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OBJECTIVE: To explore the genetic basis for a patient with Dilated cardiomyopathy. METHODS: A patient admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University in April 2022 was selected as the study subject. Clinical data and family history of the patient was collected. Targeted exome sequencing was carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of the American College of Medical Genetics and Genomics (ACMG). RESULTS: DNA sequencing revealed that the patient has harbored a heterozygous c.5044dupG frameshift variant of the FLNC gene. Based on the ACMG guidelines, the variant was predicted to be likely pathogenic (PVS1+PM2_Supporting+PP4). CONCLUSION: The heterozygous c.5044dupG variant of the FLNC gene probably underlay the pathogenesis in this patient, which has provided a basis for the genetic counseling for his family.
Subject(s)
Cardiomyopathy, Dilated , Humans , Cardiomyopathy, Dilated/genetics , Genetic Testing , Genetic Counseling , Computational Biology , Frameshift Mutation , Mutation , FilaminsABSTRACT
Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. However, a detailed DNA methylation (DNAme) landscape has not yet been elucidated. Our study combined DNAme and transcriptome profiles for HCM myocardium and identify aberrant DNAme associated with altered myocardial function in HCM. The transcription of methylation-related genes did not significantly differ between HCM and normal myocardium. Nevertheless, the former had an altered DNAme profile compared with the latter. The hypermethylated and hypomethylated sites in HCM tissues had chromosomal distributions and functional enrichment of correlated genes differing from those of their normal tissue counterparts. The GO analysis of network underlying the genes correlated with DNAme alteration and differentially expressed genes (DEGs) shows functional clusters centred on immune cell function and muscle system processes. In KEGG analysis, only the calcium signalling pathway was enriched either by the genes correlated with changes in DNAme or DEGs. The protein-protein interactions (PPI) underlying the genes altered at both the DNAme and transcriptional highlighted two important functional clusters. One of these was related to the immune response and had the estrogen receptor-encoding ESR1 gene as its node. The other cluster comprised cardiac electrophysiology-related genes. Intelliectin-1 (ITLN1), a component of the innate immune system, was transcriptionally downregulated in HCM and had a hypermethylated site within 1500 bp upstream of the ITLN1 transcription start site. Estimates of immune infiltration demonstrated a relative decline in immune cell population diversity in HCM. A combination of DNAme and transcriptome profiles may help identify and develop new therapeutic targets for HCM.
Subject(s)
Cardiomyopathy, Hypertrophic , Epigenome , Humans , DNA Methylation , Gene Expression Profiling , Cardiomyopathy, Hypertrophic/genetics , Cardiomyopathy, Hypertrophic/metabolism , Transcriptome , ElectrophysiologyABSTRACT
OBJECTIVE: To explore the correlation between clinical phenotypes and pathogenic variants in two patients with familial hypercholesterolemia. METHODS: Both patients were subjected to whole exome sequencing (WES) with a focus on the analysis of genes associated with dyslipidemia. Candidate variants were verified by Sanger sequencing of the patients and their family members. RESULTS: WES revealed that the proband 1 has harbored two heterozygous variants of the LDLR gene, namely c.1360G>A (p.D454N) and c.292G>A (p.G98S), whilst proband 2 has harbored a heterozygous c.321T>G (p.C107W) variant of the LDLR gene. Based on the guidelines from the American College of Medical Genetic and Genomics (ACMG), the above variants were respectively predicted to be likely pathogenic (PM1+PM2+PP2+PP3+PP4+PP5), variant of unknown significance (PM1+PP2+PP3), and likely pathogenic (PM1+PM2+PP2+PP4+PP5). Treatment with PCSK9 inhibitor has attained a significant effect in proband 1 but no apparent effect in proband 2. CONCLUSION: Variants of the LDLR gene probably underlay the familial hypercholesterolemia in the two pedigrees. The difference in the severity of the clinical phenotypes and response to PCSK9 inhibitor treatment between the two probands may be attributed to the different genotypes of the LDLR gene. Genetic testing not only can provide a basis for clinical diagnosis, but also facilitate the choice of lipid-lowering drugs.
Subject(s)
Hyperlipoproteinemia Type II , Receptors, LDL , Humans , China , Hyperlipoproteinemia Type II/genetics , Phenotype , Receptors, LDL/geneticsABSTRACT
Background and aim: Takayasu's arteritis (TA) is a chronic inflammation that frequently involves the aorta and its major branches. It has been known that atherosclerosis can occur in some TA patients. Objectives: This study aimed to identify the risk factors associated with the development of atherosclerosis in TA. Methods: This retrospective study enrolled a total of 101 TA patients. All patients were divided into two groups according to the absence or presence of atherosclerosis. Baseline demographic features and clinical characteristics were compared between two groups. A logistic model was applied to determine the risk factors associated with the development of atherosclerosis. Results: Our data suggested that the disease duration of patients in the atherosclerosis group was significantly longer than that of patients in the non-atherosclerosis group [96(18.00, 180.00) versus 48.00(12.00, 111.00) months] (P = .015). In addition, the average age of patients with atherosclerosis was significantly older compared to patients without atherosclerosis [44.00(38.00, 48.00)versus 28.50(24.00ï¼37.00)years] (P < .001). Logistic regression analysis showed that the risk of developing atherosclerosis increased by 9.2% per 1 year increase in the disease duration (P = .005, OR 1.092, 95%CI: 1.027-1.162). Patients with TG/HDL-C ratio more than 0.8875 were associated with a 5.861fold increase of risk developing atherosclerosis (P < .001, OR 5.861, 95%CI: 2.299-14.939). Conclusion: Our study indicated that prolonged disease duration and elevated TG/HDL-C ratio are associated with the development of atherosclerosis in TA patients.
Subject(s)
Atherosclerosis , Takayasu Arteritis , Aorta , Atherosclerosis/etiology , Humans , Retrospective Studies , Risk Factors , Takayasu Arteritis/complicationsABSTRACT
Background: Saphenous veins are regular bypass conduits selected in non-left anterior descending artery (LAD) coronary artery bypass graft (CABG) surgery. Despite the technical errors, acute thrombosis, intimal hyperplasia and arteriosclerosis which could lead to saphenous vein graft (SVG) failure, the metal-clipping-related SVG failure is unique and rare. This study was conducted to investigate the clinical and underlying mechanisms of the metal-clipping-related SVG failure. Methods: We collected 6 typical cases of the metal-clipping-related SVG failure in 41 patients who were diagnosed graft stenosis by coronary angiograph after CABG in the Department of Cardiology, Beijing Anzhen Hospital, from January 2020 to September 2021. Furthermore, we built an in vitro model to verify the identical intravascular ultrasound (IVUS) pattern of metal clip. Results: There were 6 in 41 cases of SVG stenosis caused by clipping of the side branches. We found that the stenosis of SVG caused by metal clipping mostly occurred at the corner and multipole clipping points. In this situation, great resistance could be felt when pushing the instruments through the stenosis and crystallized cholesterol was rarely caught by the distal protection device. We verified the similar IVUS pattern of metal clip at the side-branches of SVG in vitro. Conclusions: The metal-clipping-related stenosis may lead to SVG failure. The stenosis of SVG caused by metal clipping mostly occurred at the corner and multipole clipping points. IVUS showed great modality for clarification.
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It has been convincingly demonstrated that remote ischemic preconditioning (RIPC) can make the myocardium resistant to the subsequent ischemia reperfusion injury (IRI), which causes severe damages by mainly generating cell death. However, the cardioprotective effects of the hepatic RIPC, which is the largest metabolic organ against I/R, have not been fully studied. The aim of our research is whether remote liver RIPC may provide cardioprotective effects against the I/R-induced injury. Here, we generated an I/R mice model in four groups to analyze the effect. The control group is the isolated hearts with 140-min perfusion. I/R group added ischemia in 30 min following 90-min reperfusion. The third group (sham) was subjected to the same procedure as the latter group. The animals in the fourth group selected as the treatment group, underwent a hepatic RIPC by three cycles of 5-min occlusion of the portal triad and then followed by induction of I/R in the isolated heart. The level of myocardial infarction and the preventive effects of RIPC were assessed by pathological characteristics, namely, infarct, enzyme releases, pressure, and cardiac mechanical activity. Subjected to I/R, the hepatic RIPC minimized the infarct size (17.7 ± 4.96 vs. 50.06 ± 5, p < 0.001) and improved the left ventricular-developed pressure (from 47.42 ± 6.27 to 91.62 ± 5.22 mmHg) and the mechanical activity. Release of phosphocreatine kinase-myocardial band (73.86 ± 1.95 vs. 25.93 ± 0.66 IUL-1) and lactate dehydrogenase (299.01 ± 10.7 vs. 152.3 ± 16.7 IUL-1) was also decreased in the RIPC-treated group. These results demonstrate the cardioprotective effects of the hepatic remote preconditioning against the injury caused by I/R in the isolated perfused hearts.
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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.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Interferon-gamma/metabolism , Takayasu Arteritis/immunology , Adult , Cells, Cultured , Female , Humans , Interferon-gamma/genetics , Male , Middle Aged , Takayasu Arteritis/bloodABSTRACT
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.
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Prehypertension is a risk factor for cardiovascular disease (CVD) and all-cause mortality. However, it is unclear whether prehypertension combined with diabetes associate with a higher risk for cardiovascular disease and all-cause mortality. The purpose of this study was to explore the relationship between prehypertension and the risk of CVD and all-cause mortality was different among individuals with or without diabetes. In the prospective community-based Kailuan study, 67 344 participants without hypertension or a history of CVD at baseline (2006) were included. Prehypertension was defined as systolic blood pressure of 120-139 mmHg or diastolic blood pressure of 80-89 mmHg. The outcomes were CVD and all-cause mortality were followed up through December 31, 2017. We performed Cox proportional hazards models to evaluate the relationships between prehypertension and CVD and all-cause mortality by diabetes status. During a median follow-up of 11.03 years, 2981 CVD events and 4655 all-cause mortality occurred. After adjusting age, sex, and other factors, the associations of prehypertension with risk of CVD and all-cause mortality were significant in participants without diabetes (hazard ratio and 95% confidence interval: 1.54 [1.38-1.71] and 1.27 [1.17-1.38]), but not in participants with diabetes (1.20 [0.93-1.56] and 0.88 [0.73-1.07]). The interactions between prehypertension and diabetes for the risk of CVD and all-cause mortality were all significant (all p < .05). Prehypertension was only associated with an increased risk for CVD and all-cause mortality in non-diabetes participants. Diabetes modifies the relation of prehypertension with the risk of CVD and all-cause mortality.
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus , Hypertension , Prehypertension , Blood Pressure , Cardiovascular Diseases/epidemiology , Humans , Prehypertension/epidemiology , Proportional Hazards Models , Prospective Studies , Risk FactorsABSTRACT
OBJECTIVE: This study aimed to investigate the imaging and serological features in Takayasu arteritis (TA) patients with valvular involvement and determine the relationship between them. METHOD: This is a retrospective single-center study enrolled 103 TA patients fulfilling the American College of Rheumatology criteria. An independent medical chart review was performed by two senior rheumatologists from Beijing Anzhen Hospital, Capital Medical University. The logistic analysis was used to investigate the relationship between valvular involvement in TA patients and the imaging and serological features of them. RESULTS: Sixty-six TA patients (64.08%) had cardiac valvular involvement in our study. Aortic insufficiency (62.12%) was the most common valvular involvement. Twelve (22.22%) patients developed heart failure. In patients with valvular involvement, the most common angiographic type was Numano type V, which was significantly higher than that in patients without valvular involvement (53.30% vs 32.43%, p = 0.044), followed by coronary involvement (28.79% vs 10.81%, p = 0.036) and Numano type IIb (21.21% vs 5.41%, p = 0.034). Serum levels of immunoglobulin A (2.84 ± 1.42 g/L vs 2.26 ± 0.97 g/L, p = 0.032) and immunoglobulin G (13.5 ± 4.71 g/L vs 11.42 ± 3.01 g/L, p = 0.015) were significantly higher in patients with valvular involvement. Numano type IIb is significantly related to moderate-severe aortic valvular regurgitation in TA patients (4.10 [1.03-16.33], p = 0.04). Elevated C-reactive protein (CRP) level is associated with moderate-severe mitral valve involvement in TA patients (p = 0.05, OR = 17.75, 95% CI 1.07-295.41). CONCLUSIONS: CRP elevation and Numano type IIb are significantly related to different types of valvular involvement in TA patients. Key Points ⢠The Numano types IIb and V were common in TA patients with valvular involvement. ⢠CRP elevation and Numano type IIb are close related to valvular involvement in TA patient. ⢠Echocardiogram screening and CRP level examination are reasonable to TA patients which might have valvular involvement.
Subject(s)
Aortic Valve Insufficiency , Takayasu Arteritis , Aortic Valve Insufficiency/diagnostic imaging , Echocardiography , Heart , Humans , Retrospective Studies , Takayasu Arteritis/complications , Takayasu Arteritis/diagnostic imagingABSTRACT
BACKGROUND: The etiology of Takayasu arteritis (TA) is unknown; however, a possible relationship between streptococcal infection and TA has been proposed. This study aimed to identify the clinical features and cardiac valvular involvement in untreated TA patients with an elevated antistreptolysin O (ASO) titer. METHODS: In this retrospective study, the clinical characteristics and features of valvular involvement were compared in TA patients with or without an elevated ASO titer. RESULTS: Of the 74 untreated TA patients, 13 patients were found have elevated ASO titers (17.6%). Mitral insufficiency was the most common in patients with elevated ASO (69.2%, 9/13), followed by aortic valve insufficiency (46.2%, 5/13) and tricuspid insufficiency (46.2%, 5/13), which were no significantly different than that in normal ASO group. The proportions of moderate to severe mitral (30.8% vs 1.6%, p = 0.000) and tricuspid valve (15.4% vs 1.64%, p = 0.023) insufficiency in the ASO positive group were significantly higher than those in the ASO negative group. The odds of mitral regurgitation in patients with elevated ASO titers were 3.9 times higher than those in the group with normal ASO titers (p = 0.053, OR = 3.929, 95% confidence interval [CI]: 0.983-15.694). Furthermore, the risk of moderate to severe mitral insufficiency in patients with elevated ASO titers was 41.6 times higher than that in patients with normal ASO titers (p = 0.002, OR = 41.600, 95% CI: 3.867-447.559). CONCLUSIONS: An increase in ASO titer is related to valvular involvement in TA and is closely linked to mitral insufficiency.
Subject(s)
Antistreptolysin/blood , Mitral Valve Insufficiency/blood , Takayasu Arteritis/blood , Adult , Biomarkers/blood , Female , Humans , Male , Middle Aged , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/etiology , Retrospective Studies , Risk Factors , Takayasu Arteritis/complications , Takayasu Arteritis/diagnosis , Up-Regulation , Young AdultABSTRACT
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.
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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.
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BACKGROUND: We sought to analyze the pathological characteristics of hypertrophic obstructive cardiomyopathy (HOCM) with concomitant mitral valve abnormalities and to discuss the surgical treatment strategies. METHODS: The clinical data of 26 HOCM patients treated from January 2014 to March 2016 were retrospectively analyzed. There were 19 males and 7 females with a mean age of 47 ± 16 years (range, 10-70 years). Echocardiography showed HOCM, systolic anterior motion of the mitral apparatus, and concomitant mitral regurgitation. Modified Morrow procedure with expanded resection area was performed in 21 patients. Concomitant mitral valvuloplasty was performed in 4 patients, coronary artery bypass grafting was performed in one patient, and aortic valve replacement was performed in one patient. Echocardiography was performed intraoperatively at postoperative 1 week and at postoperative 1 year to evaluate the left ventricular obstruction and the mitral regurgitation. RESULTS: The left ventricular outflow tract gradient, left ventricular outflow tract velocity, septal thickness, and mitral regurgitation area decreased significantly at postoperative 1 week and 1 year in comparison with the baseline (all P < .001). The postoperative mitral regurgitation and systolic anterior motion of the mitral apparatus were completely abolished or significantly relieved. Only one patient had moderate mitral regurgitation of 7 cm2 after the surgery. At postoperative 1 year, all patients were asymptomatic, and the quality of life was significantly improved. The New York Heart Association (NYHA) class was I-II. Echocardiography showed good anatomy and function of the mitral valve. CONCLUSIONS: Concomitant mitral valve abnormality is not uncommon in HOCM. Septal myectomy can adequately expand the left ventricular outflow tract and abolish mitral regurgitation and systolic anterior motion of the mitral apparatus. Concomitant mitral valvuloplasty is indicated for severe congenital abnormalities or secondary lesions of the mitral valve, and the outcomes are satisfactory.
Subject(s)
Cardiomyopathy, Hypertrophic/complications , Cardiomyopathy, Hypertrophic/surgery , Mitral Valve Insufficiency/complications , Mitral Valve Insufficiency/surgery , Adolescent , Adult , Aged , Cardiac Surgical Procedures/methods , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cardiomyopathy, Hypertrophic/pathology , Child , Echocardiography , Female , Humans , Male , Middle Aged , Mitral Valve/diagnostic imaging , Mitral Valve/physiopathology , Mitral Valve/surgery , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/physiopathology , Retrospective Studies , Ultrasonography, Doppler , Young AdultABSTRACT
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.
Subject(s)
Endoplasmic Reticulum Stress/drug effects , Inflammation/genetics , Insulin Resistance/genetics , Lipid Metabolism/genetics , Liver/drug effects , Non-alcoholic Fatty Liver Disease/prevention & control , Stilbenes/therapeutic use , Animals , Diet, High-Fat , Dyslipidemias/genetics , Dyslipidemias/metabolism , Dyslipidemias/prevention & control , Gene Expression/drug effects , Liver/metabolism , Male , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Phytotherapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Rats, Sprague-Dawley , Resveratrol , Stilbenes/pharmacologyABSTRACT
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.