BackgroundOxidized low-density lipoprotein (ox-LDL) can induce endothelial injury and plays a vital role in the procession and development of atherosclerosis. Little is known regarding whether Wnt/β-catenin pathway is involved in ox-LDL-induced endothelial injury or whether it further promotes atherosclerosis via increased oxidative stress. This study aimed to investigate the role of Wnt/β-catenin pathway in ox-LDL-induced vascular endothelial injury and determine whether pigment epithelium-derived factor (PEDF) could alleviate ox-LDL-induced endothelial injury by inhibiting Wnt/β-catenin pathway.MethodsInjury of human umbilical vein endothelial cells (HUVECs) was evaluated with an MTT assay, by monitoring lactate dehydrogenase (LDH) release and determining the apoptotic ratio. The expression of β-catenin (non-phosphorylated-β-catenin), disheveled-1 (Dvl-1) and Cyclin D1 was analyzed with western blotting and quantitative real-time PCR. Oxidative stress status was assessed by measuring the levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO).ResultsExposure of HUVECs to ox-LDL led to a decrease in cell viability and an increase in LDH release and apoptosis with concomitant enhancement of oxidative stress, as assessed by increased ROS and MDA generation, as well as decreased SOD activity and NO levels. Similar to lithium chloride (LiCl, a Wnt/β-catenin pathway activator), ox-LDL up-regulated the expression of β-catenin, Dvl-1 and Cyclin D1, markers of Wnt/β-catenin pathway activation. However, ox-LDL-induced activation of Wnt/β-catenin pathway, as well as ox-LDL-induced cell injury and oxidative stress, were synergistically promoted by LiCl and mitigated by Dickkopf 1 (DKK-1), an inhibitor of Wnt/β-catenin pathway. Additionally, ox-LDL-induced HUVEC injury and apoptosis, oxidative stress and activation of Wnt/β-catenin pathway were suppressed by PEDF, while they were further strengthened by a small interfering RNA of PEDF.ConclusionWnt/β-catenin pathway may mediate ox-LDL-induced endothelial injury via oxidative stress, and PEDF ameliorates endothelial injury by suppressing Wnt/β-catenin pathway and subsequently reducing oxidative stress.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-017-0407-8) contains supplementary material, which is available to authorized users.
Background: The population of older adults is growing rapidly with the increasing pace of aging worldwide. The triglyceride glucose (TyG) index has been a convenient and reliable surrogate marker of insulin resistance (IR). This study aimed to determine the association between the TyG index and arterial stiffness assessed by brachial-ankle pulse wave velocity (baPWV) in Chinese older adults.Methods: A total of 2,035 participants aged 60 years or above were enrolled. Demographic, anthropometric, and cardiovascular risk factors were collected. TyG index was calculated using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Arterial stiffness was measured using baPWV.Results: The participants, with the mean [standard deviation (SD)] age of 71.32 (6.75) years, the female proportion of 39.65%, the mean (SD) baPWV of 1,998 (437) cm/s, and the mean (SD) TyG index of 8.86 (0.54), were divided into four groups according to TyG index quartiles. Age-adjusted baPWV presented an increasing trend according to TyG index quartiles. In the fully adjusted linear regression model, the baPWV increased 49 cm/s, with the 95% confidence interval (CI) from 24 to 75 cm/s, per-SD increase in the TyG index. In the fully-adjusted logistic regression model, the odds ratio (95% CI) of high baPWV (>75th percentile) was 1.32 (1.09, 1.60) for each SD increase in the TyG index. The generalized additive model analysis also confirmed the significant association of the TyG index with baPWV and high baPWV.Conclusion: The TyG index is significantly associated with arterial stiffness assessed by baPWV in Chinese older adults.
Background The Mini-Mental State Examination (MMSE) is the most widely used instrument to test cognitive functioning. The present study prospectively investigated the association between MMSE scores, MMSE domains, and all-cause mortality. Methods A total of 2134 participants aged 60 years or over, selected from one urban community-dwelling population in China, were enrolled in the study. The cognitive test was performed by use of the MMSE at baseline, and covariates were recorded simultaneously. Cox regression models were used for examining the cognitive function, expressed by different MMSE transformations, and all-cause mortality. After followed up for a median of 10.8 years (ranging from 1.0 to 11.3 years), loss to follow-up was 13.1% and 1854 individuals were finally included in the analyses. Results The subjects had the mean (SD) age of 71.01 (7.00) years, and 754 (40.67%) of them were women. Per point increase on MMSE scores was associated a 4% decreased risk of all-cause mortality [hazard ratio (HR): 0.96; 95%confidence interval (CI): 0.93–0.98]; compared to MMSE scores of ≥24, MMSE scores of < 24 was associated with a 43% increased risk of all-cause mortality (HR: 1.43; 95% CI: 1.05–1.95); compared to MMSE scores of 30, MMSE scores of 27–29 (HR: 1.27; 95% CI: 0.89–1.82), 24–26 (HR: 1.30; 95% CI: 0.86–1.99), and < 24 (HR: 1.79; 95% CI: 1.15–2.77) had a graded increase in risk of all-cause mortality (p for trend =0.003). Of MMSE domains, orientation to time (HR: 2.00; 95% CI: 1.29–3.11), attention and calculation (HR: 1.49; 95% CI: 1.16–1.92), recall (HR: 2.59; 95% CI: 1.22–5.47), and language (HR: 1.68; 95% CI: 1.25–2.26) were significantly associated with all-cause mortality in the unadjusted model; for one increase in the number of impaired MMSE domains, the unadjusted HR (95% CI) of mortality is 1.51 (1.38, 1.65), and the HR (95% CI) of mortality is 1.12 (1.01, 1.25) with full adjustment; compared to 0 and 1 impaired MMSE domains, the HRs of all-cause mortality associated with 2, 3, 4, and ≥ 5 impaired MMSE domains were 1.14 (95% CI: 0.84–1.54), 1.50 (95% CI: 0.98–2.28), 2.14 (95% CI: 1.12–4.09) and 2.29 (95% CI: 1.24–5.04), respectively, and a dose-dependent relationship was significant (p for trend =0.003). Conclusion Cognitive impairment is associated with the increased risk of all-cause mortality in the Chinese elderly. Similarly, reduced MMSE scores, as well as impaired MMSE domains, are also associated with the increasing risk of all-cause mortality.
BackgroundTo explore the relationship between weight-adjusted-waist index (WWI) and the risk of all-cause mortality in one urban community-dwelling population in China.MethodsThis is a prospective cohort study with a sample of 1,863 older adults aged 60 years or over in Beijing who completed baseline examinations in 2009–2010 and a 10-year follow-up in 2020. WWI was calculated as waist circumference (cm) divided by the square root of weight (kg). Cox regression analysis was performed to investigate the significance of the association of WWI with all-cause mortality. The area under the receiver operating characteristic (ROC) curves were used to compare the ability of each obesity index to predict mortality.ResultsDuring a median follow-up of 10.8 years (1.0 to 11.3 years), 339 deaths occurred. After adjusted for covariates, the hazard ratios (HRs) for all-cause mortality progressively increased across the tertile of WWI. Compared with the lowest WWI category (tertile1 <10.68 cm/√kg), with WWI 10.68 to 11.24cm/√kg, and≥11.25 cm/√kg, the HRs (95% confidence intervals (CIs)) for all-cause mortality were 1.58 (1.12–2.22), and 2.66 (1.80–3.92), respectively. In stratified analyses, the relationship between WWI and the risk of all-cause mortality persisted. The area under ROC for WWI was higher for all-cause mortality than BMI, WHtR, and WC.ConclusionWWI was associated with a higher risk for all-cause mortality, and the association was more robust with the highest WWI category.
Cardiovascular disease (CVD) is a leading cause of death worldwide. Atherosclerosis is believed to be the major cause of CVD, characterized by atherosclerotic lesion formation and plaque disruption. Although remarkable advances in understanding the mechanisms of atherosclerosis have been made, the application of these theories is still limited in the prevention and treatment of atherosclerosis. Therefore, novel and effective strategies to treat high-risk patients with atherosclerosis require further development. Pigment epithelium-derived factor (PEDF), a glycoprotein with anti-inflammatory, anti-oxidant, anti-angiogenic, anti-thrombotic and anti-tumorigenic properties, is of considerable interest in the prevention of atherosclerosis. Accumulating research has suggested that PEDF exerts beneficial effects on atherosclerotic lesions and CVD patients. Our group, along with colleagues, has demonstrated that PEDF may be associated with acute coronary syndrome (ACS), and that the polymorphisms of rs8075977 of PEDF are correlated with coronary artery disease (CAD). Moreover, we have explored the anti-atherosclerosis mechanisms of PEDF, showing that oxidized-low density lipoprotein (ox-LDL) reduced PEDF concentrations through the upregulation of reactive oxygen species (ROS), and that D-4F can protect endothelial cells against ox-LDL-induced injury by preventing the downregulation of PEDF. Additionally, PEDF might alleviate endothelial injury by inhibiting the Wnt/β-catenin pathway. These data suggest that PEDF may be a novel therapeutic target for the treatment of atherosclerosis. In this review, we will summarize the role of PEDF in the development of atherosclerosis, focusing on endothelial dysfunction, inflammation, oxidative stress, angiogenesis and cell proliferation. We will also discuss its promising therapeutic implications for atherosclerosis.
N6-methyladenosine (m6A) is the most common and conserved internal eukaryotic mRNA modification. m6A modification is a dynamic and reversible post-transcriptional regulatory modification, initiated by methylase and removed by RNA demethylase. m6A-binding proteins recognise the m6A modification to regulate gene expression. Recent studies have shown that altered m6A levels and abnormal regulator expression are crucial in the ageing process and the occurrence of age-related diseases. In this review, we summarise some key findings in the field of m6A modification in the ageing process and age-related diseases, including cell senescence, autophagy, inflammation, oxidative stress, DNA damage, tumours, neurodegenerative diseases, diabetes, and cardiovascular diseases (CVDs). We focused on the biological function and potential molecular mechanisms of m6A RNA methylation in ageing and age-related disease progression. We believe that m6A modification may provide a new target for anti-ageing therapies.
Background In patients with diabetes and hypertension, proteinuria is independently associated with all-cause death. However, in the general population, urinary albumin to creatinine ratio (UACR) is less used to predict all-cause mortality. When the urinary albumin to creatinine ratio is within the normal range (UACR< 30 mg/g), the clinical relevance of an increased urinary albumin excretion rate is still debated. We studied the relationship between UACR and all-cause mortality in community populations, and compared UACR groups within the normal range. Methods The participants were the inhabitants from the Wanshoulu community in Beijing, China. The average age is 71.48 years, and the proportion of women is 60.1%. A total of 2148 people completed random urine samples to determine the urinary albumin to creatinine ratio (UACR). The subjects were divided into three groups according to UACR: Group 1 (UACR< 10 mg/g), Group 2 (10 mg/g < UACR< 30 mg/g), Group 3 (UACR> 30 mg/g). We used Kaplan-Meier survival analysis and Cox regression model to verify the relationship between UACR and all-cause mortality. Results At an average follow-up of 9.87 years (718,407.3 years), the total mortality rate were 183.4/1000. In the Cox proportional hazards model, after adjusting for possible confounders, those with normal high-value UACR (group 2) showed a higher all-cause mortality than those with normal low-value UACR (group 1) [hazard ratio (HR) 1.289, 95% confidence interval (CI) 1.002 ~ 1.659 for all-cause mortality]. Those with proteinuria (group 3) showed a higher all-cause mortality than those with normal low-value UACR (group 1) [hazard ratio (HR) 1.394, 95% confidence interval (CI) 1.020 ~ 1.905 for all-cause mortality]. Conclusion Urinary albumin to creatinine ratio is an important risk factor for all-cause death in community population. Even if it is within the normal range (UACR< 30 mg/g), it occurs in people with high normal value (10 mg/g < UACR< 30 mg/g), the risk of all-cause death will also increase.
The triglyceride glucose (TyG) index was regarded as a simple surrogate marker of insulin resistance (IR). It is confirmed that IR was significantly associated with hyperuricemia, and obesity was the risk factor for IR and hyperuricemia. However, the relationship between the TyG index and hyperuricemia and the potential role of obesity in Han Chinese hypertension are not entirely elucidated. A community‐based cross‐sectional study was conducted in 4551 hypertension patients aged 40–75 years with clinical and biochemical data. The TyG index was calculated as ln [fasting triglyceride (mg/dl) × fasting plasma glucose (mg/dl)/2]. Hyperuricemia was determined as serum uric acid ≥357μmol/L (6 mg/dl) for females and ≥417μmol/L (7 mg/dl) for males. Our study suggested that the TyG index was higher in patients with hyperuricemia than in those without (8.99±0.61, 8.70±0.59, p < .001). The prevalence of hyperuricemia in patients with the lowest (≤8.32), second (8.33–8.66), third (8.67–9.07) and the highest quartile (≥9.08) of the TyG index was 6.0%, 10.4%, 15.4%, 21.4%, respectively. Logistic regression analysis suggested that the higher quartile of TyG index was associated with increased hyperuricemia risk whether in crude or adjusted models ( p < .05). Mediation analysis showed that all of our obesity indexes partially mediated the association between the TyG index and hyperuricemia to some extent. In Conclusions, the TyG index is significantly associated with hyperuricemia in hypertension patients among Han Chinese, obesity plays a partial mediation role in this relationship.
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