Nutrient deficiency patterns and all-cause and cardiovascular mortality in older adults with hypertension: a latent class analysis.

BACKGROUND: Previous researches examining the impact of dietary nutrition on mortality risk have mainly focused on individual nutrients, however the interaction of these nutrients has not been considered. The purpose of this study was to identify of nutrient deficiencies patterns and analyze their potential impact on mortality risk in older adults with hypertension. METHODS: We included participants from the National Health and Nutrition Examination Survey (NHANES) study. The latent class analysis (LCA) was applied to uncover specific malnutrition profiles within the sample. Risk of the end points across the phenogroups was compared using Kaplan-Meier analysis and Cox proportional hazard regression model. Multinomial logistic regression was used to determine the influencing factors of specific malnutrition profiles. RESULTS: A total of 6924 participants aged 60 years or older with hypertension from NHANES 2003-2014 was followed until December 31, 2019 with a median follow-up of 8.7 years. Various nutrients included vitamin A, vitamin B1, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, fiber, folate, calcium, magnesium, zinc, copper, iron, and selenium, and LCA revealed 4 classes of malnutrition. Regarding all-cause mortality, "Nutrient Deprived" group showed the strongest hazard ratio (1.42 from 1.19 to 1.70) compared with "Adequate Nutrient" group, followed by "Inadequate Nutrient" group (1.29 from 1.10 to 1.50), and "Low Fiber, Magnesium, and Vit E" group (1.17 from 1.02 to 1.35). For cardiovascular mortality, "Nutrient Deprived" group showed the strongest hazard ratio (1.61 from 1.19 to 2.16) compared with "Adequate Nutrient" group, followed by "Low Fiber, Magnesium, and Vit E" group (1.51 from 1.04 to 2.20), and "Inadequate Nutrient" group (1.37 from 1.03 to 1.83). CONCLUSIONS: The study revealed a significant association between nutrients deficiency patterns and the risk of all-cause and cardiovascular mortality in older adults with hypertension. The findings suggested that nutrients deficiency pattern may be an important risk factor for mortality in older adults with hypertension.

Interactive association of the dietary oxidative balance score and cardiovascular disease with mortality in older adults: evidence from NHANES.

Objectives: We conducted an assessment to explore potential associations of the dietary oxidative balance score (DOBS), cardiovascular disease (CVD), with all-cause mortality among older adults, while also exploring the potential moderating effect of DOBS on the relationship between CVD and mortality. Methods: This study included 9059 older adults (≥60 years) from NHANES 2003-2014. Determination of DOBS involves scoring the combination of 16 nutrients, comprising 2 pro-oxidants and 14 anti-oxidants. Cox regression analysis was used to assess the individual associations of CVD and DOBS status with all-cause mortality. Additional evaluations were conducted to assess the combined impact of CVD and DOBS status on mortality, and the interaction were estimated. Sensitivity analyses were performed by excluding participants who died within two years. Results: The findings demonstrated a significant association between pro-oxidant diet (lower DOBS) or CVD and elevated mortality risk among older adults. It is also suggested that older adults with CVD and pro-oxidant diet exhibit the highest risk of all-cause mortality (HR = 1.96, 95% CI: 1.64-2.34), compared to individuals without CVD who follow an antioxidant-rich diet. Further stratified analysis based on CVD status revealed a different pattern in the correlation between pro-oxidant diet and all-cause mortality risk (P for interaction = 0.015). The results of sensitivity analysis were consistent. Conclusions: The lower levels of DOBS and/or CVD were significantly associated with an increased risk of all-cause mortality in older adults. Notably, we also identified a significant interaction between DOBS and CVD affecting all-cause mortality.

Combined association of dietary fibre and cognitive function with all-cause and cause-specific mortality in older adults.

BACKGROUND: Dietary fibre and cognitive function are associated with the risk of mortality, respectively. Inadequate dietary fibre intake and cognitive impairment frequently co-occur in older adults, but the combined effect of dietary fibre and cognitive function on mortality remains unknown. The study was to investigate the combined effect of dietary fibre and cognitive function on mortality over a 13-year follow-up in a representative of older adults from the U.S. METHODS: We analyzed data from two cycles of the National Health and Nutrition Examination Survey (NHANES) 1999-2000 and 2001-2002 with mortality follow-up data through 13 December 2015 obtained from Public-use Linked Mortality Files. Low dietary fibre intake was defined as the lowest quartile of dietary fibre intake. Cognitive impairment was defined as below the median of Digit Symbol Substitution Test. The separate and combined effects of low dietary fibre intake and cognitive impairment on all-cause and cause-specific mortality were assessed in older adults using weighted Cox proportional hazard models adjusting for potential confounders. RESULTS: A total of 2012 participants (weighted sample was 32,765,094) aged 60 years and older were enrolled in the study. After a median follow-up of 13.4 years, 1017 participants (50.4%) were identified as all-cause deaths, including 183 (9.1%) participants dying from cancer, 199 (9.9%) participants dying from cardiovascular disease, and 635 (31.5%) participants dying from non-cancer/non-cardiovascular disease. Participants with low dietary fibre intake and cognitive impairment had nearly twice the risk of all-cause (HR, 2.030; 95% CI, 1.406-2.931) and non-cancer/non-cardiovascular (HR, 2.057; 95% CI, 1.297-3.262) mortality, and over triple cancer (HR, 3.334; 95% CI, 1.685-6.599) mortality, compared to those without both. CONCLUSIONS: The combination of low dietary fibre intake and cognitive impairment was associated with an increased risk of all-cause, cancer and non-cancer/non- cardiovascular mortality in older adults.

Key MessagesThe inadequate dietary fibre intake and cognitive impairment often coexist in older adults, but the combined effect of dietary fibre and cognitive function on mortality is still unknown.This study evaluated the combined effect of dietary fibre and cognitive impairment on mortality among older adults with a 13-year follow-up in the United States, based on the National Health and Nutrition Examination Survey (NHANES).The results provided evidence of the importance of early screening and intervention for dietary fibre intake and cognitive function, and suggested the joint effect of dietary fibre and cognitive function on mortality could be significant for public health in older adults.

Hypertension, dietary fiber intake, and cognitive function in older adults [from the National Health and Nutrition Examination Survey Data (2011-2014)].

Background: Dietary fiber was associated with hypertension (HYP) and cognitive function, but it was unknown whether the effect of HYP on cognitive function in older adults was modified by dietary fiber intake. Methods: We recruited 2,478 participants from the 2011-2012 and 2013-2014 National Health and Nutrition Examination Survey (NHANES), with cognitive performance measured by Registry for Alzheimer's disease (CERAD), the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST). Multivariate General linear model was used to estimate the interaction between dietary fiber intake and HYP status in association with low cognitive performance. Results: Among 2,478 participants, 36% was Controlled HYP, 25% was Low uncontrolled HYP, 11% was High uncontrolled HYP, and 86% was low dietary fiber intake. The association between HYP status and DSST impairment differed by dietary fiber intake for those with high uncontrolled HYP compared to those without HYP. Among participants with low dietary fiber intake, those with uncontrolled HYP had higher risk of DSST impairment compared to those without HYP [HYP ≥ 90/140: OR (95% CI), 1.68 (1.15-2.45); HYP ≥ 100/160: OR (95%CI), 2.05 (1.29-3.23)]; however, there was no association between HYP status and DSST impairment among participants with high dietary fiber intake. Moreover, the interaction of HYP status and dietary fiber intake on DSST was close to statistical significance (P for interaction = 0.057). Conclusions: Uncontrolled HYP was associated with poorer cognitive performance in older adults with low, but not high dietary fiber intake. Sufficient dietary fiber intake might be as a new nutrition strategy for the prevention of cognitive impairment in older adults with uncontrolled HYP.

Sacubitril Valsartan Enhances Cardiac Function and Alleviates Myocardial Infarction in Rats through a SUV39H1/SPP1 Axis.

Sacubitril valsartan (lcz696) has been demonstrated as a substitute for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for the treatment of heart failure. This research is aimed at examining the effects of lcz696 and its target molecules on myocardial infarction (MI). A rat model of MI was induced by left anterior descending artery ligation and treated with lcz696. Lcz696 treatment significantly reduced cardiac injury and heart failure, restored the left ventricular fractional shortening and ejection fraction, and reduced oxidative stress and inflammatory responses in rat myocardium. By analyzing the heart failure-related GSE47495 dataset and performing gene ontology (GO) functional enrichment analysis, we obtained histone lysine methyltransferase SUV39H1 and secreted phosphoprotein 1 (SPP1) as two molecules implicated in the oxidative stress and inflammation processes. An elevation of SUV39H1 whereas a decline of SPP1 were detected in cardiac tissues after lcz696 treatment. Enrichments of SUV39H1 and H3K9me3 at the SPP1 promoter were identified by chromatin immunoprecipitation assay. SUV39H1 catalyzed H3K9me3 modification to suppress the expression of SPP1. Preconditioning of SUV39H1 silencing blocked the protective roles of lcz696, but SPP1 silencing alleviated the myocardial injury. In conclusion, this study demonstrates that lcz696 enhances cardiac function and alleviates MI in rats through a SUV39H1/SPP1 axis.

Activated Partial Thromboplastin Time and Mortality in Coronary Artery Bypass Grafting Patients.

Background: To evaluate the prognostic value of preoperative activated partial thromboplastin time (APTT) in patients who underwent coronary artery bypass grafting (CABG). Methods: All data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The study population was divided to two groups according to the optimal cut-off value of APTT calculated by X-tile software, and Cox proportional hazard model was used to define independent effect of APTT on 4-year mortality. Survival curves were estimated by the Kaplan-Meier method, and the area under the receiver-operating characteristic curve (AUC) was calculated to compare APTT with other severity scores. Propensity score matching (PSM) analysis were applied to ensure the robustness of this study. Results: A total of 2,706 patients were included. The optimal cut-off value of APTT for 4-year mortality was 44 seconds. The Cox proportional hazard model showed that patients with APTT ≥ 44 had a significantly higher risk of all-cause death than those with APTT < 44 both before (HR (95% CI), 1.42 (1.16-1.74), P < 0.001) and after PSM (HR (95% CI), 1.47 (1.14-1.89), P = 0.003). The survival curves showed that patients with longer APTT had a significantly lower 1-year and 4-year cumulative survival probability. The ROC of APTT combined with other severity scores significantly increased predictive ability for 1-year and 4-year mortality. Conclusions: A longer APTT (≥44) was associated with a higher risk of mortality and can serve as a prognostic predictor in CABG patients.

Circular RNA Foxo3 Relieves Myocardial Ischemia/Reperfusion Injury by Suppressing Autophagy via Inhibiting HMGB1 by Repressing KAT7 in Myocardial Infarction.

INTRODUCTION: Myocardial infarction is coronary artery-related heart disease, and the leading cause of mortality globally. Circular RNAs (circRNAs) are a new type of regulatory RNAs and participate in multiple pathological cardiac progression. METHODS: However, the function of circFoxo3 in MI-induced myocardial injury remains obscure. RESULTS: Significantly, we identified that circFoxo3 was downregulated in the MI rat model and the overexpression of circFoxo3 ameliorated MI-induced cardiac dysfunction and attenuated MI-induced autophagy in rat model. Meanwhile, the overexpression of circFoxo3 repressed oxygen-glucose deprivation (OGD)-induced autophagy, apoptosis, inflammation, and injury of cardiomyocyte in vitro. Mechanically, we identified that the expression of KAT7 was reduced by circFoxo3 overexpression in cardiomyocytes. Meanwhile, the expression of HMGB1 was repressed by the depletion of KAT7 in cardiomyocytes. The enrichment of histone H3 lysine 14 acetylation (H3K14ac) and RNA polymerase II (RNA pol II) on HMGB1 promoter was inhibited by the knockdown of KAT7. Moreover, the overexpression of circFoxo3 suppressed HMGB1 expression and KAT7 overexpression rescued the expression of HMGB1 in cardiomyocytes. The enrichment of KAT7, H3K14ac, and RNA poly II on HMGB1 promoter was decreased by circFoxo3 overexpression, while the overexpression of KAT7 could reverse the effect. The overexpression of KAT7 or HMGB1 could reverse circFoxo3-attenuated cardiomyocyte injury and autophagy in vitro. Thus, we conclude that circular RNA circFoxo3 relieved myocardial ischemia/reperfusion injury by suppressing autophagy via inhibiting HMGB1 by repressing KAT7 in MI. DISCUSSION: Our finding provides new insight into the mechanism by which circFoxo3 regulates MI-related cardiac dysfunction by targeting KAT7/HMGB1 axis.

Sacubitril/valsartan (LCZ696) reduces myocardial injury following myocardial infarction by inhibiting NLRP3­induced pyroptosis via the TAK1/JNK signaling pathway.

The present study aimed to investigate the protective effects of sacubitril/valsartan (LCZ696) on ventricular remodeling in myocardial infarction (MI) and the effects of the inflammasome­mediated inflammatory response. First, a rat model was established. Animals were then treated with LCZ696 so that the histopathological changes associated with ventricular remodeling could be investigated. The serum levels of the inflammatory factors IL­18 and IL­1ß were also determined by ELISA. Immunofluorescence was used to investigate the ratio of pyroptosis following MI modelling. Western blotting and reverse transcription­quantitative PCR were used to detect the relative expression levels of proteins and mRNAs in the transforming growth factor ß­activated kinase­1 (TAK1)/JNK pathway and those associated with the NLR pyrin family domain containing 3 (NLRP3) inflammasome, respectively. The present study also investigated the regulatory mechanisms and associations between the TAK1 and JNK pathways, NOD­, leucine­rich repeat­ and the NLRP3 inflammasome, in H9C2 cells and myocardial cells from the rat model of MI. LCZ696 improved MI­induced myocardial fibrosis, rescued myocardial injury and suppressed the release of inflammatory factors. With regards to myocardial cell damage, pyroptosis in cardiomyocytes was observed. The in vitro experiments demonstrated that the overexpression of TAK1 promoted lysis of the N­terminal of GSDMD, thereby activating the NLRP3 inflammasome and promoting the conversion of pro­IL­1ß and pro­IL­18 into mature IL­1ß and IL­18, respectively. In contrast, the silencing of TAK1 inhibited the expression levels of the NLRP3 inflammasome. In summary, LCZ696 reduced the expression levels of the NLRP3 inflammasome, suppressed inflammatory responses, improved the ventricular remodeling and exhibited protective effects in the MI heart by inhibiting the TAK1/JNK signaling pathway.

Long non­coding RNA NORAD regulates angiogenesis of human umbilical vein endothelial cells via miR­590­3p under hypoxic conditions.

Dysregulation of angiogenesis can be caused by hypoxia, which may result in severe diseases of the heart, including coronary artery disease. Hypoxia­inducible factor 1 (HIF­1) modulates angiogenesis via the regulation of several angiogenic factors. However, the underlying mechanism of hypoxia­induced angiogenesis remains unknown. In the present study, it was hypothesized that long non­coding RNA (lncRNA) non­coding RNA activated by DNA damage (NORAD) may serve a role in the process of angiogenesis via the regulation of microRNA(miR)­590­3p under hypoxic conditions. The effect of NORAD and miR­590­3p on cell viability and properties associated with angiogenesis, including cell migration and tube formation in human umbilical vein endothelial cells (HUVECs) under hypoxic conditions, were assessed. Potential downstream angiogenic factors of miR­590­3p were also determined by molecular experiments. It was identified that NORAD expression was upregulated and miR­590­3p expression was downregulated in hypoxia­exposed HUVECs, and also in myocardial infarction (MI) left ventricle tissues in mice. Moreover, downregulation of NORAD expression resulted in decreased cell viability and angiogenic capacity, but further knocking down miR­590­3p expression reversed these alterations, resulting in increased cell migration and tube formation in HUVECs under hypoxic conditions for 24 h. It was demonstrated that NORAD overexpression also increased cell vitality and tube­formation capacity. Furthermore, NORAD was identified to bind with miR­590­3p directly, and miR­590­3p was shown to target certain proangiogenic agents, such as vascular endothelial growth factor (VEGF)A, fibroblast growth factor (FGF)1 and FGF2 directly. Therefore, the present results suggested that lncRNA NORAD may bind with miR­590­3p to regulate the angiogenic ability of HUVECs via the regulation of several downstream proangiogenic factors under hypoxia. Thus, the lncRNA NORAD/miR­590­3p axis may be a novel regulatory pathway in the angiogenic mechanisms in HUVECs, which highlights a potentially novel perspective for treating ischemia/hypoxia­induced angiogenic diseases.

Effects of nanoparticle-mediated delivery of pitavastatin on atherosclerotic plaques in ApoE-knockout mice and THP-1-derived macrophages.

The treatment of atherosclerosis remains complex. Pitavastatin serves an important role in the prevention and treatment of atherosclerosis. The present study aimed to investigate the effects of nanoparticle (NP)-mediated delivery of pitavastatin into atherosclerotic plaques as a novel treatment method for atherosclerosis. The results of the present study demonstrated that pitavastatin-NP was more effective in attenuating the size of atherosclerotic plaques and enhancing the stability of plaques in vitro compared with pitavastatin alone. In an apolipoprotein E (ApoE)-knockout mouse model of atherosclerosis, a single intravenous injection of fluorescein isothiocyanate-NP resulted in the delivery of NP into atherosclerotic plaques for up to 7 days post-injection. In ApoE-knockout mice and THP-1-derived macrophages, pitavastatin-NP attenuated the development of atherosclerosis, which was associated with regulating lipid metabolism, and inhibited the secretion of inflammatory markers compared with pitavastatin alone. Additionally, the treatment advantages of pitavastatin-NP were independent of lipid lowering. The results demonstrated that pitavastatin-NP administration was more effective in attenuating the development of atherosclerotic plaques compared with systemic administration of pitavastatin.

Crosstalk between endothelial cell-specific calpain inhibition and the endothelial-mesenchymal transition via the HSP90/Akt signaling pathway.

HYPOTHESIS: The role of non-cardiomyocytes in cardiac remodeling and fibrosis has not been totally understood until now. This study investigated if endothelial cell (EC)-specific calpain participates in myocardial endothelial injury via the endothelial- mesenchymal transition (EndMT) and in cardiac fibroblasts during cell proliferation, thereby contributing to cardiac fibrosis eventually. METHODS: in vitro cultured mouse cardiac ECs were induced with transforming growth factor (TGF)-ß1 (10 ng/ml) and calpain inhibitor III (20 µM) or Akt inhibitor (LY294002, 20 µM). Isolated cardiac fibroblasts were induced by TGF-ß1 and an HSP90 inhibitor (17AAG, 20 µM), and EndMT were analysed. Capn4-knockout (KO) specific to ECs of mice was generated. We induced the pathological process mimicking cardiac hypertrophy and fibrosis in both Capn4-KO mice and their wild-type littermates. The histological analysis was used to measure cardiomyocyte size and collagen contained in the heart. The immunofluorescence analysis was performed to demonstrate that the ECs went through the EndMT, transforming mesenchymal cells into fibroblasts and myofibroblasts. RESULTS: Capn4 deletion specific to ECs abrogated activity of both calpain 1 and calpain 2 in ECs, lowered the volume of cardiac collagen and cardiomyocytes size, and ameliorated myocardial dysfunction in the isoproterenol-treated cardiac fibrosis model. An ex vivo analysis of cardiomyocytes by Evans Blue staining revealed that isoproterenol increased cell death compared with the control, and Capn4-KO alleviated this result. Inhibiting calpain in cultured cardiac microvascular endothelial cells (MCECs) reversed the EndMT process, which was induced by TGF-ß1. Overexpression of calpastatin decreased the pathological EndMT process, showing that the cultured MCECs have more mesenchymal markers, such as α-smooth muscle actin (SMA), and fewer endothelial markers, such as VE-cadherin. Activating calpain elevated phosphorylated Akt in mice cultured ECs, and inhibiting calpain decreased phosphorylated Akt. Upregulation of phosphorylated Akt by calpain promoted the EndMT, whereas inhibiting calpain switched on the protective mechanism during the EndMT via the heat shock protein (HSP)90/Akt signaling way in cultured ECs. CONCLUSIONS: This study demonstrated a vital role of calpain in ECs for inducing myocardiocyte hypertrophy, cell death and the EndMT via the HSP90/Akt signaling pathway, thereby promoting cardiac fibrosis. The results indicate that inhibiting ECs calpain is a novel therapeutic target to retard cardiac fibrosis and has positive effects on heart failure.

Effects of Intracoronary Nicorandil on Myocardial Microcirculation and Clinical Outcomes in Patients with Acute Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The amelioration of myocardial reperfusion in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PPCI) remains a significant issue. OBJECTIVE: We conducted a meta-analysis of randomized controlled trials (RCTs) to better assess the effects of intracoronary nicorandil administration on myocardial microcirculation and clinical outcomes in these patients. METHODS: The meta-analysis was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. A literature search was performed in the PubMed, Embase, Cochrane Library, and Web of Science databases up to April 2019, with no time or language limitations. Pooled risk ratios (RRs) were calculated to evaluate the treatment effects. RESULTS: Seven RCTs involving a total of 562 patients were included. Compared with control, intracoronary nicorandil significantly reduced the incidence of thrombolysis in myocardial infarction (TIMI) grade ≤ 2 (RR 0.349; 95% confidence interval [CI] 0.199-0.611; P < 0.001) and TIMI myocardial perfusion grade ≤ 2 (RR 0.611; 95% CI 0.438-0.852; P = 0.004) and was associated with higher complete ST-segment resolution rates (RR 1.326; 95% CI 1.090-1.614; P = 0.005). However, no significant benefits were observed on clinical outcomes, including death (RR 0.370; 95% CI 0.085-1.618; P = 0.187), recurrent myocardial infarction (RR 0.507; 95% CI 0.156-1.655; P = 0.261), heart failure (RR 0.528; 95% CI 0.224-1.247; P = 0.145), and target lesion/vessel revascularization (RR 1.109; 95% CI 0.553-2.224; P = 0.770). CONCLUSIONS: Intracoronary nicorandil can significantly improve myocardial microcirculation in patients with AMI undergoing PPCI, but it failed to offer clinically significant benefits.

Human amnion mesenchymal stem cells attenuate atherosclerosis by modulating macrophage function to reduce immune response.

Mesenchymal stem cells (MSCs) show immunosuppressive activities and alleviate atherosclerosis (AS) formation in apolipoprotein E­knockout (apoE­KO) mice. Human amnion mesenchymal stem cells (hAMSCs), a particular population of mesenchymal stem cells, have been shown to have immunomodulatory abilities. The present study investigated the effects of hAMSCs treatment on early atherosclerotic plaque formation and the progression of established lesion in apoE­KO mice. In total, 36 mice were fed with a high­fat diet. Mice were subjected to hAMSCs­injection treatment simultaneously with high­fat diet (early treatment) or after 8 weeks of high­fat diet (delayed treatment). In each treatment, mice were divided into three groups: i) hAMSCs group with hAMSCs treatment; ii) PBS group injected with PBS; and iii) control group without injection. Histological results showed that the plaque area in the aortic arch of mice was significantly reduced after hAMSCs treatment in the early and delayed treatment groups. In addition, immunohistochemical analysis suggested that the accumulation of macrophages was significantly decreased after hAMSCs treatment. Similarly, the release of the pro­inflammatory cytokine tumor necrosis factor­α was also decreased, whereas the release of the anti­inflammatory cytokine interleukin­10 was increased. In addition, hAMSCs treatment suppressed the phosphorylation of p65 and inhibitor of κB­α, suggesting that NF­κB pathway was involved in the hAMSCs­mediated suppression of immune response. In conclusion, hAMSCs treatment was effective in reducing immune response, which is the one of the major causes of AS, eventually leading to a significant reduction in size of atherosclerotic lesions.

Treatment with verapamil for restoration of sinus rhythm in atrial fibrillation with rapid ventricular response: A case report.

RATIONALE: Atrial fibrillation (AF) is a common arrhythmia disease that can cause thromboembolic disease and/or heart failure, resulting in increased mortality. Propafenone, amiodarone, and flecainide are recommended for converting AF to sinus rhythm. Beta blockers, verapamil, diltiazem, and digoxin are recommended for controlling AF with fast ventricular rate (VR). In this case report, we found that verapamil successfully converted AF into sinus rhythm. PATIENT CONCERNS: A 92-year-old woman presented with fast VR AF with a history of coronary heart disease, hypertension, and diabetes. DIAGNOSES: Verapamil can successfully convert AF into sinus rhythm. INTERVENTIONS AND OUTCOMES: The patient was treated with amiodarone or propafenone, yet still had AF. After stopping amiodarone and propafenone, the patient was given verapamil to control the VR, and following 9 days of treatment the patient switched to sinus rhythm. When verapamil treatment was stopped, the patient experienced AF recurrence. Upon receiving verapamil again, the AF again converted into sinus rhythm. LESSONS: For the treatment of AF, nondihydropyridine calcium antagonists can be tried in the absence of antiarrhythmic drugs.

Association between serum uric acid levels and coronary artery disease in different age and gender: a cross-sectional study.

BACKGROUND: The association between uric acid (UA) and coronary artery disease (CAD) was controversial. It was still unclear how the UA level changes with age and gender. AIMS: To confirm the relationship between the change of UA with age and gender and CAD, especially in elderly people. METHODS: 8285 individuals were investigated. The changes of UA and hyperuricemia in female and male with age were analyzed. The associations of UA, and hyperuricemia with CAD in different age and sex were assessed. RESULTS: Individuals were stratified into four groups according to their age: ≤ 39 years; 40-59 years; 60-79 years, and ≥ 80 years. The level of UA and the proportion of hyperuricemia increased significantly with age in female (P < 0.001), but showed a downward trend in male (P < 0.001). After adjusting for confounding factors, hyperuricemia remained an independent risk factor for the incident of CAD in all women (P = 0.029). In ≥ 80 year groups of female, UA and hyperuricemia became independent risk factors for the incident of CAD in the univariate and multivariate logistic regression analyses (all P ≤ 0.001). DISCUSSION: The level of UA showed significantly different changes with age in different gender. The relationship between UA and CAD showed differences in different age and sex. CONCLUSIONS: There were significant correlations between UA, hyperuricemia, and CAD only in female, particularly in the ≥ 80 year elderly women, but not in men.

Effects of Cilostazol-Based Triple Antiplatelet Therapy Versus Dual Antiplatelet Therapy After Coronary Drug-Eluting Stent Implantation: An Updated Meta-Analysis of the Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: The results of studies on cilostazol-based triple antiplatelet therapy (TAT) after drug-eluting stent (DES) implantation were inconsistent. To assess the effects of TAT compared with dual antiplatelet therapy (DAT) after DES/second-generation DES implantation, we performed a meta-analysis of randomized controlled trials (RCTs). METHODS: All relevant studies evaluated were identified by searching the PubMed, EMBASE, Cochrane Library, and ISI Web of Science databases without time and language limitation. Subgroup analyses were performed to evaluate the efficacy and safety of TAT after second-generation DES implantation. RESULTS: Eleven RCTs involving a total of 4684 patients were included. The meta-analysis showed TAT was associated with significant beneficial effects on angiographic findings of in-stent restenosis [risk ratio (RR) 0.645, 95% confidence interval (CI) 0.470-0.885; P = 0.007], in-segment restenosis (RR 0.606, 95% CI 0.450-0.817; P = 0.001), in-stent late loss (RR - 0.095, 95% CI - 0.136 to - 0.054; P < 0.0001), in-segment late loss (RR - 0.100, 95% CI - 0.139 to - 0.061; P < 0.0001), target lesion revascularization (TLR) (RR 0.570, 95% CI 0.430-0.755; P < 0.0001), and target vessel revascularization (TVR) (RR 0.523, 95% CI 0.380-0.719; P < 0.0001). No significant difference was found in outcomes of all-cause death, cardiac death, definite/probable stent thrombosis (ST), non-fatal myocardial infarction (MI), overall bleeding, and major bleeding between the two groups, as well as some minor adverse effects including palpitations, thrombocytopenia, neutropenia, and hepatic dysfunction. However, the incidence rate of rash, gastrointestinal disorders, and headache was significantly higher in TAT. The second-generation DES subgroup showed similar results, except for the indicators of all-cause death (RR 2.161, 95% CI 1.007-4.635; P = 0.048) and hepatic dysfunction (RR 0.176, 95% CI 0.031-0.995; P = 0.049). CONCLUSIONS: Compared with DAT, cilostazol-based TAT can significantly improve the angiographic findings of in-stent and in-segment late loss, in-stent and in-segment restenosis, TLR, and TVR after DES/second-generation DES implantation. However, no benefits were observed in outcomes of all-cause death, cardiac death, ST, and MI.

MicroRNA-21 mediates high phosphate-induced endothelial cell apoptosis.

Hyperphosphatemia, the elevated level of inorganic phosphate (Pi) in serum, is associated with increased cardiovascular morbidities and mortality. The effects of high Pi on endothelial cells are not well studied. This study investigated high Pi-induced endothelial cell apoptosis and the role of microRNA-21. Mouse myocardial endothelial cells (MEC) were cultured in normal (1 mM) and high (5 mM) Pi conditions. Apoptosis was detected by TUNEL staining and flow cytometry. MicroRNA profiles of MEC response to changes in Pi concentration were obtained using gene expression arrays. Expression levels of the microRNA-21 target genes, programmed cell death gene 4 ( PDCD4), poly(ADP-ribose) polymerase ( PARP), and phosphatase and tensin homolog ( PTEN), as well as NF-κB were measured by Western blotting and RT-PCR. MicroRNA-21-specific inhibitors and mimics were used to study effects of microRNA-21 on MEC apoptosis and gene expression regulations. High Pi induced MEC apoptosis and upregulated microRNA-21 expression. MicroRNA-21-specific mimics reproduced high Pi-induced apoptosis in normal Pi medium, and microRNA-21 inhibitors ameliorated the high Pi induction of apoptosis, suggesting that microRNA-21 mediated high Pi-induced MEC apoptosis. The microRNA-21 targets PDCD4, PTEN, PARP, and NF-κB were significantly downregulated in high Pi conditions. High Pi-induced downregulation of PDCD4 was abolished by microRNA-21 inhibitors and selective ERK inhibitor (selumetinib) and was reproduced by microRNA-21 mimics. Inhibitors and mimics of microRNA-21 did not have effects on high Pi-induced NF-κB downregulation. Selumetinib blocked high Pi-induced NF-κB downregulation. MicroRNA-21 mediates high Pi-induced endothelial cell apoptosis, which involves an ERK1/2/microRNA-21/PDCD4 pathway. High Pi-induced downregulation of NF-κB expression is mediated by an ERK1/2 signaling-dependent but microRNA-21-independent mechanism.

Cardiac contractility modulation improves left ventricular systolic function partially via miR-25 mediated SERCA2A expression in rabbit trans aortic constriction heart failure model.

The purpose of this study was to investigate the underlying mechanism of cardiac contractility modulation (CCM) in improving trans aortic constriction (TAC)-induced heart failure (HF) left ventricular (LV) systolic function. A total of 25 New Zealand white rabbits were randomly divided into 5 groups: sham operation group (SHM), TAC-induced HF group (HF), TAC-induced HF followed by CCM stimulation group (HF + CCM), TAC-induced HF followed by injection of anti-miR-25 group (HF + anti-miR-25), TAC-induced HF followed by CCM stimulation and AAV9-miR-25 injection group (HF + CCM + miR-25). CCM current was performed 6 hours a day for 4 weeks. The left ventricle ejection fraction (LVEF) was measured by ultrasound. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used for measuring RNA and protein levels. The sarcoplasmic reticulum calcium ATPase (SERCA2A) and LVEF were reduced, while the miR-25 expression was improved in HF group compared to SHM group. Conversely, the SERCA2A and LVEF were improved, and the miR-25 reduced in the HF + CCM and the HF + anti-miR-25 groups compared to the HF group. Moreover, the SERCA2A and LVEF were reduced, while the miR-25 was improved in the HF + CCM + miR-25 group compared to the HF + CCM group. CCM is a potentially effective procedure for improving LV systolic function, which might partially by inhibiting miR-25 expression, further improved SERCA2A expression in TAC HF models.

Crocin prevents platelet­derived growth factor BB­induced vascular smooth muscle cells proliferation and phenotypic switch.

The phenotypic switch of vascular smooth muscle cells (VSMCs) is a major initiating factor for atherosclerotic cardiovascular diseases. Platelet­derived growth factor­BB (PDGF­BB) initiates a number of biological processes that contribute to VSMC proliferation and phenotypic switch. Crocin, a component of saffron, has been reported to inhibit atheromatous plaque formation. However, the effects of crocin on PDGF­BB­induced VSMC proliferation and phenotypic switch remain unclear. The aim of the present study was to investigate the role of crocin on PDGF­BB­induced VSMCs proliferation and phenotypic switch and its underlying mechanisms. Cell proliferation and markers of VSMCs phenotypic switch were measured using a Cell Counting Kit­8 assay and western blot analysis, respectively. The signaling pathways involved in the effects of crocin on VSMCs were validated by western blot analysis with or without the use of specific pathway inhibitors. Crocin significantly inhibited PDGF­BB­induced VSMCs proliferation compared with the PDGF­BB only group (P<0.05). In addition, crocin significantly abrogated the PDGF­BB­induced increase in contractile protein α­smooth muscle actin, calponin and decrease in synthetic proteins osteopontin (OPN) in a concentration dependent manner (P<0.05). In addition, crocin slowed PDGF­BB­induced Janus kinase (JAK)­signal transducer and activator of transcription 3 (STAT3) and extracellular signal­regulated kinase (ERK)/Kruppel­like factor 4 (KLF4) signaling activation in VSMCs. By applying the JAK inhibitor (AG490) and ERK1/2 inhibitor (U0126), the results suggested that the crocin inhibited PDGF­BB­induced VSMCs phenotypic switch through the JAK/STAT3 and ERK/KLF4 signaling pathways. These results suggested that crocin may effectively prevent PDGF­BB­induced VSMCs proliferation and phenotypic switch and may be a promising candidate for the therapy of atherosclerotic cardiovascular diseases.

The protease inhibitor E64d improves ox-LDL-induced endothelial dysfunction in human aortic endothelial cells.

Oxidized low-density lipoprotein (ox-LDL)-induced endothelial dysfunction in human vascular endothelial cells contributes to the development of atherosclerosis. E64d, a cysteine protease inhibitor, blocks the elastolytic activity of cathepsin essential for vascular matrix remodeling and reduces neurovascular endothelial apoptosis. The objective of this study was to investigate the effects and the underling mechanisms of E64d on ox-LDL-induced endothelial dysfunction in human aortic endothelial cells (HAECs). HAECs were treated with various concentrations of ox-LDL (0-200 mg/L) for 24 h with or without E64d. The results showed that E64d attenuated ox-LDL-induced increase in soluble intercellular adhesion molecule-1 (sICAM-1) concentration and reduction in endothelial nitric oxide synthase (eNOS) expression, prevented ox-LDL-induced reduction in cell viability and migration ability of HAECs. E64d decreased the protein expression of cathepsin B (CTSB), Beclin 1, and microtubule-associated protein light chain 3 (LC3)-II, but not p62. LC3 puncta and autophagosome formation were also reduced by E64d in HAECs. Moreover, E64d decreased the production of MDA and increased the activity of SOD. The results showed that E64d ameliorated ox-LDL-induced endothelial dysfunction in HAECs.