dual-dye-optical-mapping-hearts-from-ryr2r2474s-knock-mice

Dual-Dye Optical Mapping of Hearts from <em>RyR2</em><sup>R2474S</sup> Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia

The pro-arrhythmic cardiac disorder catecholaminergic polymorphic ventricular tachycardia (CPVT) manifests as polymorphic ventricular tachycardia episodes ...

Huazhong University of Science and Technology

The IL-33/ST2 signaling pathway plays an important role in coronary artery disease (CHD); however, few studies have explored how variants in IL-33/ST2 genes influence CHD risk. Here, we examined the association between genetic variants in IL-33, ST2, and IL-1RAcP of the IL-33/ST2 axis and the risk of CHD. We conducted a case-controlled study with 1146 CHD cases and 1146 age- and sex-frequency-matched controls. Twenty-eight single nucleotide polymorphisms (SNPs) in IL-33, ST2, and IL-1RAcP were genotyped by Sequenom MassArray and TaqMan assay. Logistic regression was used to analyze these associations. The SNP rs4624606 in IL-1RAcP was nominally associated with CHD risk. The AA genotype was associated with a 1.85-fold increased risk of CHD (95% confidence interval (CI) = 1.01-3.36; p = 0.045) compared to the TT genotype. Further analysis showed that AA carriers also had a higher risk of CHD than TT + TA carriers (odds ratio (OR) = 1.85; 95% CI = 1.85-3.35; p = 0.043). However, no significant association was observed between variants in IL-33/ST2 genes and CHD risk. Further studies are needed to replicate our results in other ethnic groups with larger sample size.

Associations between variants in IL-33/ST2 signaling pathway genes and coronary heart disease risk.

The aim of this study was to explore whether the circulating frequency and function of myeloid-derived suppressor cells (MDSCs) are altered in patients with acute coronary syndrome (ACS).

Expansion of myeloid-derived suppressor cells in patients with acute coronary syndrome.

This study investigated the relationship between IL-33/ST2 signal pathway gene polymorphisms and myocardial infarction (MI) in Han Chinese. A case-control association analysis was performed on a total of 490 MI patients (MI group) and 929 normal subjects (NC group). Sequenom Mass Array and Taqman genotyping technique were used to analyze the tag single nucleotide polymorphisms (SNPs) in the genes encoding IL-33, ST2, and IL-1RaP (rs11792633, rs1041973 and rs4624606). The results showed that the frequencies of rs4624606 genotypes AA, TT, AT were 0.031, 0.647, 0.322 in MI group and 0.026, 0.712, 0.263 in NC group, and the allele frequencies of A and T were 0.192, 0.808 in MI group and 0.157, 0.843 in NC group. There were significant differences in rs4624606 genotypes and allele frequencies between MI group and NC group (P<0.05). For rs11792633, the allele frequencies of C and T were 0.45, 0.55 in MI group and 0.454, 0.546 in NC group with no significant differences found between the two groups. Compared with genotype CC+TC, rs11792633 genotype TT had an increased risk of hypertension (P<0.05). However, there were no significant differences in the frequencies of rs11792633 genotypes between the two groups. No significant differences were noted in the frequencies of rs1041973 genotype and allele between the two groups. Logistic regression analysis showed that rs4624606 genotypes AT and AA+AT were both significantly associated with MI (AT: OR=1.325, P=0.029, 95% CI=1.03-1.705; AA+AT: OR=1.316, P=0.028, 95% CI=1.03-1.681) after factors such as age, gender, smoking, drinking, body mass index (BMI), triglyceride (TG) and cholesterol were adjusted. Those carrying rs4624606 genotype AT or AA+AT had an increased risk of MI. No associations were found between the polymorphisms of the other two loci with MI. It was concluded that, in the IL33/ST2 signal pathway, the A allele of rs4624606 polymorphism of IL-1RaP gene is a potential independent risk factor for MI, and the genotypes AA+AT and AT are associated with the incidence of MI.

Association of IL33/ST2 signal pathway gene polymorphisms with myocardial infarction in a Chinese Han population.

Impaired glucose regulation (IGR), containing prediabetes and diabetes, is an inflammatory disease. The interleukin-33 (IL-33)/IL-1 receptor-like 1 and IL-1/IL-1 receptor (IL-1R) pathways are involved and play opposite roles. While the IL-1R-associated protein (IL-1Rap) is indispensible for the two pathways, the association between the single-nucleotide polymorphisms (SNPs) of the  gene and IGR has not been determined. TaqMan probe quantitative polymerase chain reaction was used to genotype 11 SNPs in the regions of the  gene selected on the basis of linkage disequilibrium using the HapMap database in a study of 889 individuals (156 IGR patients in the case group and 733 non-diabetic patients in the control group). Logistic regression was applied to control the potential confounders in the multivariate analysis. Among 11 SNPs,  rs3773958 was associated with IGR. Further analysis showed that the odds ratios for GT and GT + GG carriers vs. TT carriers were 1.686 and 1.669, respectively, adjusted for gender, age, weight, waist, drinking, smoking, hypertension, alanine aminotransferase, total cholesterol and triglycerides. For rs3773958 in the non-smoking subgroup, GT and GT + GG carriers had a significantly higher risk of IGR compared to the TT carriers. The same conclusions were drawn using data from non-drinking and non-overweight subgroups. However, interactions between rs3773958 and smoking, drinking or being overweight were not significant. In conclusion, rs3773958 in the  gene region was associated with IGR.

A single-nucleotide polymorphism in the interleukin-1 receptor-associated protein gene is associated with impaired glucose regulation and type 2 diabetes in a case-controlled study.

Recent studies have suggested that interleukin 1 receptor-like 1 (ST2) plays a critical role in pathogenesis of several cardiovascular disease conditions. In this study, we examined association of 13 single nucleotide polymorphisms (SNPs) of ST2 gene with essential hypertension (EH) risk in 1151 patients with EH and 1135 controls. Our study showed that variants rs11685424, rs12999364 and rs3821204 are highly associated with an increase in risk of EH, while rs6543116 is associated with a decrease risk of EH. Notably, in silico analyses suggested the G>C change of rs3821204, which located within the 3'UTR of soluble ST2 mRNA, disrupted a putative binding site for miR202-3p. Functional analyses suggested that miR-202-3p significantly decreased soluble ST2-G mRNA stability and inhibited its endogenous expression. Furthermore, we found increased plasma-soluble ST2 (sST2) level was highly associated with CC genotype of rs3821204 in vivo. Taken together, our findings provide the first evidence that genetic variants in ST2 gene are associated with EH risk and variant rs3821204 may influence the development of EH by controlling sST2 expression.

A functional variant in ST2 gene is associated with risk of hypertension via interfering MiR-202-3p.

ANP32A dysregulation contributes to abnormal megakaryopoiesis in acute megakaryoblastic leukemia.

Deregulation of key regulators of histone modification is important in the initiation and progression of human leukemia. Acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) participates in histone acetylation and its role in acute myeloid leukemia remains unclear. Here we observed significant upregulation of ANP32A in primary AML cells, which was essential for AML cell proliferation, survival, and colony formation. Integrative analysis of the genome-wide histone H3 acetylation and gene expression demonstrated that ANP32A deficiency reduced histone H3 acetylation, in accordance with changes in gene expression. Notably, significant histone H3 acetylation enrichment was associated with mRNA changes in lipid-related genes, including APOC1, PCSK9, P2RX1, and LPPR3. Indeed, over-expression of APOC1 partially compensated the proliferation-defect phenotype in ANP32A deficient AML cells while APOC1 knockdown alone mimicked the effect of ANP32A deficiency. Collectively, our data indicate that ANP32A is a novel regulator of histone H3 acetylation and promotes leukemogenesis.

ANP32A regulates histone H3 acetylation and promotes leukemogenesis.

Myocarditis can be caused by several infectious and noninfectious causes. Treatment for myocarditis is still a difficult task in clinical practice. The gut microbiota is related to cardiovascular diseases such as atherosclerosis and hypertension. However, little is known about the role of the gut microbiota in myocarditis. In our study, we tested the hypothesis that gut dysbiosis is associated with myocarditis. We focused on whether fecal microbiota transplantation (FMT) can be used as an effective treatment for myocarditis. We used an experimental autoimmune myocarditis (EAM) mouse model. Fecal samples were isolated from the control and EAM groups for bacterial genome analysis. We observed an increase in microbial richness and diversity in the myocarditis mice. These changes were accompanied by an increased Firmicutes/Bacteroidetes ratio. We also evaluated the efficacy of FMT for the treatment of myocarditis. EAM mouse guts were repopulated with fecal contents from an untreated male mouse donor. We found that myocardial injury was improved by diminished inflammatory infiltration, showing that IFN-γ gene expression in the heart tissue and CD4IFN-γ cells in the spleen were decreased after FMT in EAM mice. We also found that FMT was able to rebalance the gut microbiota by restoring the Bacteroidetes population and reshaping the microbiota composition. Myocarditis is associated with gut microbiota dysbiosis and characterized by an increased F/B ratio. FMT treatment can rebalance the gut microbiota and attenuate myocarditis. Thus, FMT may be a potential therapeutic strategy for the treatment of myocarditis.

Fecal microbiota transplantation alleviates myocardial damage in myocarditis by restoring the microbiota composition.

Acute liver injury seriously endangers human health. Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, has antioxidative effects in addition to being widely used in the treatment of type 2 diabetes and was reported to ameliorate liver diseases. The aim of this study was to evaluate the hepatoprotective effects of liraglutide on carbon tetrachloride (CCl4)-induced acute liver injury in mice and to investigate the mechanisms involved in this protective effect. Male BALB/c mice were pre-treated with liraglutide (200 μg/kg/day) by hypodermic injection for 3 days before a 0.1% (v/v) CCl4 (10 ml/kg, dissolved in olive oil) intraperitoneal injection, or post-treated with liraglutide once immediately after a CCl4 intraperitoneal injection. The experimental data showed that liraglutide treatment significantly decreased the serum ALT and AST levels and ameliorated the liver histopathological changes induced by CCl4. In addition, liraglutide pre-treatment dramatically increased the number of proliferating cell nuclear antigen (PCNA)-positive hepatocytes and significantly reduced hepatocyte apoptosis after CCl4 treatment. As a consequence, liraglutide pre-treatment significantly prevented CCl4-induced malondialdehyde (MDA) production and increased the activity of the antioxidant superoxide dismutase (SOD) enzyme. In addition, liraglutide pre-treatment significantly ameliorated mitochondrial respiratory functions and ultrastructural features. Furthermore, liraglutide pre-treatment enhances the activation of the NRF2/HO-1 signaling pathway. In summary, liraglutide protects against CCl4-induced acute liver injury by protecting mitochondrial functions and inhibiting oxidative stress, which may partly involve the activation of NRF2/HO-1 signaling pathway.

Protective effect of the glucagon-like peptide-1 analogue liraglutide on carbon tetrachloride-induced acute liver injury in mice.

While there is some evidence and conceptual plausibility that tobacco product use is associated with hypertension incidence and that this association varies by sex, extant longitudinal research had been conducted prior to the emergence of e-cigarette and dual e-cigarette and cigarette use.

Sex Differences in the Association of E-cigarette and Cigarette Use and Dual Use With Self-Reported Hypertension Incidence in US Adults.

Arrhythmia is one of the most common cardiovascular diseases. The search for new drugs to suppress various types of cardiac arrhythmias has always been the focus of attention. In the past decade, the screening of antiarrhythmic active substances from plants has received extensive attention. These natural compounds have obvious antiarrhythmic effects, and chemical modifications based on natural compounds have greatly increased their pharmacological properties. The chemical modification of botanical antiarrhythmic drugs is closely related to the development of new and promising drugs. Therefore, the structural characteristics and action targets of natural compounds with antiarrhythmic effects are reviewed in this paper, so that pharmacologists can select antiarrhythmic lead compounds from natural compounds based on the disease target - chemical structural characteristics.

Article	Year
Associations between variants in IL-33/ST2 signaling pathway genes and coronary heart disease risk. International journal of molecular sciences\| PubMed ID: 25517029	2014
Expansion of myeloid-derived suppressor cells in patients with acute coronary syndrome. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology\| PubMed ID: 25591771	2015
Association of IL33/ST2 signal pathway gene polymorphisms with myocardial infarction in a Chinese Han population. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban\| PubMed ID: 25673187	2015
A single-nucleotide polymorphism in the interleukin-1 receptor-associated protein gene is associated with impaired glucose regulation and type 2 diabetes in a case-controlled study. Biomedical reports\| PubMed ID: 26171164	2015
A functional variant in ST2 gene is associated with risk of hypertension via interfering MiR-202-3p. Journal of cellular and molecular medicine\| PubMed ID: 28121058	2017
ANP32A dysregulation contributes to abnormal megakaryopoiesis in acute megakaryoblastic leukemia. Blood cancer journal\| PubMed ID: 29269781	2017
ANP32A regulates histone H3 acetylation and promotes leukemogenesis. Leukemia\| PubMed ID: 29467488	2018
Fecal microbiota transplantation alleviates myocardial damage in myocarditis by restoring the microbiota composition. Pharmacological research\| PubMed ID: 30508676	2019
Protective effect of the glucagon-like peptide-1 analogue liraglutide on carbon tetrachloride-induced acute liver injury in mice. Biochemical and biophysical research communications\| PubMed ID: 31047638	2019
Sex Differences in the Association of E-cigarette and Cigarette Use and Dual Use With Self-Reported Hypertension Incidence in US Adults. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco\| PubMed ID: 35863748	2023
The characteristics and molecular targets of antiarrhythmic natural products. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie\| PubMed ID: 37897974	2023

Qiang Wen

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