Dongxue Dai

Visceral Adiposity Index and Lipid Accumulation Product Index: Two Alternate Body Indices to Identify Chronic Kidney Disease among the Rural Population in Northeast China

We aimed to compare the relative strength of the association between anthropometric obesity indices and chronic kidney disease (CKD). Another objective was to examine whether the visceral adiposity index (VAI) and lipid accumulation product index (LAPI) can identify CKD in the rural population of China. There were 5168 males and 6024 females involved in this cross-sectional study, and 237 participants (2.12%) suffered from CKD. Obesity indices included body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), VAI and LAPI. VAI and LAPI were calculated with triglyceride (TG), high-density lipoprotein (HDL), BMI and WC. VAI = [WC/39.68 + (1.88 × BMI)] × (TG /1.03) × (1.31/ HDL) for males; VAI = [WC/36.58 + (1.89 × BMI)] × (TG/0.81) × (1.52/HDL) for females. LAPI = (WC-65) × TG for males, LAPI = (WC-58) × TG for females. CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m2. The prevalence of CKD increased across quartiles for WHtR, VAI and LAPI. A multivariate logistic regression analysis of the presence of CKD for the highest quartile vs. the lowest quartile of each anthropometric measure showed that the VAI was the best predictor of CKD in females (OR: 4.21, 95% CI: 2.09–8.47, p < 0.001). VAI showed the highest AUC for CKD (AUC: 0.68, 95% CI: 0.65–0.72) and LAPI came second (AUC: 0.66, 95% CI: 0.61–0.70) in females compared with BMI (both p-values < 0.001). However, compared with the traditional index of the BMI, the anthropometric measures VAI, LAPI, WC, and WHtR had no statistically significant capacity to predict CKD in males. Our results showed that both VAI and LAPI were significantly associated with CKD in the rural population of northeast China. Furthermore, VAI and LAPI were superior to BMI, WC and WHtR for predicting CKD only in females.

The Protective Role of the TOPK/PBK Pathway in Myocardial Ischemia/Reperfusion and H2O2-Induced Injury in H9C2 Cardiomyocytes

T-LAK-cell-originated protein kinase (TOPK) is a PDZ-binding kinase (PBK) that was recently identified as a novel member of the mitogen-activated protein kinase (MAPK) family. It has been shown to play an important role in many cellular functions. However, its role in cardiac function remains unclear. Thus, we have herein explored the biological function of TOPK in myocardial ischemia/reperfusion (I/R) and oxidative stress injury in H9C2 cardiomyocytes. I/R and ischemic preconditioning (IPC) were induced in rats by 3-hour reperfusion after 30-min occlusion of the left anterior descending coronary artery and by 3 cycles of 5-min I/R. Hydrogen peroxide (H2O2) was used to induce oxidative stress in H9C2 cardiomyocytes. TOPK expression was analyzed by western blotting, RT-PCR, immunohistochemical staining, and immunofluorescence imaging studies. The effects of TOPK gene overexpression and its inhibition via its inhibitor HI-TOPK-032 on cell viability and Bcl-2, Bax, ERK1/2, and p-ERK1/2 protein expression were analyzed by MTS assay and western blotting, respectively. The results showed that IPC alleviated myocardial I/R injury and induced TOPK activation. Furthermore, H2O2 induced TOPK phosphorylation in a time-dependent manner. Interestingly, TOPK inhibition aggravated the H2O2-induced oxidative stress injury in myocardiocytes, whereas overexpression relieved it. In addition, the ERK pathway was positively regulated by TOPK signaling. In conclusion, our results indicate that TOPK might mediate a novel survival signal in myocardial I/R, and that its effect on anti-oxidative stress involves the ERK signaling pathway.

Diabetes mellitus is an independent risk factor for atrial fibrillation in a general Chinese population

To explore the association between atrial fibrillation (AF) and diabetes mellitus in a general Chinese population, and the influence of hypertension.

The Association of Ideal Cardiovascular Health and Atherogenic Index of Plasma in Rural Population: A Cross-Sectional Study from Northeast China

In 2010, the American Heart Association has proposed a new concept “ideal cardiovascular health” (CVH) based on seven CVH metrics: smoking, body mass index, physical activity, diet score, total cholesterol, blood pressure, and fasting plasma glucose. We aimed to determine the association of CVH with atherogenic index of plasma (AIP), a strong marker for atherosclerosis (AS). This cross-sectional study was conducted in the rural areas of northeast China and 11,113 middle-aged subjects were enrolled. Seven CVH metrics were classified into ideal, intermediate, and poor groups. AIP was calculated as log (TG/HDL) (triglycerides/high-density lipoprotein cholesterol). AIP > 0.21 was classified into the high AIP group and served as dependent variable. All seven CVH metrics were correlated with AIP. A gradient relationship between the number of poor CVH metrics and the prevalence of high AIP existed. Log binomial regression analysis showed that compared to those with five to seven ideal CVH metrics, individuals with four, three, two, one, and no ideal CVH metrics had 1.67, 2.66, 4.00, 5.30 and 6.50 times higher prevalence for high AIP. The subjects with poor CVH status had 2.73 times higher prevalence for high AIP. We found an inversely gradient relationship between the number of ideal CVH metrics and lower prevalence of high AIP.

Advanced glycation end products promote the proliferation and migration of primary rat vascular smooth muscle cells via the upregulation of BAG3

The present study was aimed to investigate the role of reactive oxygen species (ROS) on advanced glycation end product (AGE)-induced proliferation and migration of vascular smooth muscle cells (VSMCs) and whether Bcl-2-associated athanogene 3 (BAG3) is involved in the process. Primary rat VSMCs were extracted and cultured in vitro. Cell viability was detected by MTT assay and cell proliferation was detected by EdU incorporation assay. Cell migration was detected by wound healing and Transwell assays. BAG3 was detected using qPCR and western blot analysis. Transcriptional and translational inhibitors (actinomycin D and cycloheximide, respectively) were used to study the effect of AGEs on the expression of BAG3 in VSMCs. Lentiviral plasmids containing short hairpin RNA (shRNA) against rat BAG3 or control shRNA were transduced into VSMCs. Cellular ROS were detected by 2′,7′-dichlorofluorescein diacetate (DCFH-DA) staining. Mitochondrial membrane potential was detected by tetramethylrhodamine methyl ester (TMRE) staining. AGEs significantly increased the expression of BAG3 in a dose-and time-dependent manner. Furthermore, AGEs mainly increased the expression of BAG3 mRNA by increasing the RNA synthesis rather than inhibiting the RNA translation. BAG3 knockdown reduced the proliferation and migration of VSMCs induced by AGEs. BAG3 knockdown reduced the generation of ROS and sustained the mitochondrial membrane potential of VSMCs. Reduction of ROS production by N-acetylcysteine (NAC), a potent antioxidant, also reduced the proliferation and migration of VSMCs. On the whole, the present study demonstrated for the first time that AGEs could increase ROS production and promote the proliferation and migration of VSMCs by upregulating BAG3 expression. This study indicated that BAG3 should be considered as a potential target for the prevention and/or treatment of vascular complications of diabetes.

The association of ideal cardiovascular health and left ventricle hypertrophy in rural population of northeast China: A cross-sectional observational study

Abstract In 2010, the American Heart Association (AHA) published a new concept “ideal cardiovascular health” (CVH), which consisted of 4 behaviors (smoking, body mass index [BMI], physical activity, and diet score) and 3 health factors (total cholesterol [TC], blood pressure [BP], and fasting plasma glucose [FPG]). This study was aimed to investigate the association between CVH with left ventricle hypertrophy (LVH) in a rural general population. From January 2012 to August 2013, we conducted this cross-sectional study using a multi-stage cluster sampling method. A representative sample of individuals who were at 35 years or older was selected. All the 7 CVH metrics were estimated for ideal, intermediate, and poor levels. LVH was accessed by echocardiography and classified into concentric remodeling, concentric LVH, and eccentric LVH. The association between CVH and LVH was determined. The final data were obtained from 10,684 adults (5497 men and 5187 women) in the rural areas of northeast China. Overall, the prevalence rates of concentric remodeling, concentric LVH, and eccentric LVH were 5.1%, 4.9%, and 12.8%, respectively. The prevalence of concentric/eccentric LVH was inversely related to the numbers of ideal CVH metrics. Multivariate logistic regression analysis indicated that only poor BP was associated with concentric remodeling among the 7 CVH metrics; poor BP was highly associated with concentric LVH (OR: 8.49; 95% CI: 4.59–15.7); poor BMI was highly associated with eccentric LVH (OR: 5.87; 95% CI: 4.83–7.14). Compared to subjects with 5 to 7 ideal CVH metrics, subjects with 4, 3, 2, 1, and 0 ideal CVH metrics had an increased risk for both concentric and eccentric LVH in a number-dependent manner. The subjects with poor CVH status had a 5.90-fold higher risk of developing concentric LVH and a 3.24-fold higher risk of developing eccentric LVH, compared to subjects with ideal-intermediate CVH. Our study found that an inversely gradient relationship existed between the prevalence of concentric/eccentric LVH with the numbers of ideal CVH metrics. Although not all the 7 CVH metrics were associated with LVH, the components of CVH metrics carried a synergistic effect beyond the risk related to the component alone.

Advanced Glycation End Products Inhibit the Proliferation of Human Umbilical Vein Endothelial Cells by Inhibiting Cathepsin D

We aimed to investigate the effect of advanced glycation end products (AGEs) on the proliferation and migration ability of human umbilical vein endothelial cells (HUVECs). Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay, real-time cell analyzer and 5-Ethynyl-2′-deoxyuridine (EdU) staining. Cell migration was detected by wound-healing and transwell assay. AGEs significantly inhibited the proliferation and migration of HUVECs in a time-and dose-dependent way. Western blotting revealed that AGEs dramatically increased the expression of microtubule-associated protein 1 light chain 3 (LC3) II/I and p62. Immunofluorescence of p62 and acridine orange staining revealed that AGEs significantly increased the expression of p62 and the accumulation of autophagic vacuoles, respectively. Chloroquine (CQ) could further promote the expression of LC3 II/I and p62, increase the accumulation of autophagic vacuoles and promote cell injury induced by AGEs. In addition, AGEs reduced cathepsin D (CTSD) expression in a time-dependent way. Overexpression of wild-type CTSD significantly decreased the ratio of LC 3 II/I as well as p62 accumulation induced by AGEs, but overexpression of catalytically inactive mutant CTSD had no such effects. Only overexpression of wild-type CTSD could restore the proliferation of HUVECs inhibited by AGEs. However, overexpression of both wild-type CTSD and catalytically inactive mutant CTSD could promote the migration of HUVECs inhibited by AGEs. Collectively, our study found that AGEs inhibited the proliferation and migration in HUVECs and promoted autophagic flux, which in turn played a protective role against AGEs-induced cell injury. CTSD, in need of its catalytic activity, may promote proliferation in AGEs-treated HUVECs independent of the autophagy-lysosome pathway. Meanwhile, CTSD could improve the migration of AGEs-treated HUVECs regardless of its enzymatic activity.

The Prevalence of Hypertension Accompanied by High Homocysteine and its Risk Factors in a Rural Population: A Cross-Sectional Study from Northeast China

Previous studies found that hypertension and high homocysteine (HHcy) exhibited a synergistic effect on the risk of cardiovascular diseases. This study aimed to investigate the prevalence of hypertension accompanied by HHcy and its risk factors in the rural areas of northeast China. This study was conducted using a stratified cluster random sampling method, and included 6529 subjects with complete data. Demographic characteristics were obtained from a questionnaire. Blood pressure and anthropometric indices were measured, and serum indices were analyzed. Hypertension accompanied by HHcy was defined as hypertension plus HHcy [homocysteine (Hcy) > 10 µmol/L]. The mean concentration of Hcy was 17.29 μmol/L in the general population. The prevalence of hypertension accompanied by HHcy was so high that it reached 45.1% of our study population and accounted for 86.8% of the total participants with hypertension. Multiple logistic regression analysis indicated that the modifiable risk factors of hypertension accompanied by HHcy included obesity, diabetes, dyslipidemia, and inactive physical activities. We found that the mean level of Hcy, and the prevalences of HHcy and hypertension accompanied by HHcy were very high among the rural population of northeast China. Obesity, diabetes, dyslipidemia, and inactive physical activities were modifiable risk factors of hypertension accompanied by HHcy.