BackgroundIn centenarian populations, application of the positive biology approach (examination of positive phenotypes in aging) has revealed that mitochondrial DNA (mtDNA) mutation accumulation may be linked to human longevity; however, the role of guanine nucleotide-binding protein (G protein) abnormalities modulated by G-protein beta-3 (GNB3) and nitrate (NO2) production associated with endothelial nitric oxide synthase (eNOS), commonly appearing in age-related diseases, remains undetermined.ObjectiveThe association between the mtDNA 5178A/C, mtDNA 10398A/G, GNB3 C825T, and eNOS polymorphisms and longevity in a Uygur population (Xinjiang region, China) were investigated.MethodsA total of 275 experimental subjects aged ≥100 or with 4 generations currently living were screened for inclusion in the centenarian (>100 years) and nonagenarian groups (90–100 years), and 112 65–70 year old control subjects were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine mtDNA 5178A/C, mtDNA 10398A/G, GNB3 C825T, and eNOS. Associations between polymorphic loci, genotypes, and longevity were analyzed.Results165 included subjects (M∶F = 107∶58; mean age = 97±3 years; mean age 100–113 years) were assigned to the centenarian (M∶F = 46/19; n = 65) and nonagenarian groups (M∶F = 61/39; n = 100). Associations between mtDNA C5178A and A10398G polymorphisms with longevity in the centenarian group with mtDNA genotype frequencies 5178A and 10398G were 66.79% and 36.8%.ConclusionsApplying the overwhelming longevity observed in Uygur populations, these findings demonstrate that mtDNA 5178A/C and 10398A/G, GNB3 C825T, and eNOS polymorphisms are useful as a genetic basis for longevity.

Background: Mounting evidence suggests that endothelial cell-derived microparticles (EMPs) and red blood cell-derived microparticles (RMPs), which have procoagulant and vasoconstriction effects, are involved in the development of vascular acute cardiovascular events. The aim of this study was to analyze the circulating levels of EMPs and RMPs in patients with acute myocardial infarction (AMI), and to explore the correlations between EMPs and RMPs and the severity of coronary artery disease.Methods: Plasma samples from 110 patients with AMI and 57 non-coronary artery disease group (non-CAD) were collected in the present study. The flow cytometry was used to measure the EMPs (CD31) and RMPs (CD235a) qualitatively and quantitatively.Results: The levels of EMPs and RMPs in the AMI group were higher than that in the Non-CAD group, yet no significant difference was found between STEMI and non-STEMI subjects. The levels of EMPs and RMPs in multi-vessel were higher than in the single-vessel l disease. In the Thrombolysis in Myocardial Infarction (TIMI) risk assessment, the levels of EMPs in the high-risk group were higher than that in both intermediate-and low-risk group. The low-risk group had the lowest EMP levels, the difference between the groups being statistically significant (P=0.001). No significant difference in RMP levels was noted upon TIMI stratification. According to the ROC curve analysis, the areas under the curve (AUC) of EMPs and RMPs were 0.706 and 0.668, respectively. Conclusions:The circulating levels of EMPs and RMPs in patients with AMI are elevated, and the level of EMPs is related to the degree of coronary artery disease and the prognosis risk. The EMPs are more likely to be potential biomarkers than RMPs to provide diagnostic value for AMI.

Background Little is known about the predictive value of soluble AXL (sAXL) in heart failure (HF). This study aimed to describe the prognostic value of plasma sAXL in patients with symptomatic HF. Methods This is a multicentre observational prospective cohort study (Registration No. NCT03727828). Plasma sAXL were measured on admission. The primary endpoint is a composite of cardiovascular mortality and HF rehospitalization. Associations between plasma sAXL levels and clinical endpoints are described using Cox regression models and Kaplan–Meier methods. Results A total of 1030 symptomatic HF patients were enrolled in the study; the mean age (65% men) was 71 ± 12 years, with a median follow‐up of 32 months (IQR: 26–41 months). The mean baseline sAXL levels were 20.03 ± 6.74 ng/mL. Plasma sAXL positively associated with NYHA classification and negatively associated with left ventricular ejection fraction (both P < 0.001). Cox regression showed that 1‐SD increment of sAXL was associated with primary endpoint [HR (CI): 1.128 (1.024–1.242)], cardiovascular mortality [1.112 (1.032–1.198)], all‐cause mortality [1.142 (1.057–1.234)], and HF rehospitalization [1.122 (1.030–1.224)] after adjustment for potential confounders including NT‐proBNP. Kaplan–Meier curves revealed that patients with the highest sAXL levels were at the highest risk of primary endpoint events, cardiovascular mortality, and all‐cause mortality (all P values < 0.001). Furthermore, both Kaplan–Meier method and Categorical analysis demonstrated that the combined use of sAXL and NT‐proBNP were more likely to predict all‐cause or cardiovascular mortality (both P < 0.001). Similar results were observed when separating patients with respect to left ventricular ejection fraction, namely, in HFrEF, HFmrEF, and HFpEF groups. Conclusions Plasma sAXL concentrations are of great importance in predicting clinical outcomes in HF patients, independent of NT‐proBNP, suggesting that sAXL is a promising prognostic marker for further study.

ObjectiveTo explore the sociodemographic patterning of risk factors for cardiovascular disease (CVD) in three isolated-based subgroups of the Uyghur population in Xinjiang, China.DesignA cross-sectional study. Between 2005 and 2008, a non-probability sampling design method was used to select three specific groups of the Uyghur rural populations based on their potential socioeconomic status (ie, isolated, semi-isolated and open-environment status).SettingThree communities (named Desert, Turpan and Yuli Rob) in Southern Xinjiang autonomous region, China.Participants1656 people were included in this study. The inclusion criteria were that all participants were 18 years or older, they were descendants of at least three generations living in the same region, and there was no history of intermarriage.Main outcome measuresThe prevalence of CVD risk factors (ie, tobacco use, alcohol use, obesity, dyslipidemia, hypertension, diabetes, etc) was assessed.ResultsCompared with the Desert and Turpan communities, Yuli Rob had the highest levels of obesity, dyslipidemia and hypertension, and the Desert had the lowest levels of CVD risk factors. Age standardisation slightly altered the estimates, though the patterns remained unchanged. Some unique characteristics were also found. For example, the Desert group displayed significantly lower high-density lipoprotein cholesterol (HDLC) level compared with Yuli Rob and Turpan groups. The mean values were 0.63, 1.06 and 1.45 mmol/l for men and 0.64, 1.22 and 1.51 mmol/l for women (p<0.0001). The HDLC levels in the Desert group increased with increase in body mass index and fasting glucose levels, which was inconsistent with previous studies.ConclusionsIdentifying the unique CVD risk factors of the ethnic-specific populations is very important in development of tailored strategies for the prevention of CVD.

IntroductionInterleukin (IL)-33 was previously shown to induce angiogenesis and inflammatory activation of endothelial Microparticles(EMPs). Tissue factor (TF) plays a central role in hemostasis and thrombosis.Material and methodsThe study analyzed the coronary blood of level of CD31+EMPs, TF protein and IL-33 protein in Acute Myocardial Infarction (AMI) and stable coronary artery disease (SCAD) patients. Human coronary artery endothelial cells (HCAECs) were treated with IL-33 to obtain EMPs. The TF activity of EMPs was tested by Thermo Fisher by adding the TF antibody. Furthermore, TF and Tissue Factor Pathway Inhibitor (TFPI) protein were tested by ELISA. Finally, NF-κB inhibitor dimethyl fumarate (DMF) and soluble extracellular domain of ST2 coupled to the Fc fragment of human IgG1 (sST2) were added to HCAECs which were treated with IL-33, and the TF protein level was also tested by ELISA.ResultsThe AMI patients had higher level of CD31+EMPs, TF protein and IL-33 protein than the SCAD patients in coronary artery. In AMI patients (N=27), the IL-33 protein positively correlated with CD31+EMPs (r=0.794, p<0.01). According to the ROC curve analysis, the AUC of CD31+EMPs, TF protein and IL-33 protein were 0.888, 0.962 and 0.778 respectively. In the cell culture, the TF activity and TF protein in EMPs increased gradually with time of intervention by the treatment of IL-33. IL-33 binding to the ST2 receptor promoted TF expression by regulating NF-κB activation in EMPs of HCAECs.ConclusionsActivated endothelial cells and EMPs they released simultaneously express TF, which is a risk factor for cardiovascular disease.