Effect of exercise training on left ventricular remodeling in patients with myocardial infarction and possible mechanisms.

BACKGROUND: A growing amount of evidence provides support for the hypothesis that acute myocardial infarction (AMI) patients should go through cardiopulmonary exercise testing (CPET) about 3-5 d after AMI is diagnosed, make reasonable exercising prescription, and conduct exercise training under guidance. AIM: To investigate the effect of exercise training (ET) on left ventricular systolic function and left ventricular remodeling (LVRM) and to study the possible mechanisms of LVRM by the changes of matrix metallopeptidase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS: Sixty patients with first STEMI undergoing direct percutaneous coronary intervention from February 2008 to October 2008 were randomly assigned to an exercise group (n = 30) and a control group (n = 30). The levels of MMP-9 and TIMP-1 were measured in all patients at 1 d, 10-14 d, 30 d, and 6 mo after admission. Two-dimensional echocardiography and cardiopulmonary exercise testing were done in patients at 10-14 d and 6 mo after admission. RESULTS: There was no significant difference in CPET at baseline between the exercise group and the control group. At 6 mo, the time of exercise, peak and anaerobic threshold values of O2 uptake, and metabolic equivalents increased in both groups, but markedly increased in the exercise group. At baseline, there were no significant differences in left ventricular ejection fraction (LVEF) between the two groups. At 6 mo, LVEF increased in the exercise group, but not in the control group. At 6 mo, the percentage of patients with positive result of LVRM was 26.6% in the exercise group and 52.6% in the control group (P < 0.05). The levels of plasma MMP-9 and TIMP-1 and the ratio of MMP-9 to TIMP-1 in both groups had no significant difference at 1 d and 10-14 d after AMI, but at 30 d and 6 mo, the levels of plasma MMP-9 and TIMP-1 in the exercise group were significantly lower than those in the control group; the ratio of MMP-9 to TIMP-1 in the exercise group was significantly higher than that in the control group. CONCLUSION: ET under supervision based on home condition in early and recovery stage of AMI can improve exercise cardiopulmonary function and prevent the LVRM. Therefore, it may reduce unfavorable remodeling response by decreasing the levels of plasma MMP-9 and TIMP-1 and adjusting the ratio of MMP-9 to TIMP-1 hereafter.

CD8+ T lymphocyte is a main source of interferon-gamma production in Takayasu's arteritis.

Interferon-gamma (IFN-γ) is a cytokine involved in the pathogenesis of Takayasu's arteritis (TAK). However, the source of IFN-γ in TAK patients is not fully clear. We aimed to investigate the source of IFN-γ in TAK. 60 TAK patients and 35 health controls were enrolled. The lymphocyte subsets of peripheral blood were detected by flow cytometry, cytokines were detected by Bio-plex. The correlation among lymphocyte subsets, cytokines and disease activity indexes was analyzed by person correlation. The level of serum IFN-γ in TAK patients was significantly increased (P < 0.05). The percentage of CD3+IFN-γ+ cells in peripheral blood CD3+ cells was significantly higher in TAK patients than that of healthy control group (P = 0.002). A higher proportion of CD3+CD8+IFN-γ+ cells/CD3+IFN-γ+ cells (40.23 ± 11.98% vs 35.12 ± 11.51%, P = 0.049), and a significantly lower CD3+CD4+IFN-γ+/ CD3+CD8+IFN-γ+ ratio (1.34 ± 0.62% vs 1.80 ± 1.33%, P = 0.027) were showed in the TAK group than that of control group. The CD3+CD8+IFN-γ+/CD3+IFN-γ+ ratio was positively correlated with CD3+IFN-γ+cells/ CD3+cells ratio (r = 0.430, P = 0.001), serum IFN-γ level (r = 0.318, P = 0.040) and IL-17 level (r = 0.326, P = 0.031). It was negatively correlated with CD3+CD4+IFN-γ+/CD3+IFN-γ+ ratio (r = - 0.845, P < 0.001). IFN-γ secreted by CD3+CD8 + T cells is an important source of serum IFN-γ in TAK patients.

Risk factors for adverse cardiac events in adults with fulminant myocarditis during hospitalization.

BACKGROUND: Fulminant myocarditis is the critical form of myocarditis that is often associated with heart failure, malignant arrhythmia, and circulatory failure. Patients with fulminant myocarditis who end up with severe multiple organic failure and death are not rare. AIM: To analyze the predictors of in-hospital major adverse cardiovascular events (MACE) in patients diagnosed with fulminant myocarditis. METHODS: We included a cohort of adult patients diagnosed with fulminant myocarditis who were admitted to Beijing Anzhen Hospital from January 2007 to December 2017. The primary endpoint was defined as in-hospital MACE, including death, cardiac arrest, cardiac shock, and ventricular fibrillation. Baseline demographics, clinical history, characteristics of electrocardiograph and ultrasonic cardiogram, laboratory examination, and treatment were recorded. Multivariable logistic regression was used to examine risk factors for in-hospital MACE, and the variables were subsequently assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: The rate of in-hospital MACE was 40%. Multivariable logistic regression analysis revealed that baseline QRS duration > 120 ms was the independent risk factor for in-hospital MACE (odds ratio = 4.57, 95%CI: 1.23-16.94, P = 0.023). The AUC of QRS duration > 120 ms for predicting in-hospital MACE was 0.683 (95%CI: 0.532-0.833, P = 0.03). CONCLUSION: Patients with fulminant myocarditis has a poor outcome. Baseline QRS duration is the independent risk factor for poor outcome in those patients.

Luteolin decreases atherosclerosis in LDL receptor-deficient mice via a mechanism including decreasing AMPK-SIRT1 signaling in macrophages.

Lipid metabolism dysfunction and inflammatory infiltration into arterial walls are associated with the initiation and progression of atherosclerosis. Luteolin has been reported to possess anti-inflammatory actions and protect against tumor necrosis factor-α (TNF-α)-induced vascular inflammation, monocyte adhesion to endothelial cells and the formation of lipid-laden macrophages in vitro. However, the role of luteolin in atherosclerosis and the associated vascular inflammatory remains to be elucidated. The aim of the present study was to investigate the effects of luteolin on plaque development, lipid accumulation and macrophage inflammation low-density lipoprotein receptor-deficient (LDLR-/-) mice with atherosclerosis, as well as the underlying mechanisms in ox-induced THP-1-derived macrophages. Firstly, 9-week-old male C57BL/6 mice were fed a standard chow diet, western diet or western diet supplemented with 100 mg/kg luteolin for 14 weeks. The results of histological staining revealed that 100 mg/kg dietary luteolin ameliorated western diet-induced atherosclerotic plaque development and lipid accumulation in the abdominal aorta. Furthermore, total cholesterol, triglyceride and LDL-cholesterol levels were decreased in the plasma of western diet + luteolin mice compared with those fed with a western diet alone. Quantitative polymerase chain reaction analysis revealed that dietary luteolin inhibited the expression of cluster of differentiation 68, macrophage chemoattractant protein 2 and inflammatory cytokines, including interleukin-6 (IL-6) and TNF-α. Mechanistically, luteolin decreased the total cholesterol level as well as macrophage chemokine and inflammatory cytokine expression in THP-1-derived macrophages via AMP-activated protein kinase (AMPK)-Sirtuin (SIRT)1 signaling following induction with oxidized low-density lipoprotein. The results of the present study suggest that luteolin prevents plaque development and lipid accumulation in the abdominal aorta by decreasing macrophage inflammation during atherosclerosis, which is mediated by mechanisms including AMPK-SIRT1 signaling.

Resveratrol prevents hepatic steatosis and endoplasmic reticulum stress and regulates the expression of genes involved in lipid metabolism, insulin resistance, and inflammation in rats.

Previous research demonstrated that resveratrol possesses promising properties for preventing obesity. Endoplasmic reticulum (ER) stress was proposed to be involved in the pathophysiology of both obesity and hepatic steatosis. In the current study, we hypothesized that resveratrol could protect against high-fat diet (HFD)-induced hepatic steatosis and ER stress and regulate the expression of genes related to hepatic steatosis. Rats were fed either a control diet or a HFD for 12 weeks. After 4 weeks, HFD-fed rats were treated with either resveratrol or vehicle for 8 weeks. Body weight, serum metabolic parameters, hepatic histopathology, and hepatic ER stress markers were evaluated. Moreover, an RT2 Profiler Fatty Liver PCR Array was performed to investigate the mRNA expressions of 84 genes related to hepatic steatosis. Our work showed that resveratrol prevented dyslipidemia and hepatic steatosis induced by HFD. Resveratrol significantly decreased activating transcription factor 4, C/EBP-homologous protein and immunoglobulin binding protein levels, which were elevated by the HFD. Resveratrol also decreased PKR-like ER kinase phosphorylation, although it was not affected by the HFD. Furthermore, resveratrol increased the expression of peroxisome proliferator-activated receptor δ, while decreasing the expression of ATP citrate lyase, suppressor of cytokine signaling-3, and interleukin-1ß. Our data suggest that resveratrol can prevent hepatic ER stress and regulate the expression of peroxisome proliferator-activated receptor δ, ATP citrate lyase, suppressor of cytokine signaling-3, tumor necrosis factor α, and interleukin-1ß in diet-induced obese rats, and these effects likely contribute to resveratrol's protective function against excessive accumulation of fat in the liver.

Resveratrol increases nephrin and podocin expression and alleviates renal damage in rats fed a high-fat diet.

Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD) and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol). Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-κB (NF-κB) and superoxide dismutase (SOD), the content of malondialdehyde (MDA), and the protein levels of tumor necrosis factor (TNF-α), monocyte chemotactic protein-1 (MCP-1), nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-κB activity, increased TNF-α and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-κB signaling pathway that in turn up-regulate nephrin and podocin protein expression.