Hypoxia-associated genes predicting future risk of myocardial infarction: a GEO database-based study

BackgroundPatients with unstable angina (UA) are prone to myocardial infarction (MI) after an attack, yet the altered molecular expression profile therein remains unclear. The current work aims to identify the characteristic hypoxia-related genes associated with UA/MI and to develop a predictive model of hypoxia-related genes for the progression of UA to MI.Methods and resultsGene expression profiles were obtained from the GEO database. Then, differential expression analysis and the WGCNA method were performed to select characteristic genes related to hypoxia. Subsequently, all 10 hypoxia-related genes were screened using the Lasso regression model and a classification model was established. The area under the ROC curve of 1 shows its excellent classification performance and is confirmed on the validation set. In parallel, we construct a nomogram based on these genes, showing the risk of MI in patients with UA. Patients with UA and MI had their immunological status determined using CIBERSORT. These 10 genes were primarily linked to B cells and some inflammatory cells, according to correlation analysis.ConclusionOverall, GWAS identified that the CSTF2F UA/MI risk gene promotes atherosclerosis, which provides the basis for the design of innovative cardiovascular drugs by targeting CSTF2F

Smooth muscle hyperplasia due to loss of smooth muscle α-actin is driven by activation of focal adhesion kinase, altered p53 localization and increased levels of platelet-derived growth factor receptor-β

Mutations in ACTA2, encoding the smooth muscle cell (SMC)-specific isoform of α-actin (α-SMA), cause thoracic aortic aneurysms and dissections and occlusive vascular diseases, including early onset coronary artery disease and stroke. We have shown that occlusive arterial lesions in patients with heterozygous ACTA2 missense mutations show increased numbers of medial or neointimal SMCs. The contribution of SMC hyperplasia to these vascular diseases and the pathways responsible for linking disruption of α-SMA filaments to hyperplasia are unknown. Here, we show that the loss of Acta2 in mice recapitulates the SMC hyperplasia observed in ACTA2 mutant SMCs and determine the cellular pathways responsible for SMC hyperplasia. Acta2−/− mice showed increased neointimal formation following vascular injury in vivo, and SMCs explanted from these mice demonstrated increased proliferation and migration. Loss of α-SMA induced hyperplasia through focal adhesion (FA) rearrangement, FA kinase activation, re-localization of p53 from the nucleus to the cytoplasm and increased expression and ligand-independent activation of platelet-derived growth factor receptor beta (Pdgfr-β). Disruption of α-SMA in wild-type SMCs also induced similar cellular changes. Imatinib mesylate inhibited Pdgfr-β activation and Acta2−/− SMC proliferation in vitro and neointimal formation with vascular injury in vivo. Loss of α-SMA leads to SMC hyperplasia in vivo and in vitro through a mechanism involving FAK, p53 and Pdgfr-β, supporting the hypothesis that SMC hyperplasia contributes to occlusive lesions in patients with ACTA2 missense mutation

Survey of risk factors of coronary heart disease in elderly patients with coronary angiography and establishment of relevant diagnostic model

Objective: To investigate the major risk factors for coronary heart disease (CHD) in elderly patients (≥75 years old) using coronary angiography and develop relevant diagnostic model. Methods: Retrospective analysis was conduc-ted on 548 elderly patients with suspected diagnosis of CHD(≥75 years old) underwent coronary angiography (CAG) treatment in Ruijin Hospital from June 2018 to December 2019. According to CAG results, the patients were divided into two groups :CHD group and control group. The risk factors were analyzed by multivariate Logistic regression, and the predictive value of these factors for the occurrence of CHD in the elderly was evaluated by receiver operator characteristic curve (ROC curve). Results: There were 408 cases in the CHD group and 140 cases in the control group based on results of CAG. The multivariate Logistic regression analysis after baseline analysis showed that elevated level of troponin I(OR=6.828, 95%CI:3.834-12.160, P<0.001), carotid plaque formation(OR=3.440, 95%CI: 1.780-6.650, P<0.001), elevated level of HbA1c(OR=1.532, 95%CI: 1.182-1.987, P=0.001) and white blood cell (WBC) counts (OR=1.187, 95%CI: 1.027-1.371, P=0.021) were risk factors for elderly patients with CHD, While female(OR=0.329, 95%CI: 0.201-0.538, P<0.001), elevated level of direct bilirubin(OR=0.800, 95%CI: 0.679-0.942, P=0.008) and elevated level of hemoglobin(OR=0.976, 95%CI: 0.960-0.992, P=0.003) were protective factors for CHD in elderly patients. The area under the curve of the ROC curve model established with above 7 factors for recognizing CHD in elderly patients was 0.825(P<0.05), with a good diagnostic performance. Conclusions:Unlike the risk factors established among the whole population, such as diabetes, high blood pressure, smoking, hyperlipidemia, obesity and high homocysteine, the increased level of troponin I and carotid artery plaque formation are major risk factors for CHD in the elderly. However, the female gender are potential protective factors for CHD. The corresponding diagnostic model is of certain value for identifying high-risk patients from patients suspected of CHD, and may help reduce excessive and unreasonable use of CAG

Detection and validation of circulating endothelial cells, a blood-based diagnostic marker of acute myocardial infarction.

Circulating endothelial cells (CECs) are markers of vascular damage that have clinical relevance in many diseases, including acute myocardial infarction (AMI), and may be predictors of treatment responses. Herein, we investigated the diagnostic and prognostic value of CEC monitoring in AMI patients and a murine model.CECs were defined as Hoechst 33342(+)/CD45(-/)CD31(+)/CD146(+)/CD133(-) in human blood samples and Hoechst 33342(+)/CD45(-/)CD31(+)/KDR(+)/CD117(-) in murine samples. To evaluate the validity and variability of our CEC detection system, peripheral blood samples of vascular endothelial growth factor-treated athymic nude mice and AMI patients were collected and subjected to intra-assay analysis. CEC detection by flow cytometry and real-time PCR were compared. Blood samples were obtained from 61 AMI patients, 45 healthy volunteers and 19 samples of the original AMI patients accepted one month treatment, via flow cytometry and expressed as a percentage of peripheral blood mononuclear cells.Our CEC detection method was validated and had limited variability. CEC concentrations were higher in AMI patients compared to healthy controls. One month post-treatment, CECs levels decreased significantly.CEC levels may be useful as a diagnostic and prognostic biomarker in AMI patients

Recent Advances in The Polymer Dispersed Liquid Crystal Composite and Its Applications

Polymer dispersed liquid crystals (PDLCs) have kindled a spark of interest because of their unique characteristic of electrically controlled switching. However, some issues including high operating voltage, low contrast ratio and poor mechanical properties are hindering their practical applications. To overcome these drawbacks, some measures were taken such as molecular structure optimization of the monomers and liquid crystals, modification of PDLC and doping of nanoparticles and dyes. This review aims at detailing the recent advances in the process, preparations and applications of PDLCs over the past six years

Down-regulation of S100A4 inhibited cell proliferation of A7r5 and MMP2/MMP9 expression <i>in vitro</i>.

<p>A, The results of cell proliferation ability of A7r5 cells after transfection with S100A4 siRNA at different time intervals (0, 24, 48, 72 h). *Represents <i>P</i><0.05, compared to the control nonspecific siRNA-transfected group and the untreated A7r5 group at 24, 48, and 72 h. B, RT-PCR analysis of MMP2 mRNA isolated from A7r5 cells from 3 groups after transfection at different time intervals (0, 24, 48, 72 h). * and # represents <i>P</i><0.05, compared to the control nonspecific siRNA-transfected group and the untreated A7r5 group at 24, 48, and 72 h. C, RT-PCR analysis of MMP9 mRNA isolated from A7r5 cells from 3 groups after transfection at different time intervals (0, 24, 48, 72 h). * and # represents <i>P</i><0.05, compared to the control nonspecific siRNA-transfected group and the untreated A7r5 group at 24, 48, and 72 h. D, Western blot analysis of the knockdown efficiency of S100A4 by siRNA. E, Western blot analysis of MMP2/MMP9 protein isolated from A7r5 cells from 3 groups after transfection at different time intervals (0, 24, 48, 72 h).</p

Disruption of the elastic lamellar structure at all time-points after thoracic aortic aneurysm induction.

<p>A, Representative Weigert staining and hematoxylin/eosin staining of sections of the aorta from NaCl-treated and TAA-induced rats. Scale bar = 100 µm. B, Grading of elastin degradation at each time-point in the two groups. C, Quantitation of intima-media thickness (IMT) in the two groups. Bars represent the SEM, *<i>P</i><0.05 compared with the control group (n = 6 for each group).</p

Increased transcription levels of MMP-2, MMP-9 and S100A4A at all time-points after thoracic aortic aneurysm induction.

<p>A, Real-time PCR examination of MMP-2, MMP-9 and S100A4 at each time-point in the two groups, and mRNA levels are normalized to the mRNA of <i>β</i>-actin. Bars represent the SEM, *<i>P</i><0.05 compared with control group (n = 6 for each group). B, Positive correlations between the mRNA levels of S100A4 and MMPs over time post-TAA induction.</p