陈岩
阜外华中心血管病医院 心血管内科
Background:Genome-wide association studies for various hemorheological characteristics have not been reported. We aimed to identify genetic loci associated with hemorheological indexes in a cohort of healthy Chinese Han individuals.Methods:Genotyping was performed using Applied Biosystems Axiom™ Precision Medicine Diversity Array in 838 individuals, and 6,423,076 single nucleotide polymorphisms were available for genotyping. The relations were examined in an additive genetic model using mixed linear regression and combined with identical by descent matrix.Results:We identified 38 genetic loci (p < 5 × 10-6) related to hemorheological traits. In which, LOC102724502-OLIG2 rs28371438 was related to the levels of nd30 (p = 8.58 × 10-07), nd300 (p = 1.89 × 10-06), erythrocyte rigidity (p = 1.29 × 10-06), assigned viscosity (p = 6.20 × 10-08) and whole blood high cut relative (p = 7.30 × 10-08). The association of STK32B rs4689231 for nd30 (p = 3.85 × 10-06) and nd300 (p = 2.94 × 10-06) and GTSCR1-LINC01541 rs11661911 for erythrocyte rigidity (p = 9.93 × 10-09) and whole blood high cut relative (p = 2.09 × 10-07) was found. USP25-MIR99AHG rs1297329 was associated with erythrocyte rigidity (p = 1.81 × 10-06) and erythrocyte deformation (p = 1.14 × 10-06). Moreover, the association of TMEM232-SLC25A46 rs3985087 and LINC00470-METTL4 rs9966987 for fibrinogen (p = 1.31 × 10-06 and p = 4.29 × 10-07) and plasma viscosity (p = 1.01 × 10-06 and p = 4.59 × 10-07) was found.Conclusion:These findings may represent biological candidates for hemorheological indexes and contribute to hemorheological study.
Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie 2022
The prevention and treatment of coronary heart disease (CHD) is a difficult problem to be solved urgently. Genetic factors play a crucial role in CHD development. This study aimed to investigate the association of GAS5/METTL14/ESR1 polymorphisms with CHD susceptibility. We carried out a case-control study that included 506 patients and 506 healthy subjects to detect the correlation between GAS5/METTL14/ESR1 polymorphisms and CHD risk in a Chinese population. Odds ratios (OR) and 95% confidence intervals (CI) were computed to assess the associations. Our study showed that GAS5 rs17359906 (OR 2.32, p = 0.020) and rs75315904 (OR 0.41, p = 0.039) were related to the risk of CHD in females. ESR1 rs6927072 (OR 1.76, p = 0.007) and rs4870061 (OR 0.74, p = 0.036) correlated with CHD risk in age ≤ 60 years. GAS5 rs17359906 (OR 0.10, p = 0.032) and ESR1 rs3020308 (OR 2.73, p = 0.041) were associated with an increased susceptibility to CHD in smokers. We also found that METTL14 rs4834698 (OR 1.57, p = 0.044) and ESR1 rs4870061 (OR 0.62, p = 0.040) were associated with CHD susceptibility in non-drinkers. Besides, METTL14 rs17050450 (OR 0.48, p = 0.029) and ESR1 rs3853248 (OR 1.61, p = 0.018) had the susceptibility of CHD patients with diabetes. Our study indicated that GAS5/METTL14/ESR1 polymorphisms were associated with CHD risk, which might provide a new understanding of CHD in a Chinese population.
Functional & integrative genomics 2022
Vulnerable plaques are plaques which are susceptible to rupture or thrombosis and trigger a series of adverse events such as coronary disorders. CCL2 is a soluble basic protein belonging to the CC subfamily. Previous studies have been investigated on the correlation between inflammatory factors and clinical events, but there are few studies on the correlation between CCL2 and plaque characteristics. Our study found that the high expression of CCL2 is involved in multiple processes in the genesis and progression of coronary artery disease, and would be a potential clinical prognostic indicator. In addition, high expression of CCL2 may be related to gene pathways such as Nod-like receptor signaling pathway, suggesting that CCL2 is involved in the inflammatory response and immune process of coronary artery disease.
Experimental biology and medicine (Maywood, N.J.) 2020
Berberine (BBR) is routinely prescribed in many Asian countries to treat diarrhea. Evidence from both animal and clinical investigations suggests that BBR exerts diverse pharmacological activities, including antidiabetic, antineoplastic, antihypertensive, and antiatherosclerotic effects. This study aimed to explore the cardioprotective mechanisms of BBR and to elucidate the modulations between autophagy and mitochondrial function during hypoxia/reoxygenation (H/R) in H9c2 cells. The degree of autophagic flux was assessed by pretreating H9c2 cells with BBR prior to H/R exposure and measuring the expression levels of Beclin-1 and green fluorescent protein (GFP)-labeled LC3B fusion proteins as well as the LC3II/LC3I ratio. The mitochondrial membrane potential (△Ψm) in H9c2 cells was evaluated by detecting rhodamine-123 fluorescence using flow cytometry. The results revealed that pretreatment with BBR upregulated autophagic flux and protected against the loss of the △Ψm in H9c2 cells subjected to H/R. We conclude that BBR attenuates mitochondrial dysfunction by inducing autophagic flux.
Cell stress & chaperones 2020
Cardiomyocyte apoptosis induced by hypoxia and ischemia plays important roles in heart dysfunction after acute myocardial infarction (AMI). However, the mechanism of apoptosis induction remains unclear. A previous study reported that Y-box protein 1 (YB1) is upregulated after myocardial hypoxia/reoxygenation or ischemia/reperfusion (H/R or I/R, respectively) injury; however, whether YB1 is associated with H/R-induced cardiomyocyte apoptosis is completely unknown. In the present study, we investigated the roles of YB1 in H/R-induced cardiomyocyte apoptosis and the possible underlying molecular mechanisms. In vitro, H/R treatment upregulated the YB1 expression in H9C2 cells, whereas YB1 knockdown inhibited H/R-induced cardiomyocyte apoptosis and induced H9C2 cell proliferation via Src homology region 2 domain-containing phosphatase 1 (SHP-1)-mediated activation of signal transducer and activator of transcription 3 (STAT3). In vivo, YB1 knockdown ameliorated AMI, reducing infarct size, cardiomyocyte apoptosis, and oxidative stress, via SHP-1-mediated inactivation of STAT3. Additionally, YB1 knockdown inhibited H/R- or I/R-induced oxidative stress in vitro and in vivo. H/R and I/R increase YB1 expression, and YB1 knockdown ameliorates AMI injury via SHP-1-dependent STAT3 inactivation.
Journal of cellular physiology 2020
Acute myocardial infarction (AMI), as a severe consequence of coronary atherosclerotic heart disease, always contributes to the loss of myocardial cells. Mounting evidence shows that annexin protects the myocardium from ischemic injury. In this study, we examine the inhibition of annexin A3 (ANXA3) on AMI through the phosphatidylinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. We selected rats to build an AMI model which was then assigned into different groups. The hemodynamic parameters after transfection were detected by using enzyme-linked immunosorbent assay. The effect of silencing of ANXA3 on inflammatory reaction and the PI3K/Akt signaling pathway was assessed. Rats transfected with ANXA3-short hairpin RNA had alleviated hemodynamics, inflammatory reaction, decreased infarct size, α-smooth muscle actin, Collagen I, and Collagen III as well as an increased vascular endothelial growth factor. Silencing ANAX3 would promote repair and healing of myocardial tissue by activation of the PI3K/Akt signaling pathway. Collectively, our study provides evidence that the downregulation of ANXA3 promotes the repair and healing of myocardial tissues by activating the PI3K/Akt signaling pathway.
Journal of cellular physiology 2019
To investigate the effect of miR-181a targeting XIAP gene on the apoptosis of cardiomyocytes induced by hypoxia/reoxygenation (H/R) and its mechanism. The primary cultured cardiomyocytes were treated with hypoxia for 3 hours and reoxygenation for 4 hours to construct H/R cell model. The expression of miR-181a and XIAP messenger RNA in cardiomyocytes was detected by reverse-transcription polymerase chain reaction, and the expression of XIAP protein in cardiomyocytes was detected by Western blot analysis. H/R cardiomyocytes with low expression of miR-181a and overexpression of XIAP were constructed, and the effects of low expression of miR-181a and upregulation of XIAP on cardiomyocyte apoptosis were detected by flow cytometry. A dual luciferase reporter assay was used to detect the target relationship between miR-181a and XIAP. Further, H/R myocardial cells with low XIAP expression were constructed to observe the effect of downregulation of XIAP expression on apoptosis of myocardial cells with low expression of microarray-181a. The expression of apoptosis-related proteins Bax and Bcl-2 in myocardial cells was detected by Western blot analysis. After H/R treatment, the expression of microRNAs-181a was high but that of XIAP was low. The apoptosis of cardiomyocytes could be inhibited by both the low expression of miR-181a and the upregulation of XIAP. The results of dual luciferase reporter gene showed that XIAP was a potential target gene for miR-181a. The inhibitory effect of low expression of miR-181a on myocardial apoptosis could be reversed and the inhibitory effect of low expression of miR-181a on Bax protein expression and the promotion of Bcl-2 protein expression could be reversed by the downregulation of XIAP. MiR-181a can inhibit the apoptosis of hypoxic-reoxygenated cardiomyocytes by targeting XIAP to downregulate Bax and upregulate Bcl expression.
Journal of cellular biochemistry 2019
AIMS:Y-box protein 1 (YB1) is a key regulator of inflammatory mediators. However, the roles of YB1 in oxidized low-density lipoprotein (ox-LDL)-induced macrophage inflammation and lipid uptake remain less understood. Thus, we explored the roles of YB1 in ox-LDL-induced macrophage inflammation and lipid uptake and its underlying molecular mechanisms.METHODS:An ox-LDL-induced atherosclerosis (AS) model was used in this study. Western blotting, RT-PCR, immunofluorescence, ELISA, dil-ox-LDL staining, a dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) and in vivo experiments were used to detect each target.RESULTS:ox-LDL downregulates YB1 expression in THP-1-derived macrophages and human monocyte-derived macrophages (hMDMs) via the NF-κB pathway. Downregulation of YB1 is facilitated by lipid uptake in macrophages, and CD36 is involved in this process. Furthermore, YB1 suppresses CD36 protein levels by directly binding to the coding sequence of the CD36 gene to promote CD36 mRNA decay but does not affect its mRNA transcription. Additionally, YB1 knockdown enhances the inflammatory response and lipid deposition via the NF-κB pathway in vivo.CONCLUSION:ox-LDL decreases YB1 expression in macrophages, resulting in enhanced inflammatory responses by affecting NF-κB and facilitating lipid uptake by promoting scavenger receptor CD36 mRNA decay.
Free radical biology & medicine 2019