Smooth muscle NF90 deficiency ameliorates diabetic atherosclerotic calcification in male mice via FBXW7-AGER1-AGEs axis.

Hyperglycemia accelerates calcification of atherosclerotic plaques in diabetic patients, and the accumulation of advanced glycation end products (AGEs) is closely related to the atherosclerotic calcification. Here, we show that hyperglycemia-mediated AGEs markedly increase vascular smooth muscle cells (VSMCs) NF90/110 activation in male diabetic patients with atherosclerotic calcified samples. VSMC-specific NF90/110 knockout in male mice decreases obviously AGEs-induced atherosclerotic calcification, along with the inhibitions of VSMC phenotypic changes to osteoblast-like cells, apoptosis, and matrix vesicle release. Mechanistically, AGEs increase the activity of NF90, which then enhances ubiquitination and degradation of AGE receptor 1 (AGER1) by stabilizing the mRNA of E3 ubiquitin ligase FBXW7, thus causing the accumulation of more AGEs and atherosclerotic calcification. Collectively, our study demonstrates the effects of VSMC NF90 in mediating the metabolic imbalance of AGEs to accelerate diabetic atherosclerotic calcification. Therefore, inhibition of VSMC NF90 may be a potential therapeutic target for diabetic atherosclerotic calcification.

Deficiency of smooth muscle cell ILF3 alleviates intimal hyperplasia via HMGB1 mRNA degradation-mediated regulation of the STAT3/DUSP16 axis.

Intimal hyperplasia is a complicated pathophysiological phenomenon attributable to in-stent restenosis, and the underlying mechanism remains unclear. Interleukin enhancer-binding factor 3 (ILF3), a double-stranded RNA-binding protein involved in regulating mRNA stability, has been recently demonstrated to assume a crucial role in cardiovascular disease; nevertheless, its impact on intimal hyperplasia remains unknown. In current study, we used samples of human restenotic arteries and rodent models of intimal hyperplasia, we found that vascular smooth muscle cell (VSMC) ILF3 expression was markedly elevated in human restenotic arteries and murine ligated carotid arteries. SMC-specific ILF3 knockout mice significantly suppressed injury induced neointimal formation. In vitro, platelet-derived growth factor type BB (PDGF-BB) treatment elevated the level of VSMC ILF3 in a dose- and time-dependent manner. ILF3 silencing markedly inhibited PDGF-BB-induced phenotype switching, proliferation, and migration in VSMCs. Transcriptome sequencing and RNA immunoprecipitation sequencing depicted that ILF3 maintained its stability upon binding to the mRNA of the high-mobility group box 1 protein (HMGB1), thereby exerting an inhibitory effect on the transcription of dual specificity phosphatase 16 (DUSP16) through enhanced phosphorylation of signal transducer and activator of transcription 3 (STAT3). Therefore, the results both in vitro and in vivo indicated that the loss of ILF3 in VSMC ameliorated neointimal hyperplasia by regulating the STAT3/DUSP16 axis through the degradation of HMGB1 mRNA. Our findings revealed that vascular injury activates VSMC ILF3, which in turn promotes intima formation. Consequently, targeting specific VSMC ILF3 may present a potential therapeutic strategy for ameliorating cardiovascular restenosis.

ILF3 is responsible for hyperlipidemia-induced arteriosclerotic calcification by mediating BMP2 and STAT1 transcription.

Calcification is common in atherosclerotic plaque and can induce vulnerability, which further leads to myocardial infarction, plaque rupture and stroke. The mechanisms of atherosclerotic calcification are poorly characterized. Interleukin enhancer binding factor 3 (ILF3) has been identified as a novel factor affecting dyslipidemia and stroke subtypes. However, the precise role of ILF3 in atherosclerotic calcification remains unclear. In this study, we used smooth muscle-conditional ILF3 knockout (ILF3SM-KO) and transgenic mice (ILF3SM-Tg) and macrophage-conditional ILF3 knockout (ILF3M-KO) and transgenic (ILF3M-Tg) mice respectively. Here we showed that ILF3 expression is increased in calcified human aortic vascular smooth muscle cells (HAVSMCs) and calcified atherosclerotic plaque in humans and mice. We then found that hyperlipidemia increases ILF3 expression and exacerbates calcification of VSMCs and macrophages by regulating bone morphogenetic protein 2 (BMP2) and signal transducer and activator of transcription 1 (STAT1) transcription. We further explored the molecular mechanisms of ILF3 in atherosclerotic calcification and revealed that ILF3 acts on the promoter regions of BMP2 and STAT1 and mediates BMP2 upregulation and STAT1 downregulation, which promotes atherosclerotic calcification. Our results demonstrate the effect of ILF3 in atherosclerotic calcification. Inhibition of ILF3 may be a useful therapy for preventing and even reversing atherosclerotic calcification.

A risk factor-based predictive model for new-onset hypertension during pregnancy in Chinese Han women.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is one of the leading causes of maternal and neonatal mortality, increasing the long-term incidence of cardiovascular diseases. Preeclampsia and gestational hypertension are the major components of HDP. The aim of our study is to establish a prediction model for pregnant women with new-onset hypertension during pregnancy (increased blood pressure after gestational age > 20 weeks), thus to guide the clinical prediction and treatment of de novo hypertension. METHODS: A total of 117 pregnant women with de novo hypertension who were admitted to our hospital's obstetrics department were selected as the case group and 199 healthy pregnant women were selected as the control group from January 2017 to June 2018. Maternal clinical parameters such as age, family history and the biomarkers such as homocysteine, cystatin C, uric acid, total bile acid and glomerular filtration rate were collected at a mean gestational age in 16 to 20 weeks. The prediction model was established by logistic regression. RESULTS: Eleven indicators have statistically significant difference between two groups (P < 0.05). These 11 factors were substituted into the logistic regression equation and 7 independent predictors were obtained. The equation expressed including 7 factors. The calculated area under the curve was 0.884(95% confidence interval: 0.848-0.921), the sensitivity and specificity were 88.0 and 75.0%. A scoring system was established to classify pregnant women with scores ≤15.5 as low-risk pregnancy group and those with scores > 15.5 as high-risk pregnancy group. CONCLUSIONS: Our regression equation provides a feasible and reliable means of predicting de novo hypertension after pregnancy. Risk stratification of new-onset hypertension was performed to early treatment interventions in high-risk populations.

Myocarditis presenting as typical acute myocardial infarction: A case report and review of the literature.

BACKGROUND: Myocarditis refers to a variety of myocardial inflammatory lesions. A variety of factors such as infection and physical and chemical factors can cause myocarditis. Depending on the severity of myocardial damage, myocarditis patients can manifest heart failure, cardiogenic shock, and even sudden death. Here we present a case of viral myocarditis that mimicked acute coronary syndrome. CASE SUMMARY: A middle-aged male patient presented with chest pain and elevated troponin I after a flu-like infection. This patient had a history of hypertension and a habit of alcohol and tobacco use. Electrocardiography showed typical changes in acute myocardial infarction, with the T-wave increasing. Coronary angiogram revealed no stenosis. Cardiac magnetic resonance imaging revealed edema of the middle and apical septal and apical anterior walls on T2-weighted images and the T1 mapping. Late gadolinium enhancement of the middle and apical septal and apical anterior walls could be found. Rubella virus immunoglobulin G and immunoglobulin M antibodies were abnormally elevated. The patient was given antiviral and antibiotic treatments, and serum biomarkers and electrocardiograph returned to normal after 5 d of treatment. After one-year follow-up, the patient showed no symptoms, and cardiac magnetic resonance showed that myocardial thickness was significantly thinner than before, and fibrosis was less than before. CONCLUSION: This case illustrates the utility of cardiac magnetic resonance for diagnosis of infarction-like myocarditis when the angiogram is normal.

Impact of serum 25-hydroxyvitamin D on cardiac prognosis in Chinese patients with heart failure.

There is growing evidence that suggests the association of vitamin D status with the development and progression of heart failure (HF). The objective of the present study is to assess the impact of concentration of serum 25-hydroxyvitamin D (25(OH)D) on cardiac prognosis in patients with HF. Between 1 January 2015 and 31 December 2016, we consecutively recruited patients with HF. Patients were followed prospectively for a median duration of 1 year. Serum concentration of 25(OH)D was measured with competitive chemiluminescent immunoassay. The endpoints were cardiac events, including CVD death and rehospitalisation for worsening HF. Univariate and multivariable adjustments were performed with Cox proportional-hazard regression analyses. The 25(OH)D concentration was obtained in 343 patients with a median value of 17·4 (interquartile range 12·6-23·4) ng/ml. There were 102 cardiac events, including forty-three deaths and fifty-nine rehospitalisations. Multivariate Cox hazard analysis found that the serum concentration 25(OH)D was independently associated with cardiac events (hazard ratio 0·93, 95 % CI 0·88, 0·97) and CVD mortality (hazard ratio 0·83; 95 % CI 0·77, 0·89) after adjustment for confounding factors. We divided the HF patients into four groups according to the 25(OH)D quartiles. Kaplan-Meier analysis found that the patients with lower serum 25(OH)D concentration had a higher risk of cardiac events or CVD mortality than those with high serum 25(OH)D concentration (log-rank test P < 0·001 and P = 0·032). Decreased serum concentrations of 25(OH)D were associated with cardiac prognosis and CVD mortality in a Chinese population with HF independent of other baseline HF markers.

A risk prediction model for renal damage in a hypertensive Chinese Han population.

Backgroud: While numerous risk factors for renal damage in the hypertensive population have been reported, there is no single prediction model. The purpose of this study was to develop a model to comprehensively evaluate renal damage risk among hypertensive patients. Methods: We analyzed the data of 582 Chinese hypertensive patients from 1 January 2013 to 30 June 2016. Basic patient information was collected along with laboratory test results. According to the albumin-to-creatinine ratio, the subjects were divided into a hypertension with renal damage group and a hypertension without renal damage group. The prediction model was established by logistic regression based on principal component analysis, and the area under the receiver operating characteristic curve was used to evaluate the predictive performance of the model.Results: There are 11 indicators have statistically significant difference between the two groups (P < 0.05); The equation expressed including all 11 risk factors was as follows: Y = (-0.236) - 0.1705 (sex) - 0.0098 (age) - 0.1067 (smoking history) + 0.0303 (drinking history) - 0.3031 (CHD) + 0.1276 (diabetes history) - 0.0596 (CRP level) - 0.0732 (CysC level) + 0.0949 (ß2-MG level) + 0.5407 (blood pressure type) + 0.6470 (RRI). The calculated AUC was 74.4%; The risk in males was much higher than that in females of the same age. However, with increasing age, the male:female risk ratio gradually decreased. Conclusion: Eleven  indicators (including sex, age, smoking history, drinking history, coronary heart disease, diabetes history, C-reactive protein, CystatinC,  ß2-microglobulin protein, blood pressure type, renal artery resistance index)  may be the risk factors of renal damage in hypertension. Our regression equation provides a feasible means of predicting renal damage in Chinese hypertensive populations, and the model showed good predictive power. In addition, estrogen may confer a protective effect on the kidney. Abbreviations: PCA: principal component analysis; SLPs: synthetic latent predictors; CKD: chronic kidney disease; RRI: renal artery resistance index; MLR: multivariate logistic regression; CHD: coronary heart disease; UACR: urine trace albumin/uric creatinine ratio; CysC: CystatinC; TG: Triglyceride; CHO: cholesterol; HDL: high-density lipoprotein cholesterol; LDL: low-density lipoprotein cholesterol; CRP: C-reactive protein; HCY: homocysteine; UA: uric acid; AUC: area under the ROC curve; CVE: cardiovascular events; RFF: renal function related factor; PHF: personal history related factor; CVF: cardiovascular factor; GMF: glucose metabolism factor; IF: inflammatory factor; BPF: blood pressure factor.

Lycium barbarum polysaccharide exhibits cardioprotection in an experimental model of ischemia-reperfusion damage.

Cardiovascular diseases are a major cause of mortality and disability worldwide. The present study investigated the cardio-protective effects of polysaccharides extracted from Lycium barbarum (LB), the fruit of which is traditionally used in Chinese medicine. Polysaccharides were characterized using Fourier transform infrared spectroscopy and high­performance liquid chromatography techniques. The present study demonstrated that LB polysaccharides are composed of glucose and fructose monosaccharides in a molar ratio of 1:2. A total of 36 rats were divided into three groups plus a control group, with nine animals in each group, and were used for studying the cardioprotective effects of LB polysaccharides. The low­dose group received 150 mg/kg body weight (BW) polysaccharides and the high­dose group received 300 mg/kg BW polysaccharides. The results demonstrated that the LB polysaccharides reduced the levels of myocardial lactate dehydrogenase and increased the sodium­potassium ATPase and calcium ATPase activities in rats with heart ischemia­reperfusion injury. In addition, there was a decrease in the myocardial Bax­positive expression and the rate of myocardial cell apoptosis, along with a dose­dependent increase in Bcl­2­positive expression. Therefore, it was concluded that LB polysaccharides are able to halt the progression of cardiovascular diseases.

A Non-Targeted Liquid Chromatographic-Mass Spectrometric Metabolomics Approach for Association with Coronary Artery Disease: An Identification of Biomarkers for Depiction of Underlying Biological Mechanisms.

BACKGROUND We performed non-targeted metabolomics analysis using liquid chromatography-mass spectrometry coupled technique to explore the biological mechanism of coronary artery disease (CAD) events for improved prediction. MATERIAL AND METHODS We studied the association of CAD events in 4092 individuals and observed the replication of sphingomyelin (28:1), lysophosphatidylcholine (18:2), lysophosphatidylcholine (18:1), and monoglyceride (18:2), which were independent of main CAD risk factors. RESULTS We found that these 4 metabolites were responsible for traditional risk factors and also contributed to the modifications related to reclassification and discrimination. Monoglycerides (MonoGs) were positively associated with C-reactive proteins and body mass index, while lysophosphatidylcholines (LPPCs), which had less evidence of subclinical CAD in an additional 1010 participants, yielded a reverse pattern. An association between monoGs and CAD independence of triglycerides (triGs) were also observed. On the basis of Mendelian randomization analysis, we observed a positive but weak irregular effect (odds ratio per unit increase in standard deviation in monoG=1.11, P-value=0.05) on CAD. CONCLUSIONS Our work establishes the relationship of metabolome with coronary artery disease and explains the biological mechanism of CAD events, as we identified the above-mentioned metabolites along with the evidence supporting their clinical use.

[Effect of Shexiang Baoxin pill on coronary vasodilation by analysis of coronary angiography].

OBJECTIVE: To evaluate the effect of Shexiang Baoxin Pill (SBP) on coronary vasodilation by analysis of coronary angiography (CAG). METHODS: A consecutive cohort of 300 patients who underwent CAG between January 2013 and July 2013 were recruited and randomly assigned to 2 groups before operation. Patients in the SBP group sublingually took SBP, while those in the control group sublingually took placebos. All patients repeatedly underwent CAG 5 min after administration. The vascular diameter was calculated by quantitative angiography analysis method. The diameter of the left anterior descending coronary artery was measured in patients whose coronary arteries had no stenosis. The narrowest vascular diameter was measured in patients whose coronary arteries had stenosis. The heart rate, blood pressure, and the vascular diameter were compared between before and after administration in the two groups. RESULTS: In the two groups, there was no significant difference in changes of heart rate, systolic pressure, or diastolic pressure between before and after administration (all P > 0.05). There were 64 patients with normal CAG in the two groups, 30 in the control group and 34 in the SBP group. CAG showed there were 236 patients with stenotic coronary artery, 110 in the control group and 126 in the SBP group. The vascular diameter was obviously larger in patients in the SBP group with normal or abnormal CAG after administration (all P < 0.01). It was also obviously larger than that of the control group after administration (P < 0.05, P < 0.01). CONCLUSION: SBP could dilate both normal coronary artery and lesioned coronary arteries, but did not lead to fastened heart rate and decreased blood pressure.

[Long-term outcome of percutaneous balloon mitral valvuloplasty in patients with rheumatic mitral valve stenosis].

OBJECTIVE: To observe the outcome of percutaneous balloon mitral valvuloplasty (PBMV) in patients with rheumatic mitral valve stenosis. METHODS: From April 1992 to November 2008, 1768 patients underwent PBMV in our hospital.Clinical and echocardiographic follow up data were analyzed in 426 patients from April 1992 to August 1998. Left atrial pressure and the mitral valve gradient (MVG) were measured before and immediately after PBMV in all patients. RESULTS: PBMV was successful in 1748 out of 1768 patients (98.86%). Left atrial pressure decreased from (38 +/- 7) mm Hg (1 mm Hg = 0.133 kPa) to (12 +/- 4) mm Hg (P < 0.001), MVG decreased from (28 +/- 6) mm Hg to (8 +/- 3) mm Hg (P < 0.001) and the area of the mitral valve increased from (0.98 +/- 0.26) cm(2) to (1.97 +/- 0.39) cm(2) (P < 0.001) post PBMV. The main complications included death (n = 2), acute pericardial effusion (n = 1), severe mitral regurgitation (n = 12), cerebral embolism (n = 2) and pulmonary edema (n = 1). Ten years follow up was finished in 426 patients and 288 patients (67.6%) were still in NYHA class Ior II without mitral valve replace operation or repeated PBMV, restenosis was evidenced in 140 patients (33.3%) and 31 patients dead (7.5%). CONCLUSION: PBMV was an effective therapy option for patients with rheumatic mitral valve stenosis.

The variations of mercury in sediment profiles from a historically mercury-contaminated reservoir, Guizhou province, China.

Baihua Reservoir in Guizhou Province, China, experienced serious Hg contamination from Guizhou Organic Chemical Plant (GOCP) between 1971 and 1997. However, the biogeochemical cycling of Hg in this reservoir is not well studied. Sediment cores were collected in fall 2002, spring 2003 and in spring and fall 2004. THg and MeHg concentrations in all sediment profiles ranged from 0.26 to 38.9 mg/kg and from 0.5 to 27.5 microg/kg (d.w.), respectively. The distribution of THg in sediment cores was characterized by a few peaks, which may correspond to the Hg-containing wastewater discharge history of the GOCP. The average THg concentrations in sediments cores decreased from upstream to downstream due to the deposition of particulate Hg, which is the major form of Hg in water. THg and MeHg concentrations in pore water varied from 6.1 to 5860 ng/L and from 0.3 to 15.4 ng/L, respectively, which were significantly higher than levels in the overlying water column. Average diffusive flux from sediment to water is 1642 and 36 ng/m2/day for THg and MeHg. The spatial distribution of THg in pore water from upstream to downstream showed the same trend as the sediment, but MeHg in pore water did not show a declining pattern with distance from the GOCP. These results suggested that sediments experienced serious contamination of Hg, and the contaminated sediment is an important Hg contamination source to the overlying water.