3 inflammasome-mediated pyroptosis, different cellular pyroptosis pathways associated with DCM, the effects of pyroptosis occurring in different cells on DCM, and the relevant drugs targeting NLRP3 inflammasome/pyroptosis for the treatment of DCM. This review might provide a fresh perspective and foundation for the development of therapeutic agents for DCM.

Metoprolol Protects Against Arginine Vasopressin-Induced Cellular Senescence in H9C2 Cardiomyocytes by Regulating the Sirt1/p53/p21 Axis.

Cardiomyocyte senescence is involved in the pathological mechanism of cardiac diseases. Metoprolol is a ß1 receptor blocker used for the treatment of hypertension. Recent studies show that Metoprolol can protect cardiomyocytes against ischemia injury. The present study aims to investigate the protective effects of Metoprolol against arginine vasopressin (AVP)-induced cellular senescence in cultured cardiomyocytes. The cell proliferation assay and cytotoxicity lactate dehydrogenase assay showed that the highest tolerated dosage of Metoprolol in H9C2 cardiomyocytes was optimized as 10 µM. The enzyme-linked immunosorbent assay showed that Metoprolol significantly ameliorated the elevated level of the DNA oxidation product 8-hydroxy-2 deoxyguanosine. Metoprolol also decreased the percentage of senescence-associated ß-galactosidase positive cells and improved the telomerase activity under AVP exposure. Moreover, treatment with Metoprolol ameliorated the decreased intracellular nicotinamide phosphoribosyltransferase activity, nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NAD+/NADPH) ratio, and Sirtuin1 activity in cardiomyocytes by AVP. Finally, Metoprolol was able to downregulate the AVP-induced expression of acetylated p53 and p21. Taken together, our data reveal that Metoprolol protected the cardiomyocytes from AVP-induced senescence.

The protective effects of S14G-humanin (HNG) against streptozotocin (STZ)-induced cardiac dysfunction.

Excessive oxidative stress, inflammation, and myocardial hypertrophy have been associated with diabetic cardiomyopathy (DCM). S14G-humanin (HNG) is a potent humanin analogue that has demonstrated cytoprotective effects in a variety of cells and tissues. However, the pharmacological function of HNG in diabetic cardiomyopathy has not yet been reported. In the present study, we investigated the protective effects of HNG against streptozotocin (STZ)-induced cardiac dysfunction in diabetic mice. Myocardial hypertrophy in diabetic mice was determined using Wheat Gem Agglutinin (WGA) staining. The heart function was measured with Echocardiographic imaging. Levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) proteins in plasma were measured using enzyme-linked immunosorbent assay (ELISA) kits. Protein expression of Phosphorylated p38/p38 was determined using western blots. We found that HNG treatment attenuated the STZ-induced myocardial hypertrophy and significantly improved heart function. Also, its treatment proved effective as it reduced the levels of several myocardial injury indicators, including creatine kinase-MB (CK-MB), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and both the cardiac and plasma levels of TNF-α and IL-6, highlighting its effect on the STZ-induced myocardial injury. Lastly, HNG suppressed the activation of the p38/nuclear factor kappa-B (NF-κB) signaling pathway. S14G humanin possesses protective effects against streptozotocin-induced cardiac dysfunction through inhibiting the activation of the p38/NF-κB signaling pathway.

The Number of Patients with Acute Myocardial Infarction Decreased and Door-to-Balloon Time Delayed in COVID-19.

BACKGROUND: At present, COVID-19 is sweeping the world, and all countries are actively responding. During the COVID-19 epidemic, the treatment of patients with acute myocardial infarction (AMI) may be affected. METHODS: We reviewed data of patients with AMI from January 23 to April 23, 2020 (2020), and January 23 to April 23, 2019 (2019), who were admitted to two hospitals from Southern China. We collected clinical characteristics, comorbidities, treatment, prognosis, and key time segments to analyze. RESULTS: The total number of patients that had been diagnosed with AMI in the two hospitals was 218 in 2020 and 260 in 2019. The number of AMI patients that were admitted to hospitals per day decreased in 2020. The percentage of patients with AMI who refused hospitalization in 2020 was significantly higher than that in 2019 (5.0% vs 1.5%, p=0.028). There is no statistical difference in symptoms of the first medical contact (S2FMC) time between 2020 and 2019 (p=0.552). Door-to-balloon (D2B) time of ST-elevation myocardial infarction (STEMI) patients who were treated with a primary percutaneous coronary intervention (pPCI) in 2020 was 79 (63.75-105.25) mins, while D2B time in 2019 was 57.5 (41.5-76.5) mins, which was statistically different from the two groups. CONCLUSIONS: COVID-19 had an impact on the number of AMI patients who were admitted to hospitals and the time of treatment. During the COVID-19 epidemic, the number of AMI patients that were admitted to hospitals per day was decreased, while the percentage of AMI patients that refused therapy in these two hospitals increased, and the D2B time of STEMI patients was also delayed.

MiR-30d inhibits cardiomyocytes autophagy promoting ferroptosis after myocardial infarction.

BACKGROUND: To investigate the effect of microRNA-30d (miR-30d) on autophagy and reveal the mechanism of autophagy promoting ferroptosis in H9C2 cells. METHODS: First, we detected miR-30d expression of myocardial tissue in the sham and myocardial infarction (MI) group, and then analyzed by biochemical analysis and luciferase Genetic experiments to confirm its downstream target gene of. After using Lentivirus-ATG5 (LV-sh-ATG5) to effectively inhibit autophagy, in order to further clarify the possible mechanism of autophagy leading to ferroptosis in H9C2 cells, we have tested the relevant indicators ferroptosis. RESULTS: We first found that miR-30d expression was down-regulated in myocardial tissue after MI, while autophagy increased, and autophagy was reduced when miR-30d was overexpressed, and then analyzed by biochemical analysis and luciferase Genetic experiments confirmed that ATG5 was a downstream target gene of miR-30d. After using Lentivirus-ATG5 (LV-shATG5) to effectively inhibit autophagy and up-regulate the expression of FTH1 and GPX4 in H9C2 cells, reduce the content of MDA, increase the content of GSH, and increase the activity of GPX4, suggesting that autophagy after MI may promote ferroptosis in H9C2 cells. CONCLUSIONS: The expression of miR-30d decreased in cardiomyocytes after MI and which can inhibit autophagy by binding to ATG5. Furthermore, autophagy after MI may promote ferroptosis.

Association of IL-10-1082A/G polymorphism with cardiovascular disease risk: Evidence from a case-control study to an updated meta-analysis.

BACKGROUND: Previous studies have generated controversial results about the association of interleukin 10 (IL-10) gene polymorphisms (-1082G/A) in the progression of cardiovascular disease (CVD). Therefore, this study processed a systemic meta-analysis to verify this association. METHODS: The publication studies on the IL-10 (-1082G/A) polymorphism and CVDs risk were obtained by searching PubMed and Embase databases. We analyzed the genotype data for meta-analysis. The results were evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). Meanwhile, our meta-analysis was also performed sensitivity analyses, heterogeneity test, and identification of publication bias. RESULTS: The present meta-analysis suggested that the risk with allele G is lower than with allele A for CVD. The G allele of IL-10 (-1082) could increase the risk of CVDs in the 31 case-control studies for all genetic models. (OR = 1.10, 95% CI: 1.04-1.15 for the allele model A vs. G; OR = 0.87, 95% CI: 0.72-1.04 for the dominant model GG+AG vs. AA; OR = 1.03, 95% CI: 1.02-1.05 for the recessive model GG vs. AG + AA; OR = 1.06, 95% CI = 1.03-1.10 for the homozygote comparison model GG vs. AA; and OR = 0.88, 95% CI = 0.73-1.06 for the heterozygote comparison model AG vs. AA). CONCLUSIONS: In genetic models, the association between the IL-10 (-1082G/A) polymorphism and CVDs risk was significant. This meta-analysis proposes that the IL-10 (-1082G/A) polymorphism may serve as a risk factor for CVDs.

Effects of CDKN2B-AS1 polymorphisms on the susceptibility to coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) is one of the most severe cardiovascular diseases. Cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) is a significant susceptibility locus for cardiovascular disease by regulating inflammation response and cell cycle. The aim of this study was to assess whether CDKN2B-AS1 polymorphisms are associated with CHD risk in the Chinese Han population. METHODS: A total of 501 CHD patients and 496 healthy controls were recruited from Central South University Xiangya School of Medicine Affiliated Haikou Hospital, five CDKN2B-AS1 polymorphisms (rs10115049, rs75227345, rs2383205, rs10738606, and rs1333049) were analyzed by the Agena MassARRAY platform. The association of CDKN2B-AS1 polymorphisms and CHD risk was determined by odd ratios (OR) and 95% confidence intervals (CI) using logistic regression. RESULTS: CDKN2B-AS1 rs10738606 was significantly associated with CHD under codominant (p = .03), dominant (p = .019), recessive (p = .010), additive (p = .003), and allele (p = .003) models. Gender-based subgroup tests showed that four polymorphisms (rs75227345, rs2383205, rs10738606 and rs1333049) were associated with CHD in males (p < .05). And age-based subgroup tests indicated that rs2383205 and rs10738606 were associated with CHD among individuals, respectively (p < .05). For CHD patients, rs1333049 decreased the risk of diabetes under heterozygote (p = .014) and dominant (p = .024) models. CONCLUSIONS: In conclusion, CDKN2B-AS1 polymorphisms were associated with CHD risk in the combined or subgroup tests, suggesting an important role of CDKN2B-AS1 in CHD susceptibility.

CYP17A1 Polymorphisms Are Linked to the Risk of Coronary Heart Disease in a Case-Control Study.

BACKGROUND: Cytochrome P450 17A1 (CYP17A1) catalyzes the formation and metabolism of steroid hormones and is required for cortisol and androgens. There is increasing evidence that CYP17A1 plays an important role in the development of coronary heart disease (CHD). However, the association of CYP17A1 polymorphisms and CHD susceptibility is still not clear. METHODS: We conducted a case-control study with 396 CHD cases and 461 healthy controls from Hainan province, China. Using the Agena MassARRAY platform, we genotyped 4 genetic variants (rs3740397, rs1004467, rs4919687, and rs3781286) in CYP17A1. Logistic regression analysis was used to assess the association of CYP17A1 polymorphisms with CHD risk by odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: It showed that A allele of CYP17A1 rs4919687 carried with a 1.59-fold increased risk of CHD (OR = 1.59; 95% CI = 1.26-1.99; P < 0.001). Also, rs4919687 was significantly associated with CHD risk under various models (homozygote: OR = 3.60; 95% CI = 1.64-7.83; P = 0.001; dominant: OR = 1.51; 95% CI = 1.06-2.13; P = 0.021; recessive: OR = 3.28; 95% CI = 1.51-7.14; P = 0.003; additive: OR = 1.56; 95% CI = 1.17-2.07; P = 0.002). Moreover, analysis showed that Ars1004467 Ars4919687 haplotype was a protective factor of CHD (OR = 0.64; 95% CI = 0.48-0.86; P = 0.002). CONCLUSIONS: Our study suggests that CYP17A1 polymorphisms are associated with CHD susceptibility in the Hainan Han Chinese population.

Genetic analysis of the relation of telomere length-related gene (RTEL1) and coronary heart disease risk.

BACKGROUND: Regulator of telomere elongation helicase 1 (RTEL1), a telomere length-related gene, is closely linked to cancer and age-related diseases. The aim of this study was to investigate the association between genetic polymorphisms in the RTEL1 gene and coronary heart disease (CHD) risk. METHODS: In this case-control study, which includes samples from 596 CHD patients and 603 healthy controls, five SNPs in RTEL1 were selected. The genotypes were studied using the Agena MassARRAY platform, and the statistical analyses were performed using the chi-square and Fisher's exact tests, genetic model analysis, and haplotype analysis. RESULTS: In the allele model, using the chi-square test, we found that the patients with the "G" allele of rs6010620 and the "C" allele of rs4809324 in the RTEL1 gene showed a decreased risk of CHD once the results were adjusted for age and gender. In the genetic model, logistic regression analyses revealed that the rs6010620 polymorphism conferred a decreased risk of CHD in the codominant model (OR = 0.52, 95% CI: 0.31-0.88, p = 0.007 for the "G/G" genotype) and the recessive model (OR = 0.49, 95% CI: 0.30-0.80, p = 0.004 for the "G/G" genotype). In addition, the haplotype "Grs6010620 Trs6010621 Trs4809324 " of RTEL1 was associated with a 0.03-fold decreased risk of CHD once the results were adjusted for age and gender (OR = 0.03, 95% CI: 0.01-0.12, p < 0.001). CONCLUSION: Our findings have demonstrated that the genetic variants of RTEL1 may have a protective role against CHD risk.

Ghrelin expression and significance in 92 patients with atrial fibrillation.

OBJECTIVE: Ghrelin is a polypeptide that is closely associated with many cardiovascular diseases, such as hypertension, atherosclerosis, and heart failure. This article aims to understand the expression of ghrelin in patients with atrial fibrillation (AF). METHODS: A total of 182 patients with non-valvular heart diseases were recruited, among whom 92 had AF and 90 had sinus arrhythmia (SA). The serum ghrelin amount was tested by the ELASA method. Moreover, blood sugar, lipids, liver function, and renal function were tested. All recruited patients underwent echocardiographic examination following admission. Three cardiac cycles were observed under continuous exhalation. The left atrial diameter (LAD) and the left ventricular ejection fraction (LVEF) were measured and averaged. Patients with AF received conventional treatment, and the aforementioned parameters were re-measured after 8 weeks. The results were statistically analyzed. RESULTS: The serum ghrelin level in the patients in the AF group (199.55±79.59 pg/mL) was lower than that in the patients in the SA group (313.89±71.13 pg/mL, p<0.01), whereas the serum ghrelin level in those in the paroxysmal AF group (224.44±72.33 pg/mL) was higher than that in those in the persistent AF group (176.00±79.88 pg/mL, p<0.01). There was a positive correlation between the serum ghrelin level and LVEF in the patients in the AF group (r=0.704, p=0.046). After treatment, the serum ghrelin level and LVEF in the patients in the AF group significantly increased, whereas LAD decreased. CONCLUSION: The serum ghrelin level in patients with AF was reduced, and after treatment, it significantly increased. There was a positive correlation between the serum ghrelin level and LVEF in the patients in the AF group.

Protective Effects of Pterostilbene Against Myocardial Ischemia/Reperfusion Injury in Rats.

Pterostilbene (PTB) has been suggested to protect against myocardial ischemia/reperfusion (MI/R) injury. Gas6/Axl signaling has been suggested to play an important role in cell survival. However, the interaction between PTB and Gas6/Axl signaling in MI/R remains unclear. This study aims to evaluate the role of Gas6/Axl signaling in the protective effects of PTB against MI/R injury. In experiment 1, the rats were subjected to 30 min of ischemia, followed by 3, 6, and 12 h of reperfusion, respectively. In experiment 2, the rats were administered intraperitoneally with PTB or vehicle and subjected to MI/R injury. The results suggested that the expression of Gas6 and Axl decreased significantly after MI/R injury. PTB treatment conferred a cardioprotective effect with an improved post-ischemic cardiac function, a reduced myocardial infarct size, and decreased lactate dehydrogenase and creatine kinase-MB in the serum, a decreased oxidative stress and inflammation, and a reduced number of apoptotic cardiomyocytes. Moreover, PTB treatment up-regulated the expression of Gas6, Axl, and Bcl-2 and down-regulated Bax expression. Our findings suggest that PTB treatment exerts cardioprotection against MI/R injury via attenuating inflammatory response, oxidative stress, and apoptosis and up-regulating the expression of Gas6 and Axl. The application of PTB may be a new strategy for the treatment of MI/R injury.

Losartan Attenuates Myocardial Endothelial-To-Mesenchymal Transition in Spontaneous Hypertensive Rats via Inhibiting TGF-ß/Smad Signaling.

BACKGROUND: Losartan plays an important role in the inhibition of myocardial fibrosis. But the underlying mechanism is not entirely clear. Emerging evidences have indicated that endothelial-to-mesenchymal transition (EndMT) plays a crucial role in cardiac fibrosis. Here the present study aims to first investigated the effect of Losartan on EndMT in cardiac fibrosis of spontaneous hypertensive rats (SHRs). METHODS: Male SHRs were randomly divided into three groups and fed for 12 weeks, namely the SHR group (Group S), the Losartan-treated group (Group L) and the Prazosin-treated group (Group P). Wistar-Kyoto rats served as controls (Group W). The histological changes were evaluated by Masson's trichrome. Co-expression of CD31 and fibroblast-specific protein 1 (FSP1) were used as the markers of EndMT through immunofluorescence. The expressions of FSP1, CD31, TGF-ß, Smad were detected by Western blot analysis. RESULTS: It was identified that elevated blood pressure induced a significant increase in myocardial fibrosis and EndMT in SHRs, which was reversed by Losartan and Prazosin treatment. Furthermore, the activity of TGF-ß/Smad signaling was detected in the four groups. TGF-ß/Smad signaling was activated in SHRs and suppressed by Losartan or Prazosin treatment. Losartan exhibited more efficiently than Prazosin in inhibiting TGF-ß/Smad signaling activation, EndMT and myocardial fibrosis. CONCLUSION: These results showed that EndMT played an important role in promoting hypertensive cardiac fibrosis, and that losartan could suppress cardiac fibrosis through the inhibition of EndMT via classical TGF-ß/Smad pathway.

Effects of Ang â ¡ perfusion on transmural heterogeneous of Cx43 in acute myocardial ischemia reperfusion.

OBJECTIVE: To observe the effects of angiotensin Ⅱ(Ang Ⅱ) perfusion on transmural heterogeneity of Cx43 expression in the rabbit model with acute myocardial ischemia reperfusion (MIR), and investigate the role of rennin-angiotensin system in malignant ventricular arrhythmia induced by MIR. METHODS: Twenty rabbits were randomly divided into MIR group (n = 10) and Ang Ⅱ group (n = 10). MIR model was produced with traditional ligation and opening of the anterior descending coronary artery in all animal. The hearts in vitro in the MIR group and the Ang Ⅱ group were perfused with simply improved Tyrode's solution and containing Ang Ⅱ Tyrode's solution respectively. 90% monophasic action potential repolarization duration, transmural dispersion of repolarization, Cx43 protein (Cx43-pro) and mRNA (Cx43-Cq) expression in subepicardial, midmyocardial and subendocardial myocardium were measured in both groups. The greatest differences of Cx43-pro and Cx43-Cq among three myocardial layers were calculated and shown with ΔCx43-pro and ΔCx43-Cq respectively. RESULTS: After Ang Ⅱ perfusion, 90% monophasic action potential repolarization duration among three myocardial layer were significantly prolonged (P < 0.05 and P < 0.01), and transmural dispersion of repolarization also significantly increased compared with the MIR group (P < 0.05). Compare with the MIR group, three myocardial Cx43-pro and Cx43-Cq expression in the Ang Ⅱ group were significantly decreased (P < 0.05 and P < 0.01), but ΔCx43-pro and ΔCx43-Cq were significant increased. CONCLUSIONS: Renin-angiotensin system increases transmural heterogeneity of Cx43 expression in the rabbit model with MIR by Ang Ⅱ, and enlarge transmural dispersion of repolarization among three myocardial layers of left ventricular which induces malignant ventricular arrhythmia.