Macrophage ILF3 promotes abdominal aortic aneurysm by inducing inflammatory imbalance in male mice.

Imbalance of proinflammatory and anti-inflammatory responses plays a crucial role in the progression of abdominal aortic aneurysms. ILF3, a known modulator of the innate immune response, is involved in cardiovascular diseases. This study aims to investigate the role of ILF3 in abdominal aortic aneurysm formation. Here, we use multi-omics analyzes, transgenic male mice, and multiplex immunohistochemistry to unravel the underlying involvement of ILF3 in abdominal aortic aneurysms. The results show that macrophage ILF3 deficiency attenuates abdominal aortic aneurysm progression, while elevated macrophage ILF3 exacerbates abdominal aortic aneurysm lesions. Mechanistically, we reveal that macrophagic ILF3 increases NF-κB activity by hastening the decay of p105 mRNA, leading to amplified inflammation in macrophages. Meanwhile, ILF3 represses the anti-inflammatory action by inhibiting the Keap1-Nrf2 signaling pathway through facilitating the ILF3/eIF4A1 complex-mediated enhancement of Keap1 translational efficiency. Moreover, Bardoxolone Methyl treatment alleviates the severity of abdominal aortic aneurysm lesions in the context of elevated ILF3 expression. Together, our findings underscore the significance of macrophage ILF3 in abdominal aortic aneurysm development and suggest its potential as a promising therapeutic target for abdominal aortic aneurysms.

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.

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.

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.