Development of hypertension models for lung cancer screening cohorts using clinical and thoracic aorta imaging factors.

This study aims to develop and validate nomogram models utilizing clinical and thoracic aorta imaging factors to assess the risk of hypertension for lung cancer screening cohorts. We included 804 patients and collected baseline clinical data, biochemical indicators, coexisting conditions, and thoracic aorta factors. Patients were randomly divided into a training set (70%) and a validation set (30%). In the training set, variance, t-test/Mann-Whitney U-test and standard least absolute shrinkage and selection operator were used to select thoracic aorta imaging features for constructing the AIScore. Multivariate logistic backward stepwise regression was utilized to analyze the influencing factors of hypertension. Five prediction models (named AIMeasure model, BasicClinical model, TotalClinical model, AIBasicClinical model, AITotalClinical model) were constructed for practical clinical use, tailored to different data scenarios. Additionally, the performance of the models was evaluated using receiver operating characteristic (ROC) curves, calibration curves and decision curve analyses (DCA). The areas under the ROC curve for the five models were 0.73, 0.77, 0.83, 0.78, 0.84 in the training set, and 0.77, 0.78, 0.81, 0.78, 0.82 in the validation set, respectively. Furthermore, the calibration curves and DCAs of both sets performed well on accuracy and clinical practicality. The nomogram models for hypertension risk prediction demonstrate good predictive capability and clinical utility. These models can serve as effective tools for assessing hypertension risk, enabling timely non-pharmacological interventions to preempt or delay the future onset of hypertension.

The effects of palliative care on patients with different classes heart function: A pilot study.

The aim of this study was to explore effects of palliative care (PC) on patients with different heart function. Patients with NYHA (New York Heart Association) class II, III, IV were divided into separate groups. The KCCQ (Kansas City Cardiomyopathy Questionnaire) and HADS (Hospital Anxiety and Depression Scale) scores were compared before and 3 months after PC intervention. After 3 months, compared with the control group, PC could further significantly improve the KCCQ, HADS-depression and -anxiety scores of patients in NYHA class IV (P < 0.05); PC could significantly improve the HADS-depression and -anxiety scores of patients with NYHA class III (P < 0.05), and had an improvement tendency on KCCQ score. The study revealed that PC can significantly improve anxiety and depression of patients with NYHA class III or IV, and significantly improve the quality of life of patients with NYHA class IV, but had no effects on patients with NYHA class II.

Associations of serum calcium/magnesium ratios with coronary artery disease in diabetes: a cross-sectional study.

OBJECTIVE: The early detection of coronary artery disease (CAD) in diabetes mellitus is a major clinical difficulty. The purpose of this paper is to find out a convenient and economical index to help to screen for patients with CAD in diabetes mellitus. METHOD: From January 2019 to December 2019, a total of 1028 patients hospitalized in the general department of our hospital have been enrolled in our cross-sectional study, of which 190 were diagnosed with CAD and 314 with diabetes. Differences of various factors between the CAD group and the non-CAD group were analyzed. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the efficacy of each factor in predicting CAD. The correlation between calcium/magnesium (Ca/Mg) ratio and the prevalence of CAD in diabetic and non-diabetic people was compared, and the cutoff of Ca/Mg ratio to predict the risk of CAD in diabetic patients was calculated. RESULTS: Logistic regression analysis showed that serum high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, calcium, magnesium, Ca/Mg ratio, hypertension, diabetes, and smoking history were all associated with CAD. Among them, the AUC value of Ca/Mg ratio was the highest of 0.70. Furthermore, in diabetes patients, the AUC value of Ca/Mg ratio to predict the risk of CAD was 0.72, the cutoff was 2.55, the sensitivity was 77.1%, and the specificity was 53.7%. The prevalence rate of CAD was 18.5% below the cutoff, 46.9% higher than the cutoff, and the prevalence rate increased by 153.5%. CONCLUSION: The Ca/Mg ratio is a good predictor of the risk of CAD in diabetes, higher than the cutoff, the prevalence rate was significantly increased.PLA IN LANGUAGE SUMMARYCAD brings great pain and burden to patient. However, CAD is asymptomatic in quiet a few cases of type 2 diabetes until myocardial infarction or sudden cardiac death occurs. In this study, we explored the association between CAD and various serum factor. We found that the Ca/Mg ratio is of excellent value in screening CAD, especially in diabetes. Moreover, we found that the cutoff of Ca/Mg ratio was 2.55 in diabetic population and the prevalence rate of CAD was 18.5% below the cutoff, 46.9% higher than the cutoff. The Ca/Mg ratio will provide good prediction of the risk of CAD and make early detection easier in diabetes.

Opportunistic osteoporosis screening using chest CT with artificial intelligence.

Osteoporosis has a high incidence and a low detection rate. If it is not detected in time, it will cause osteoporotic fracture and other serious consequences. This study showed that the attenuation values of vertebrae on chest CT could be used for opportunistic screening of osteoporosis. This will be beneficial to improve the detection rate of osteoporosis and reduce the incidence of adverse events caused by osteoporosis. INTRODUCTION: To explore the value of the attenuation values of all thoracic vertebrae and the first lumbar vertebra measured by artificial intelligence on non-enhanced chest CT to do osteoporosis screening. METHODS: On base of images of chest CT, using artificial intelligence (AI) to measure the attenuation values (HU) of all thoracic and the first vertebrae of patients who underwent CT examination for lung cancer screening and dual-energy X-ray absorptiometry (DXA) examination during the same period. The patients were divided into three groups: normal group, osteopenia group, and osteoporosis group according to the results of DXA. Clinical baseline data and attenuation values were compared among the three groups. The correlation between attenuation values and BMD values was analyzed, and the predictive ability and diagnostic efficacy of attenuation values of thoracic and first lumbar vertebrae on osteopenia or osteoporosis risk were further evaluated. RESULTS: CT values of each thoracic vertebrae and the first lumbar vertebrae decreased with age, especially in menopausal women and presented high predictive ability and diagnostic efficacy for osteopenia or osteoporosis. After clinical data correction, with every 10 HU increase of CT values, the risk of osteopenia or osteoporosis decreased by 32 ~ 44% and 61 ~ 80%, respectively. And the combined diagnostic efficacy of all thoracic vertebrae was higher than that of a single vertebra. The AUC of recognizing osteopenia or osteoporosis from normal group was 0.831and 0.972, respectively. CONCLUSIONS: The routine chest CT with AI is of great value in opportunistic screening for osteopenia or osteoporosis, which can quickly screen the population at high risk of osteoporosis without increasing radiation dose, thus reducing the incidence of osteoporotic fracture.

Cross-sectional association between body fat percentage and arteriosclerosis assessed by Cardio-Ankle Vascular Index in a Chinese population: a retrospective observational study.

OBJECTIVE: To evaluate arteriosclerosis using Cardio-Ankle Vascular Index (CAVI) and to explore the relation between the body fat percentage (BFP) and CAVI. DESIGN: A retrospective observational study. SETTING AND PARTICIPANTS: A total of 1152 patients admitted to a geriatric unit and general practice at a mega hospital in Wuhan, China, from November 2018 to November 2019 were included in this study. PRIMARY OUTCOME: Association between BFP and CAVI. RESULTS: Multiple linear regression analysis showed that BFP was positively correlated with CAVI after correction for potential confounding variables (ß=0.03; 95% CI: 0.01 to 0.05); this association persisted after BFP was treated by quartile categorical variables and the trend test was statistically significant (p for trend=0.002). Meanwhile, the generalised additive model showed a non-linear association between BFP and CAVI. When BFP<20.6%, BFP is not associated with CAVI for (ß=-0.02; 95% CI: -0.06 to 0.03), but when BFP≥20.6%, there is a linear positive association between BFP and CAVI (ß=0.05; 95% CI: 0.02 to 0.07). Subgroup analysis showed that there was an interaction between BFP and CAVI in the age stratification (p interaction=0.038). CONCLUSION: BFP was non-linearly correlated with CAVI, with a 0.05 increase in CAVI for every 1% increase in BFP when BFP≥20.6% and a 0.03 increase in CAVI in those >65 years of age.

Artificial intelligence measuring the aortic diameter assist in identifying adverse blood pressure status including masked hypertension.

INTRODUCTION AND OBJECTIVES: Artificial intelligence (AI) made it achievable that aortic dilation could be measured in CT images indirectly, while aortic diameter (AD) has the certain relationship with blood pressure. It was potential that the blood pressure condition be determined by AD measurement using the data obtained from a CT scanning especially in identifying masked hypertension and predicting the risk of poor control of blood pressure (BP) which was easy to elude diagnosis in clinic. We aimed to evaluate the possibility of utilizing AD by AI for predicting the risk of adverse BP status (including masked hypertension or poor BP control) and the optimal thoracic aortic position in measurement as well as the cutoff value for predicting the risk. METHODS: Eight hundred and one patients were enrolled in our study. AI-Rad Companion Cardiovascular (K183268 FDA approved) was used to perform automatic aorta measurement in thoracic CT images at nine key positions based on AHA guidelines. Data was post processed by software from AI-Rad Companion undergone rigorous clinical validation by both FDA and CE as verification of its efficacy and usability. The AD's risk and diagnostic value was assessed in identifying hypertension in the general population, in identifying the poor BP controlled in the hypertension population, and in screening masked hypertension in the general population respectively by multiple regression analysis and receiver operating curve analysis. RESULTS: AD measured by AI was a risk factor for adverse BP status after clinical covariates adjustment (OR = 1.02 ~ 1.26). The AD at mid descending aorta was mostly affected by BP particularly, which is optimal indicator in identifying hypertension in the general population (AUC = 0.73) and for screening masked hypertension (AUC = 0.78). CONCLUSION: Using AI to measure the AD of the aorta, particularly at the position of mid descending aorta, is greatly valuable for identifying people with poor BP status. It will be possible to reveal more clinical information reflected by ordinary CT images and enrich the screening methods for hypertension, especially masked hypertension.PLAIN LANGUAGE SUMMARYHTN has a significant adverse effect on arterial deformation. BP and arterial dilation promote each other in a vicious circle. Arterial dilation may not be restricted by apparent fluctuations in BP and is objective evidence of an undesirable BP state. The accuracy of AD measurements by AI on chest CT images has been verified. There has not been the application of AD measurement by AI in the scene of poor BP status in clinical practice.In this study, we applied AI to measure the diameter of the aorta in nine consecutive positions. We explored the association between AD at various positions and BP levels and the possibility that AD in identifying poor BP status in different populations. We found that the AD at the MD is of great value in screening MH and evaluating the control state of BP in HTN. It will be possible to significantly expand the clinical information reflected by ordinary CT images and enrich the screening methods for HTN, especially MH.

The Leukocyte Subtype Counts and Ratios Can Effectively Predict the Risk of Arterial Stiffness Assessed by Cardio-Ankle Vascular Index: A Retrospective Study.

Background: Arterial stiffness was the pathological basis and risk factor of cardiovascular diseases, with chronic inflammation as the core characteristic. We aimed to analyze the association between the arterial stiffness measured by cardio-ankle vascular index (CAVI) and indicators reflecting the inflammation degree, such as count of leukocyte subtypes, platelet, and monocyte-to-lymphocyte ratio (MLR), etc. Methods: The data of inpatients from November 2018 to November 2019 and from December 2019 to September 2020 were continuously collected as the training set (1,089 cases) and the validation set (700 cases), respectively. A retrospective analysis of gender subgroups was performed in the training set. The association between inflammatory indicators and CAVI or arterial stiffness by simple linear regression, multiple linear regression, and logistic regression was analyzed. The effectiveness of the inflammation indicators and the CAVI decision models to identify arterial stiffness by receiver operating curve (ROC) in the training and validation set was evaluated. Results: The effect weights of MLR affecting the CAVI were 12.87% in men. MLR was the highest risk factor for arterial stiffness, with the odds ratio (95% confidence interval) of 8.95 (5.04-184.79) in men after adjusting the covariates. A cutpoint MLR of 0.19 had 70% accuracy for identifying arterial stiffness in all participants. The areas under the ROC curve of the CAVI decision models for arterial stiffness were >0.80 in the training set and validation set. Conclusions: The MLR might be a high-risk factor for arterial stiffness and could be considered as a potential indicator to predict arterial stiffness.

Associations between bone mineral density in different measurement locations and coronary artery disease: a cross-sectional study.

The bone mineral density (BMD) loss is closely related to coronary heart disease (CAD). The BMD measured at different locations differ in BMD values, the risk to CAD, and the capability to identify CAD. An average BMD of the right and left femoral neck being below - 1.70 has the ability to indicate risk of CAD. PURPOSE: Previous studies have reported that low bone mineral density (BMD) is closely related to coronary artery disease (CAD); however, it is not clear that the BMD loss at which location to what extent has the greatest effect in identifying risk of CAD. This study aimed to evaluate the ability of different measurement sites of BMD in identifying CAD and analyze the best measurement sites and the optimal cut-off of BMD for CAD. METHODS: This was a cross-sectional study in which 180 of 817 participants were diagnosed with CAD. All participants in the study were measured by dual-energy X-ray absorptiometry (DEXA) for BMD at 8 locations, and following measurements were derived: the average BMD of lumbar spine (L1-L4), femoral neck (left and right), and total proximal femur (left and right). The association between BMD at different locations and CAD was analyzed using logistic regression. The receiver operating characteristic (ROC) curve was used to select the optimal measurement location and cut-off value of the BMD for identifying CAD. RESULTS: There were significant differences in BMD at 3 different measurement locations. Higher BMD is a protective factor against CAD, which is more pronounced in the femoral neck and total proximal femur (ORs = 0.47 ~ 0.66, P < 0.001) than in the lumbar spine (ORs = 0.74 ~ 0.79, P < 0.001). The optimal site for predicting the risk of CAD by BMD is the femoral neck, with the AUC (area under the ROC curve) is 0.72 (95% CI: 0.67 ~ 0.76) and the cut-off is - 1.70. CONCLUSION: The BMD below particular cut-off of the femoral neck rather than of the lumbar spine may have certain further research value for revealing the risk of CAD.

Redd1 knockdown prevents doxorubicin-induced cardiac senescence.

Regulated in development and DNA damage response-1 (Redd1) is a stress-response gene that is transcriptionally induced by diverse stressful stimuli to influence cellular growth and survival. Although evidence suggests that aging may drive Redd1 expression in skeletal muscles, the expression patterns and functions of Redd1 in senescent cardiomyocytes remain unspecified. To address this issue, in vitro and in vivo models of cardiomyocyte senescence were established by administration of doxorubicin (Dox). Redd1 overexpression and knockdown was achieved in cultured H9c2 cardiomyocytes and mouse tissues using, respectively, lentivirals and adeno-associated virus 9 (AAV9) vectors. In the hearts of both aged (24 months old) and Dox-treated mice, as well as in Dox-exposed H9c2 cardiomyocytes, high Redd1 expression accompanied the increase in both cellular senescence markers (p16INK4a and p21) and pro-inflammatory cytokine expression indicative of a stress-associated secretory phenotype (SASP). Notably, Redd1 overexpression accentuated, whereas Redd1 silencing markedly attenuated, Dox-induced cardiomyocyte senescence features both in vitro and in vivo. Notably, AAV9-shRNA-mediated Redd1 silencing significantly alleviated Dox-induced cardiac dysfunction. Moreover, through pharmacological inhibition, immunofluorescence, and western blotting, signaling pathway analyses indicated that Redd1 promotes cardiomyocyte senescence as a downstream effector of p38 MAPK to promote NF-kB signaling via p65 phosphorylation and nuclear translocation.

MicroRNA-126 enhances the biological function of endothelial progenitor cells under oxidative stress via PI3K/Akt/GSK3ß and ERK1/2 signaling pathways.

Endothelial progenitor cell (EPC) transplantation is a safe and effective method to treat acute myocardial infarction (AMI). However, oxidative stress leads to the death of a large number of EPCs in the early stage of transplantation, severely weakening the therapeutic effect. Previous studies demonstrated that microRNAs regulate the biological function of EPCs. The aim of the current study was to investigate the effect of microRNA on the biological function of EPCs under oxidative stress. Quantitative reverse transcription PCR was performed to detect the expression of miR-126, miR-508-5p, miR-150, and miR-16 in EPCs from rats, among which miR-126 showed a relatively higher expression. Treatment with H2O2 decreased miR-126 expression in EPCs in a dose-dependent manner. EPCs were further transfected with miR-126 mimics or inhibitors, followed by H2O2 treatment. Overexpression of miR-126 enhanced the proliferation, migration, and tube formation of H2O2-treated EPCs. MiR-126 overexpression also inhibited reactive oxygen species and malondialdehyde levels and enhanced superoxide dismutase levels, as well as increased angiopoietin (Ang)1 expression and decreased Ang2 expression in H2O2-treated EPCs. Moreover, miR-126 participated in the regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3ß (GSK3ß) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in EPCs, where both pathways were activated after miR-126 overexpression in H2O2-treated EPCs. Overall, we showed that miR-126 promoted the biological function of EPCs under H2O2-induced oxidative stress by activating the PI3K/Akt/GSK3ß and ERK1/2 signaling pathway, which may serve as a new therapeutic approach to treat AMI.

Thoracic Aorta Diameter Calculation by Artificial Intelligence Can Predict the Degree of Arterial Stiffness.

Background: Arterial aging is characterized by decreased vascular function, caused by arterial stiffness (AS), and vascular morphological changes, caused by arterial dilatation. We analyzed the relationship of pre-AS and AS, as assessed by cardio ankle vascular index (CAVI), with arterial diameters (AD) at nine levels, from the aortic sinus to the abdominal aorta, as measured by artificial intelligence (AI) on non-enhanced chest computed tomography (CT) images. Methods: Overall, 801 patients who underwent both chest CT scan and arterial elasticity test were enrolled. Nine horizontal diameters of the thoracic aorta (from the aortic sinuses of Valsalva to the abdominal aorta at the celiac axis origin) were measured by AI using CT. Patients were divided into non-AS (mean value of the left and right CAVIs [M.CAVI] < 8), pre-AS (8 ≤ M.CAVI < 9), and AS (M.CAVI ≥ 9) groups. We compared AD differences among groups, analyzed the correlation of age, ADs, and M.CAVI or the mean pressure-independent CAVI (M.CAVI0), Furthermore, we evaluated the risk predictors and the diagnostic value of the nine ADs for pre-AS and AS. Results: The AD at mid descending aorta (MD) correlated strongest with CAVI (r = 0.46, p < 0.001) or M.CAVI0 (r = 0.42, p < 0.001). M.CAVI was most affected by the MD AD and by age. An increase in the MD AD independently predicted the occurrence of pre-AS or AS. For MD AD, every 4.37 mm increase caused a 14% increase in the pre-AS and AS risk and a 13% increase in the AS risk. With a cut-off value of 26.95 mm for the MD AD, the area under the curve (AUC) for identifying the risk of AS was 0.743. With a cut-off value of 25.15 mm, the AUC for identifying the risk of the stage after the prophase of AS is 0.739. Conclusions: Aging is associated with an increase in AD and a decrease in arterial elasticity. An increase in AD, particularly at the MD level is an independent predictor of AS development.

Honokiol antagonizes doxorubicin­induced cardiomyocyte senescence by inhibiting TXNIP­mediated NLRP3 inflammasome activation.

Senescence of cardiomyocytes is considered a key factor for the occurrence of doxorubicin (Dox)­associated cardiomyopathy. The NOD­like receptor family pyrin domain­containing 3 (NLRP3) inflammasome is reported to be involved in the process of cellular senescence. Furthermore, thioredoxin­interactive protein (TXNIP) is required for NLRP3 inflammasome activation and is considered to be a key component in the regulation of the pathogenesis of senescence. Studies have demonstrated that pretreatment with honokiol (Hnk) can alleviate Dox­induced cardiotoxicity. However, the impact of Hnk on cardiomyocyte senescence elicited by Dox and the underlying mechanisms remain unclear. The present study demonstrated that Hnk was able to prevent Dox­induced senescence of H9c2 cardiomyocytes, indicated by decreased senescence­associated ß­galactosidase (SA­ß­gal) staining, as well as decreased expression of p16INK4A and p21. Hnk also inhibited TXNIP expression and NLRP3 inflammasome activation in Dox­stimulated H9c2 cardiomyocytes. When TXNIP expression was enforced by adenovirus­mediated gene overexpression, the NLRP3 inflammasome was activated, which led to inhibition of the anti­inflammation and anti­senescence effects of Hnk on H9c2 cardiomyocytes under Dox treatment. Furthermore, adenovirus­mediated TXNIP­silencing inhibited the NLRP3 inflammasome. Consistently, TXNIP knockdown enhanced the anti­inflammation and anti­senescence effects of Hnk on H9c2 cardiomyocytes under Dox stimulation. In summary, Hnk was found to be effective in protecting cardiomyocytes against Dox­stimulated senescence. This protective effect was mediated via the inhibition of TXNIP expression and the subsequent suppression of the NLRP3 inflammasome. These results demonstrated that Hnk may be of value as a cardioprotective drug by inhibiting cardiomyocyte senescence.

Redd1 protects against post­infarction cardiac dysfunction by targeting apoptosis and autophagy.

Post­infarction remodeling is accompanied and influenced by perturbations in the mammalian target of rapamycin (mTOR) signaling. Regulated in development and DNA damage response­1 (Redd1) has been reported to be involved in DNA repair and modulation of mTOR activity. However, little is known about the role of Redd1 in the heart. In the present study the potential contribution of Redd1 overexpression to the chronic phase of heart failure after myocardial infarction (MI) was explored and the mechanisms underlying Redd1 actions were determined. Redd1 was downregulated in the mouse heart subjected to MI surgery. To determine the role of Redd1 in the process of MI, adeno­associated virus 9 mediated overexpression of Redd1 was used to enhance Redd1 content in cardiomyocytes. Redd1 overexpression improved left ventricular dysfunction and reduced the expansion index. Additionally, Redd1 overexpression resulted in suppressed myocardial apoptosis and improved autophagy. Furthermore, the studies revealed that Redd1 overexpression could inhibit the phosphorylation of mTOR and its downstream effectors P70/S6 kinase and 4EBP1. In conclusion, this study demonstrated that Redd1 overexpression protects against the development and persistence of heart failure post MI by reducing apoptosis and enhancing autophagy via the mTOR signaling pathway. The present study clearly demonstrated that Redd1 is a therapeutic target in the development of heart failure after MI.

Reduced NRF2 expression suppresses endothelial progenitor cell function and induces senescence during aging.

Aging is associated with an increased risk of cardiovascular disease. Numerical and functional declines in endothelial progenitor cells (EPCs) limit their capacity for endothelial repair and promote the development of cardiovascular disease. We explored the effects of nuclear factor (erythroid-derived 2)-like 2 (NRF2) on EPC activity during aging. Both in vitro and in vivo, the biological functioning of EPCs decreased with aging. The expression of NRF2 and its target genes (Ho-1, Nqo-1 and Trx) also declined with aging, while Nod-like receptor protein 3 (NLRP3) expression increased. Aging was associated with oxidative stress, as evidenced by increased reactive oxygen species and malondialdehyde levels and reduced superoxide dismutase activity. Nrf2 silencing impaired the functioning of EPCs and induced oxidative stress in EPCs from young mice. On the other hand, NRF2 activation in EPCs from aged mice protected these cells against oxidative stress, ameliorated their biological dysfunction and downregulated the NLRP3 inflammasome. These findings suggest NRF2 can prevent the functional damage of EPCs and downregulate the NLRP3 inflammasome through NF-κB signaling.

Prognostic Value of Neutrophil to Lymphocyte Ratio for In-hospital Mortality in Elderly Patients with Acute Myocardial Infarction.

Coronary artery disease (CAD) is a multifactorial disease in which inflammation plays a central role. This study aimed to investigate the association of inflammatory markers such as the neutrophil to lymphocyte ratio (NLR), the Global Registry of Acute Coronary Events (GRACE) score with in-hospital mortality of elderly patients with acute myocardial infarction (AMI) in an attempt to explore the prognostic value of these indices for elderly AMI patients. One thousand consecutive CAD patients were divided into two groups based on age 60. The laboratory and clinical characteristics were assessed retrospectively by reviewing the medical records. The NLR and GRACE score were calculated. In the elderly (≥60 years), patients with non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI) had significantly higher NLR than did those with unstable angina (UA) and stable angina pectoris (SAP) (P<0.01). The NLR was considerably elevated in older AMI patients compared with their younger counterparts (<60 years) (P<0.05). In elderly AMI patients, the NLR was considerably higher in the high-risk group than in both the low-risk and medium-risk groups based on the GRACE score (P<0.05 and P<0.01, respectively), and the NLR was positively correlated with the GRACE score (r=0.322, P<0.001). Either the NLR level or the GRACE score was significantly higher in the death group than in the surviving group (P<0.05). By curve receiver operator characteristic curve (ROC) analysis, the optimal cut-off levels of 9.41 for NLR and 174 for GRACE score predicted in-hospital death [ROC area under the curve (AUC) 0.771 and 0.787, respectively, P<0.001]. It was concluded that an elevated NLR is a potential predictor of in-hospital mortality in elderly patients with AMI.

Nrf2 protects against diabetic dysfunction of endothelial progenitor cells via regulating cell senescence.

Diabetes is associated with an increased risk of cardiovascular disease. A decrease in the number and functionality of endothelial progenitor cells (EPCs) leads to reduced endothelial repair and the development of cardiovascular disease. The aim of the present study was to explore the effect and underlying mechanisms of nuclear factor erythroid 2­related factor 2 (Nrf2) on EPC dysfunction caused by diabetic mellitus. The biological functions of EPCs in streptozotocin­induced diabetic mice were evaluated, including migration, proliferation, angiogenesis and the secretion of vascular endothelial growth factor (VEGF), stromal­derived growth factor (SDF) and nitric oxide (NO). Oxidative stress levels in diabetic EPCs were also assessed by detecting intracellular reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA). EPC senescence was evaluated by measuring p16 and b­gal expression and observing the senescence­associated secretory phenotype. In addition, the function of EPCs and level of oxidative stress were assessed following Nrf2 silencing or activation. Nrf2 silencing resulted in a decrease of EPC biological functions, accelerated cell senescence and increased oxidative stress, as indicated by ROS and MDA upregulation accompanied with decreased SOD activity. Furthermore, Nrf2 silencing inhibited migration, proliferation and secretion in EPCs, while it increased oxidative stress and cell senescence. Nrf2 activation protected diabetic EPCs against the effects of oxidative stress and cell senescence, ameliorating the biological dysfunction of EPCs derived from mice with diabetes. In conclusion, Nrf2 overexpression protected against oxidative stress­induced functional damage in EPCs derived from diabetic mice by regulating cell senescence.

Hypoxic Preconditioning Enhances Biological Function of Endothelial Progenitor Cells via Notch-Jagged1 Signaling Pathway.

BACKGROUND Hypoxic preconditioning may be a key influence on functions of endothelial progenitor cells (EPCs). MATERIAL AND METHODS To investigate the role and mechanism of the Notch-Jagged1 pathway on endothelial progenitor cells in hypoxic preconditioning, endothelial progenitor cells were randomly allocated into 5 groups: 1 Normoxic control group; 2 Hypoxic blank group; 3 Hypoxic+25 µM DAPT group; 4 Hypoxic+50 µM DAPT group; 5 Hypoxic+100 µM DAPT group. After reoxygenation, protein and mRNA levels of Jagged1 were measured by Western blot and quantitative RT-PCR. The MTT test was used to assess proliferation. ELISA was used to measure NO and VEGF secretion. RESULTS Hypoxic preconditioning treatment significantly upregulated both protein and mRNA levels of Jagged1 in endothelial progenitor cells. It also enhanced proliferation ability and elevated secretion of NO and VEGF. Furthermore, after blocking the Notch pathway by using DAPT, Jagged1 expression and EP proliferation, migration, and secretion of NO and VEGF were decreased in a dose-dependent manner. CONCLUSIONS Our results suggest the Notch-Jagged1 pathway enhances EPCs proliferation and secretion ability during hypoxic preconditioning.

Cloning and functional analysis of human acyl coenzyme A: Cholesterol acyltransferase1 gene P1 promoter.

Acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1) catalyzes the conversion of free cholesterol (FC) to cholesterol ester. The human ACAT1 gene P1 promoter has been cloned. However, the activity and specificity of the ACAT1 gene P1 promoter in diverse cell types remains unclear. The P1 promoter fragment was digested with KpnI/XhoI from a P1 promoter cloning vector, and was subcloned into the multiple cloning site of the Firefly luciferase vector pGL3­Enhancer to obtain the construct P1E­1. According to the analysis of biological information, the P1E­1 plasmid was used to generate deletions of the ACAT1 gene P1 promoter with varying 5' ends and an identical 3' end at +65 by polymerase chain reaction (PCR). All the 5'­deletion constructs of the P1 promoter were identified by PCR, restriction enzyme digestion mapping and DNA sequencing. The transcriptional activity of each construct was detected after transient transfection into THP­1, HepG2, HEK293 and Hela cells using DEAE­dextran and Lipofectamine 2000 liposome transfection reagent. Results showed that the transcriptional activity of the ACAT1 gene P1 promoter and deletions of P1 promoter in THP­1 and HepG2 cells was higher than that in HEK293 and HeLa cells. Moreover, the transcriptional activity of P1E­9 was higher compared with those of other deletions in THP­1, HepG2, HEK293 and HeLa cells. These findings indicate that the transcriptional activity of the P1 promoter and the effects of deletions vary with different cell lines. Thus, the P1 promoter may drive ACAT1 gene expression with cell­type specificity. In addition, the core sequence of ACAT1 gene P1 promoter was suggested to be between -125 and +65 bp.

Chlamydia pneumoniae disrupts lipid metabolism in human umbilical vein endothelial cells.

Atherosclerosis is well established as a chronic inflammatory disorder, and Chlamydia pneumoniae is considered to be a risk factor for atherosclerotic development. Endothelial dysfunction, caused by oxidized low­density lipoprotein (ox­LDL) is an early atherosclerotic marker. However, the effect of C. pneumoniae on lipid metabolism in vascular endothelial cells is yet to be elucidated. The aim of the present study was to investigate the effects of C. pneumoniae on lipid metabolism in human umbilical vein endothelial cells (HUVECs). In the present study, LDL oxidation was found to be significantly induced in the supernatant, but not the cell lysates, of C. pneumoniae­infected HUVECs. Furthermore, C. pneumoniae infection was observed to increase the levels of total cholesterol and cholesteryl esters in LDL­treated HUVECs. In addition, C. pneumoniae was found to upregulate the expression of scavenger receptor A, cluster of differentiation 36 and acyl­coenzyme A: cholesterol acyltransferase 1 mRNA and protein. C. pneumoniae was also observed to downregulate the mRNA and protein expression of ATP binding cassette transporter (ABC) A1 and ABCGl in LDL­treated HUVECs. These results show that C. pneumoniae disrupts lipid metabolism in HUVECs.

Nicorandil attenuates endothelial VCAM-1 expression via thioredoxin production in diabetic rats induced by streptozotocin.

The anti-angina agent nicorandil has been reported to be beneficial even in patients who have angina with diabetes. However, the mechanism underlying the effect of nicorandil in patients with diabetes remains to be elucidated. In this study, the protective effect of nicorandil on thioredoxin (TRX) protein was investigated, as TRX is a multifunctional endogenous redox regulator that protects cells against various types of cellular and tissue stress. This study was conducted to examine whether nicorandil induces the expression of TRX for the protection against diabetic damage in the vascular tissue of rats. Diabetes was induced in rats by intraperitoneal injection of streptozotocin (STZ) (fasting glucose levels in STZ-induced rats were >14 mmol/l). Diabetic rats were divided into a diabetic control and a nicorandil-treated group. Nicorandil was administered at a dosage of 15 mg/kg/day by gavage feeding. After five weeks of nicorandil administration, blood samples were obtained from the angular vein to measure levels of stress markers, serum superoxide dismutase and malondialdehyde, using the ELISA. The expression of TRX in STZ-induced rat vascular tissue was analyzed by immunohistochemistry, quantitative polymerase chain reaction (qPCR) and western blot analysis. The oral administration of nicorandil induced TRX protein and mRNA expression in the vascular tissue of STZ-induced diabetic rats. In the diabetic control group, the levels of stress were markedly higher than those in the nicorandil-treated group, indicating that nicorandil reduces oxidative stress in serum. In addition to inducing TRX expression, nicorandil attenuated the expression of the vascular cell adhesion molecule-1 (VCAM-1) in diabetic rat vascular endothelial cells. In conclusion, nicorandil attenuates the formation of reactive oxygen species and induces TRX protein expression, consequently resulting in the suppression of VCAM-1 secretion in the vascular endothelial cells of STZ-induced diabetic rats.