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1.
Biochim Biophys Acta Mol Basis Dis ; 1869(2): 166619, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36494038

RESUMO

Thoracic aortic aneurysm/dissection (TAAD) is a life-threatening cardiovascular disorder. Endoplasmic reticulum stress (ERS) and vascular smooth muscle cell (VSMC) apoptosis are involved in TAAD progression. The Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) pathway is associated with VSMC apoptosis. Serum Angiopoietin-Like Protein 8 (ANGPTL8) levels are associated with aortic diameter and rupture rate of TAAD. However, a direct role of ANGPTL8 in TAAD has not been determined. ß-Aminopropionitrile monofumarate (BAPN) was used to induce TAAD in C57BL/6 mice. ANGPTL8 knockout mice were used to detect the effects of ANGPTL8 on TAAD development. ANGPTL8knockdown in vitro was used to analyze the role of ANGPTL8 in VSMCs and ERS. In addition, over-expression of ANGPTL8 in VSMCs and a PERK inhibitor were used to assess the effect of ANGPTL8 on the PERK pathway. ANGPTL8 levels were increased in the aortic wall and VSMCs of BAPN-induced TAAD mice. Compared with BAPN-treated wild-type mice, ANGPTL8 knockout significantly reduced the rupture rate of TAAD to 0 %. In addition, the protein levels of proinflammatory cytokines and matrix metalloproteinase 9 (MMP9) and ERS proteins were decreased in the aorta wall. Angptl8 shRNA decreased MMP9 and ERS protein levels in VSMCs in vitro. Overexpression of ANGPTL8 significantly increased the levels of ERS proteins and MMPs, while a PERK inhibitor significantly decreased the effects of ANGPTL8 in VSMCs. ANGPTL8 contributed to TAAD development by inducing ERS activation and degradation of extracellular matrix in the aorta wall. Inhibition of ANGPTL8 may therefore represent a new strategy for TAAD therapy.


Assuntos
Proteína 8 Semelhante a Angiopoietina , Aneurisma da Aorta Torácica , Dissecção Aórtica , Animais , Camundongos , Aminopropionitrilo , Proteína 8 Semelhante a Angiopoietina/genética , Aneurisma da Aorta Torácica/induzido quimicamente , Aneurisma da Aorta Torácica/genética , Dissecção Aórtica/induzido quimicamente , Dissecção Aórtica/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout
2.
Biochem Pharmacol ; 186: 114502, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33684391

RESUMO

OBJECTIVE: Obstructive sleep apnea (OSA) is a major risk factor for cardiovascular mortality. Apnea-induced chronic intermittent hypoxia (CIH) is a primary pathophysiological manifestation of OSA that promotes various cardiovascular alterations, such as aortic vascular remodeling. In this study, we investigated the association between angiopoietin-like proteins 8 (ANGPTL8) and CIH-induced aortic vascular remodeling in mice. METHODS: C57BL/6J male mice were divided into four groups: Normoxia group, ANGPTL8-/- group, CIH group, CIH + ANGPTL8-/- group. Mice in the normoxia group and ANGPTL8-/- group received no treatment, while mice in the CIH and CIH + ANGPTL8-/- group were subjected to CIH (21%-5% O2, 180 s/cycle, 10 h/day) for 6 weeks. At the end of the experiments, intima-media thickness (IMT), elastin disorganization, and aortic wall collagen abundance were assessed in vivo. Immunohistochemistry and Western-blot were used to detect endoplasmic reticulum stress (ERS) and aortic vascular smooth muscle cell proliferation. ANGPTL8 shRNA and ANGPL8 overexpression were used in aortic vascular smooth muscle cells to investigate the mechanism of ANGPTL8 in CIH. RESULTS: Compared to the control group, CIH exposure significantly increased intima-media thickness (IMT), elastic fibers disorganization, and aortic wall collagen abundance. CIH also significantly increased blood pressure, induced hyperlipidemia, as well as the expression of ERS protein activating transcription factor-6 (ATF6) and aortic vascular smooth muscle cell proliferation. Contrary, ANGPTL8-/- significantly mitigated the CIH-induced vascular remodeling; ANGPTL8-/- decreased CIH-induced hypertension and hyperlipidemia, inhibited the protein expression of ATF6, and aortic vascular smooth muscle cell proliferation. Moreover, our in vitro study suggested that CIH could induce ANGPTL8 expression via hypoxia-inducible factor (HIF-1α); ANGPTL8 induced proliferation of aortic vascular smooth muscle cells via the ERS pathway. CONCLUSION: ANGPTL8-/- can prevent CIH-induced aortic vascular remodeling, probably through the inhibition of the ERS pathway. Therefore, ANGPTL8 might be a potential target in CIH-induced aortic vascular remodeling.


Assuntos
Proteínas Semelhantes a Angiopoietina/deficiência , Modelos Animais de Doenças , Hipóxia/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Remodelação Vascular/fisiologia , Proteína 8 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina/genética , Animais , Células Cultivadas , Feminino , Humanos , Hipóxia/complicações , Hipóxia/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Gravidez , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/genética
3.
Clin Chim Acta ; 508: 161-169, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32417211

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is the most common type of sleep breathing disorder and is characterized by chronic intermittent hypoxia, which could cause inflammation and nuclear factor kappa B (NF-KB)-dependent inflammatory pathways activation. Circulating APRIL (a proliferation-inducing ligand) play an important role in promoting inflammation and NF-KB-dependent inflammatory pathways activation. We explored the role of APRIL as a potential mechanism of inflammation in OSA patients. METHODS: After detailed sleep evaluated, venous blood and demographic data were collected from 155 subjects with varying severity of OSA and 52 control subjects. Plasma levels of APRIL were measured by human Magnetic Luminex assay. RESULTS: Plasma APRIL levels were significantly higher in OSA subjects compared with control subjects. Categorization of the OSA subjects into mild, moderate, and severe OSA subgroups found that plasma levels of APRIL increased with the severity of OSA. After adjusting confounding factors, found that increased plasma APRIL levels were conferred a higher odds ratio of OSA. Moreover, plasma APRIL levels were positively associated with the apnea-hypopnea index, which represents the severity of OSA. Furthermore, plasma APRIL showed higher discriminatory accuracy in predicting the presence of OSA. CONCLUSIONS: Plasma APRIL levels were significantly associated with the occurrence of OSA and its severity. APRIL could be a plasma biomarker with a positive diagnostic value for inflammation and NF-KB-dependent inflammatory pathways activation in subjects with OSA. TRIAL REGISTRATION: The project was approved by the Chinese Clinical Trial Registry (No. ChiCTRROC-17011027).


Assuntos
Apneia Obstrutiva do Sono , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Adulto , Biomarcadores , China , Humanos
4.
Eur J Vasc Endovasc Surg ; 59(6): 1000-1010, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31879145

RESUMO

OBJECTIVE: Thoracic aortic dissection (TAD) has a high mortality rate. Intermittent hypoxia (IH) triggers both harmful and beneficial effects in numerous physiological systems. The effects of IH on TAD development were explored in a mouse model. METHODS: ß-Aminopropionitrile monofumarate (BAPN) was used to induce TAD in C57BL/6 mice. Three week old male mice were treated with 1 g/kg/day BAPN in drinking water for four weeks and simultaneously subjected to IH (n = 30) (21%-5% O2, 90 s/cycle, 10 h/day, IH + BAPN group) or normoxia (n = 30) (21% O2, 24 h/day, BAPN group). Human VSMCs (HUASMCs) exposed to IH (30 min, 5% O2)/re-oxygenation (30 min, 21% O2) cycles with a maximum of 60 min/cycle to detect the effect of IH on HIF-1α and LOX via HIF-1α-siRNA. RESULTS: It was found that BAPN administration significantly increased the lumen size and wall thickness of aortas compared with the normal group, but was significantly reversed by IH exposure. Additionally, IH exposure significantly increased the survival rate of BAPN induced TAD (70% vs. 40%). Furthermore, IH exposure reduced BAPN induced elastin breaks and apoptosis of vascular smooth muscle cells. IH exposure also reversed BAPN induced upregulation of inflammation and extracellular matrix (ECM) degradation. Real time polymerase chain reaction (RT-PCR) confirmed that IH inhibited inflammation and ECM degradation related genes interleukin (IL)-1ß, IL-6, cathepsin S (Cat S), and matrix metalloproteinase 9 (MMP-9), but upregulated the ECM synthesis related genes lysyl oxidase (LOX) and collagen type I alpha2 (Col1a2) compared with the BAPN group. In vitro results suggest that IH promotes the expression of LOX via HIF-1α. CONCLUSION: The results suggest that IH alleviates BAPN induced TAD in C57BL/6 mice.


Assuntos
Aorta Torácica/fisiopatologia , Aneurisma da Aorta Torácica/terapia , Dissecção Aórtica/terapia , Hipóxia/fisiopatologia , Pós-Condicionamento Isquêmico/métodos , Aminopropionitrilo/análogos & derivados , Aminopropionitrilo/toxicidade , Dissecção Aórtica/etiologia , Animais , Aorta Torácica/citologia , Aorta Torácica/efeitos dos fármacos , Aneurisma da Aorta Torácica/induzido quimicamente , Aneurisma da Aorta Torácica/complicações , Modelos Animais de Doenças , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
5.
Biomed Res Int ; 2019: 5907361, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737670

RESUMO

OBJECTIVES: Obstructive sleep apnea (OSA) is a common disorder influenced by genetic and environmental factors. Mutations of AT-hook DNA-binding motif containing 1 (AHDC1) gene have been implicated which could cause rare syndromes presenting OSA. This study aims to investigate some rare mutations of AHDC1 in Chinese Han individuals with OSA. PATIENTS AND METHODS: Three hundred and seventy-five patients with OSA and one hundred and nine control individuals underwent polysomnography. A targeted sequencing experiment was taken in 100 patients with moderate-to-severe OSA, and genotyping was taken in 157 moderate-to-severe OSA and 100 control individuals. The effect of mutations was validated by the luciferase reporter assay. RESULTS: One rare missense mutation (AHDC1: p.G1484D) and two mutations (c.-88C>T; c.-781C>G) in 5'-untranslated region (UTR) of AHDC1 were identified. The rare mutation (c.-781C>G) in 5'-UTR that was identified in several patients presenting more severe clinical manifestations affects expression of AHDC1. Conclusions. Our results revealed three rare mutations of AHDC1 in patients with OSA in Chinese Hanindividuals.


Assuntos
Proteínas de Ligação a DNA/genética , Mutação/genética , Apneia Obstrutiva do Sono/genética , Povo Asiático/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia/métodos
6.
Huan Jing Ke Xue ; 40(5): 2152-2159, 2019 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087851

RESUMO

To understand the difference between transport coefficients of water runoff, sand discharge, and phosphorus flux in each subsection of a river, a judgement method for analyzing the characteristics of phosphorus transport and transformation in water of rivers was established in this study. Based on the measured data of water runoff, sand discharge, and phosphorus fraction concentrations in the water of the Three Gorges Reservoir (TGR) in January and July 2015, characteristics of phosphorus transport and transformation in the water were analyzed by using the conceptual method. The results showed that the predominant phosphorus fraction in water of the TGR was total dissolved phosphorus (TDP), which accounted for 51%-96% of total phosphorus in water. The TDP flux relative to runoff in the TGR decreased in January 2015 That was caused by the adsorption of TDP by suspended particles in the dry season. In contrast, TDP flux showed additive effect relative to water runoff in July 2015 due to exogenous water inputs with high TDP concentrations in the wet season. Both sand and total particulate phosphorus (TPP) presence in the water showed obvious sediment and retention characteristics during the two periods. The TPP flux presented an additive effect relative to sand discharge, meaning that the major transformation direction of phosphorus fractions was from TDP to TPP. The subsection between Qingxichang and Wanzhou was the main retention area of water, sand, and phosphorus in the TGR, which can be associated with the enhancement of phosphorus adsorption capacity caused by particle size reduction of suspended particles in the subsection.

7.
Sleep Breath ; 23(1): 77-86, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29682699

RESUMO

PURPOSE: Obstructive sleep apnea (OSA) is associated with increased levels of systemic inflammatory markers, increased arterial stiffness, and endothelial dysfunction, which may lead to increased cardiovascular risk. We aimed to quantify the effects of continuous positive airway pressure (CPAP) on cardiovascular biomarkers and to establish predictors of response to CPAP. METHODS: We searched PubMed and the Cochrane Library from inception to May 31, 2017. Randomized controlled trials (RCTs) assessing the efficacy of CPAP on high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumor necrosis factor- alpha (TNF-α), augmentation index (AIx), pulse wave velocity (PWV), and flow-mediated dilatation (FMD) in patients with OSA were selected by consensus. RESULTS: We included 15 RCTs comprising 1090 patients in the meta-analysis. The pooled standard mean difference (SMD) of effect of CPAP on hs-CRP was - 0.64 (95% confidence interval (CI) - 1.19 to - 0.09; P = 0.02). CPAP was associated with a reduction in AIx of 1.53% (95% CI, 0.80 to 2.26%; P < 0.001) and a significant increase in FMD of 3.96% (95% CI 1.34 to 6.59%; P = 0.003). Subgroup analyses found CPAP was likely to be more effective in improving FMD levels in severe OSA patients or patients with effective CPAP use ≥ 4 h/night. CONCLUSIONS: Among patients with OSA, CPAP improves inflammatory marker hs-CRP, arterial stiffness marker AIx, and endothelial function marker FMD. These biomarkers may provide information related to response to treatment. Future studies will need to clarify the efficacy of these biomarkers in assessing cardiovascular risk reduction among OSA treated with CPAP.


Assuntos
Sistema Cardiovascular/metabolismo , Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono/terapia , Rigidez Vascular/fisiologia , Biomarcadores/metabolismo , Sistema Cardiovascular/fisiopatologia , Humanos , Polissonografia , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Clin Chim Acta ; 490: 39-45, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30562485

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) was characterized by chronic intermittent hypoxia, which was an independent risk factor for endothelial dysfunction. Circulating TNFRSF11B might play an important role in promoting endothelial cells dysfunction. We explored the role of plasma TNFRSF11B as a potential mechanism of endothelial dysfunction in OSA patients. METHODS: The study population consisted of 120 patients with varying severity of OSA and 40 control subjects. Plasma TNFRSF11B levels were measured using human Magnetic Luminex assay. RESULTS: Our data showed that plasma TNFRSF11B levels were significantly higher in patients with OSA. After adjusting confounding factors, plasma TNFRSF11B levels were independently associated with the presence of OSA (Beta:0.434, 95% CI: 664.096 to 1076.247; P < 0.001) and plasma TNFRSF11B levels were positively associated with the apnea-hypopnea index (Beta:0.486, 95% CI: 0.007 to 0.017; P < 0.001). Furthermore, plasma TNFRSF11B showed higher discriminatory accuracy in predicting the presence of OSA (AUC:0.964). CONCLUSIONS: Plasma TNFRSF11B levels were significantly associated with the presence of OSA and its severity. TNFRSF11B could be a plasma biomarker with a positive diagnostic value for premature vascular endothelial dysfunction in patients with OSA.


Assuntos
Osteoprotegerina/sangue , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/diagnóstico , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteoglicanas/sangue
9.
Huan Jing Ke Xue ; 39(5): 2165-2173, 2018 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965516

RESUMO

In recent years, the total phosphorus pollution in Minjiang River was serious, and the surface sediments of the Minjiang River also threatened water quality. To study the spatial distributions of phosphorus in the surface sediments of the Minjiang River, samples of surface sediments were collected upstream (Aba District) and downstream (Yibin District) of the Minjiang River in December, 2016. The sediments were analyzed with the modified sequential extraction method (SEDEX) to obtain six forms of phosphorus, including exchangeable phosphorus (Ex-P), exchangeable organic phosphorus (Org-P), iron-bound phosphorus (Fe-P), authigenic phosphorus (Ca-P), detrital phosphorus (De-P), and refractory phosphorus (Res-P). The results indicated that the contents of total phosphorus (TP) in surface sediments ranged from 522.17 µg ·g-1 to 979.22 µg ·g-1, which were far more than the soil phosphorus background values (700 µg ·g-1). The spatial distribution characteristics of the TP of surface sediments indicated that the TP concentrations in sediments at the Meishan sections (the middle reach of the Minjiang River) were higher than those in the other sections. This was related to the smaller particle size and higher OM contents in sediments in the Meishan sections. The main phosphorus forms in the sediments in the Minjiang River were Ca-P and De-P, with their concentrations accounting for 75% of TP in the sediments. The bio-available phosphorus, which included Ex-P, Org-P, and Fe-P, accounted for 0.31%-29.62% of TP in the sediments of the Minjiang River. The concentrations of bio-available phosphorus in sediments at the Meishan sections and Leshan sections (the middle reach) were highest, indicating that bio-available phosphorus in the surface sediments was high, and its potential environmental impact risks were higher.

10.
Sheng Li Xue Bao ; 70(2): 141-148, 2018 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-29691578

RESUMO

It has been recognized that patients with hypothyroidism have higher risks of atherosclerosis and coronary heart disease, however, the mechanisms are largely unknown. Considering that macrophage dysfunction plays an important role in the formation and development of atherosclerosis plaques, this study aimed to investigate the direct effects of thyroid hormone on macrophage functions and to provide new insight for the mechanism of hypothyroid atherosclerosis. RAW264.7 cells (mouse leukaemic monocyte macrophage cell line) were incubated with oxidized low-density lipoprotein (oxLDL) to establish macrophage foam cells model in vitro, and the protective effects of different concentration of thyroxine (T4) on the macrophage foam cells function were explored. The proliferation, migration and cell aging of macrophages were detected by MTT method, scratch test and ß-galactosidase staining respectively. The ELISA method was used to detect the secretion of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-1ß (IL-1ß). Western blot analysis was applied to measure the phosphorylation of focal adhesion kinase (FAK), which was required for the process of proliferation and migration of macrophages. The results showed that oxLDL significantly inhibited the macrophage proliferation and migration, induced cell senescence, and promoted the secretion of TNF-α, MCP-1, and IL-1ß; while T4 reversed those effects of oxLDL on macrophage in a concentration-dependent manner. Moreover, oxLDL increased the phosphorylation of FAK in macrophage, while T4 concentration-dependently reversed the effect. These results suggest that T4 modulates macrophage proliferation, migration, senescence, and secretion of inflammation factors in a concentration-dependent way.


Assuntos
Células Espumosas/efeitos dos fármacos , Lipoproteínas LDL/efeitos adversos , Macrófagos/efeitos dos fármacos , Tiroxina/farmacologia , Animais , Aterosclerose , Quimiocina CCL2/metabolismo , Células Espumosas/patologia , Quinase 1 de Adesão Focal/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/patologia , Camundongos , Fosforilação , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo
11.
Biomed Environ Sci ; 29(10): 713-723, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27927271

RESUMO

OBJECTIVE: This study is aimed at observing the role of long noncoding RNAs (lncRNAs) in the pathogenesis of abdominal aortic aneurysm (AAA). METHODS: LncRNA and mRNA expression signatures of AAA tissues and normal abdominal aortic tissues (NT) were analyzed by microarray and further verified by Real-time quantitative reverse-transcription PCR (qRT-PCR). The lncRNAs-mRNAs targeting relationships were identified using computational analysis. The effect of lnc-ARG on 5-lipoxygenase (ALOX5) expression was tested in HeLa cells. RESULTS: Differential expressions of 3,688 lncRNAs and 3,007 mRNAs were identified between AAA and NT tissues. Moreover, 1,284 differentially expressed long intergenic noncoding RNAs and 206 differentially expressed enhancer-like lncRNAs adjacent to protein-coding genes were discerned by bioinformatics analysis. Some differentially expressed lncRNAs and mRNAs between AAA and normal tissue samples were further verified using qRT-PCR. A co-expression network of coding and noncoding genes was constructed based on the correlation analysis between the differentially expressed lncRNAs and mRNAs. In addition, the lnc-ARG located within the upstream of ALOX5 was sorted as a noncoding transcript by analyzing the protein-coding potential using computational analysis. Furthermore, we found that lnc-ARG can decrease the mRNA level of ALOX5 and reactive oxygen species production in HeLa cells. CONCLUSION: This study revealed new lncRNA candidates are related to the pathogenesis of AAA.


Assuntos
Aneurisma da Aorta Abdominal/genética , RNA Longo não Codificante/genética , Idoso , Aneurisma da Aorta Abdominal/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA Longo não Codificante/metabolismo
12.
Huan Jing Ke Xue ; 37(5): 1677-84, 2016 May 15.
Artigo em Chinês | MEDLINE | ID: mdl-27506019

RESUMO

Based on the monitoring data in the tidal reach and estuary of the Daliao river in August and November, 2013, the seasonal and spatial distribution of the nitrogen and phosphorus forms were studied, and the degree of eutrophication was evaluated. The results showed that nitrate nitrogen was the main chemical species and occupied about fifty-five percent of inorganic nitrogen, and the particulate phosphorus was the main chemical species and occupied about fifty percent of total phosphorus in the tidal reach and estuary of the Daliao river in wet and dry seasons, 2013. The concentrations of nitrogen and phosphorus nutrients decreased in the direction from tidal reach to estuary of the Daliao river. Correlation analysis showed that there was a significant negative correlation between the nitrogen and phosphorus forms and salinity in most of the water body, which illustrated that physical dilution of seawater played a major role in the spatial distribution of nitrogen and phosphorus forms. The concentrations of nitrogen and phosphorus nutrients in the dry season were higher than those in the wet season, this was mainly related to the seasonal terrestrial input of the tidal reach. The concentration of the dissolved inorganic nitrogen was higher than 0.30 mg · L⁻¹, and the value of N/P was higher than 60, which indicated that PO4³â»-P was the nutrient limiting phytoplankton growth in the tidal reach and estuary of the Daliao river in August and November, 2013.


Assuntos
Estuários , Eutrofização , Nitrogênio/análise , Fósforo/análise , Rios/química , China , Nitratos/análise , Fitoplâncton , Estações do Ano , Água do Mar/química , Análise Espacial
13.
J Cardiovasc Pharmacol ; 67(5): 412-7, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26828321

RESUMO

Epidemiological studies have suggested that hypercholesterolemia is an independent determinant of increased left ventricular (LV) mass. Because high-density lipoprotein and its major protein apolipoprotein A-I (apoA-I) mediate reverse cholesterol transport (RCT) and have cardiac protective effects, we hypothesized that the apoA-I mimetic peptide D-4F could promote RCT in cardiac tissue and decrease cardiac hypertrophy induced by hypercholesterolemia. Low-density lipoprotein receptor-null mice were fed by a Western diet for 18 weeks and then randomized to receive water, or D-4F 0.3 mg/mL, or D-4F 0.5 mg/mL added to drinking water for 6 weeks. After D-4F administration, an increase in high-density lipoprotein cholesterol and a decrease in low-density lipoprotein cholesterol, total cholesterol, and triglyceride in a trend toward dose-responsivity were found in cardiac tissue. Ultrasound biomicroscopy revealed a reduction in LV posterior wall end-diastolic dimension, and an increase in mitral valve E/A ratio and LV ejection fraction. Hematoxylin-eosin staining showed reduced LV wall thickness and myocardial cell diameter. The protein levels of ABCA1 and LXRα were elevated in cardiac tissue of D-4F treated mice compared with the controls (P < 0.05). These results demonstrated that D-4F treatment reduced cardiac hypertrophy, and improved cardiac performance in low-density lipoprotein receptor-null mice fed a Western diet, presumably through the LXRα-ABCA1 pathway associated with enhanced myocardial RCT.


Assuntos
Apolipoproteína A-I/farmacologia , Cardiomegalia/fisiopatologia , Colesterol/metabolismo , Transportador 1 de Cassete de Ligação de ATP/biossíntese , Animais , Transporte Biológico , Cardiomegalia/etiologia , LDL-Colesterol/metabolismo , Dieta Ocidental , Feminino , Hipercolesterolemia/complicações , Receptores X do Fígado/biossíntese , Camundongos , Camundongos Knockout , Triglicerídeos/metabolismo
14.
Huan Jing Ke Xue ; 36(8): 2800-8, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26592006

RESUMO

Overall 20 surface water samples were collected from the Yangtze River, the Wangyu River and the Gonghu Bay (Lake Taihu) to clarify the pollution characteristics of nitrogen and phosphorus during 2 sample stages of "Water Transfers on Lake Taihu from the Yangtze River" in August and December of 2013 respectively. The results showed that the mass concentrations of NO2- -N, NO3- -N, NH4+ -N and TN in the Gonghu Bay were lower than those of the Yangtze River and Wangyu River during the 2 water transfer processes. However, there was higher level of DON content in the Gonghu Bay than that of the Yangtze River and Wangyu River. The percentages of various N species showed that NO3- -N was the major N species in the Yangtze River and Wangyu River during the 2 water transfer processes. TP contents in samples collected from the Yangtze River displayed a constant trend compared with the Wangyu River. However, the percentages of various P species were different with each other during the 2 water transfer processes. Mass concentrations of DON and TP in surface water in August were higher than those in December and the contents of NO3- -N and TDP were lower in August than those in December. In general, NO3- -N and TPP were the main N and P species in Wangyu River from the Yangtze River. NO3- -N, PO4(3-) -P and TPP were the main N and P species in Gonghu Bay from Wangyu River during the 2 water transfer processes.


Assuntos
Lagos/química , Rios/química , China , Água Doce/química , Nitrogênio/análise , Fósforo/análise , Poluentes Químicos da Água/análise
15.
J Pathol ; 236(3): 373-83, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25788370

RESUMO

Thoracic aortic aneurysm/dissection (TAAD) is characterized by excessive smooth muscle cell (SMC) loss, extracellular matrix (ECM) degradation and inflammation. In response to certain stimuli, endoplasmic reticulum (ER) stress is activated and regulates apoptosis and inflammation. Excessive apoptosis promotes aortic inflammation and degeneration, leading to TAAD. Therefore, we studied the role of ER stress in TAAD formation. A lysyl oxidase inhibitor, 3-aminopropionitrile fumarate (BAPN), was administrated to induce TAAD formation in mice, which showed significant SMC loss (α-SMA level). Excessive apoptosis (TUNEL staining) and ER stress (ATF4 and CHOP), along with inflammation, were present in TAAD samples from both mouse and human. Transcriptional profiling of SMCs after mechanical stress demonstrated the expression of genes for ER stress and inflammation. To explore the causal role of ER stress in initiating degenerative signalling events and TAAD, we treated wild-type (CHOP(+/+)) or CHOP(-/-) mice with BAPN and found that CHOP deficiency protected against TAAD formation and rupture, as well as reduction in α-SMA level. Both SMC apoptosis and inflammation were significantly reduced in CHOP(-/-) mice. Moreover, SMCs isolated from CHOP(-/-) mice were resistant to mechanical stress-induced apoptosis. Taken together, our results demonstrated that mechanical stress-induced ER stress promotes SMCs apoptosis, inflammation and degeneration, providing insight into TAAD formation and progression.


Assuntos
Aneurisma da Aorta Torácica/patologia , Apoptose , Estresse do Retículo Endoplasmático , Transdução de Sinais , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Aminopropionitrilo/farmacologia , Animais , Aorta/metabolismo , Aneurisma da Aorta Torácica/induzido quimicamente , Aneurisma da Aorta Torácica/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Humanos , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Miócitos de Músculo Liso/metabolismo , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo
16.
Huan Jing Ke Xue ; 36(11): 4013-20, 2015 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-26910985

RESUMO

A total of 13 surface water samples were collected from sewage outfalls and 3 main tributaries ( Hunhe River, Taizi River and Haicheng River) of the Daliao River to clarify the pollution characteristics of various species of nitrogen and phosphorus in July 2013, respectively. The results showed that the concentrations of DON in the Hunhe River, NO3(-)-N in the Taizi River, NH4(+) -N, PO4(3-) -P and DOP in the Haicheng River were higher than others. In water samples from the 3 main tributaries of the Daliao River, the TN and TP contents were above the national environmental quality standards for surface water (GB 3838-2002, grade V) except for the TP that was classified as grade IV in the Taizi River. The percentages of various N species showed that NO3(-) -N was the major N species in the Taizi River and Haicheng River, meanwhile DON was the major N species in the Hunhe River. The percentages of various P species showed that TPP was the major P species in the Hunhe River and Taizi River, and DOP was the major P species in the Haicheng River. TN content was above the national environmental quality standards for surface water (GB 3838-2002, grade V) in sewage outfalls. But TP content was classified as grade IV to above grade V. And the concentrations of NH4(+) -N, TN and TP in sewage outfalls of Shachang and Gangjian were higher than those in other sewage outfalls. The percentages of various N species in sewage outfalls showed that DIN was the major N species in sewage outfalls. There were higher level of TN and TP content in the Daliao River than those of tribtaries, and NO3(-) -N and TPP were the major N and P species, respectively. In general, the nutrients analysis of tributaries, sewage outfalls and the Daliao River showed that nutrients of the Daliao River were affected by sewage outfalls. And the effect was significant and non-ignorable.


Assuntos
Rios/química , Poluentes Químicos da Água/análise , China , Nitrogênio/análise , Fósforo/análise , Esgotos/química , Qualidade da Água
17.
Huan Jing Ke Xue ; 35(9): 3336-45, 2014 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-25518649

RESUMO

The aim of this article was to explore the pollution level of heavy metals in the tidal reach and its adjacent sea estuary of Daliaohe area. The contents and spatial distribution of As, Cd, Cr, Cu, Ph and Zn in surface water, suspended solids and surface sediments were analyzed respectively. The integrated pollution index and geoaccumulation index were used to evaluate the contamination degree of heavy metals in surface water and surface sediments respectively. The results indicated that the contents of heavy metals in surface water was in the order of Pb < Cu < Cd < Cr < As < Zn. The heavy metal contents in surface water increased from river to sea. Compared with the contents of heavy metals in surface water of the typical domestic estuary in China, the overall contents of heavy metals in surface water were at a higher level. The contents of heavy metals in suspended solids was in the order of Cd < Cu < As < Cr

Assuntos
Monitoramento Ambiental , Estuários , Metais Pesados/análise , Poluentes Químicos da Água/análise , China , Sedimentos Geológicos/química , Rios/química , Análise Espacial , Qualidade da Água
18.
Sheng Li Ke Xue Jin Zhan ; 45(2): 118-20, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25069307
19.
Huan Jing Ke Xue ; 35(1): 108-16, 2014 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-24720193

RESUMO

The aim of this article is to explore the pollution level and contamination degree of heavy metals in the upper reaches of Hunhe River (Qingyuan Section). The contents and temporal-spatial distribution of Fe, Mn, Cu, Zn, Cd and As in surface water and surface sediments from the upper reaches of Hunhe River were analyzed respectively. The integrated pollution index and geoaccumulation index were used to evaluate the contamination degree of Cu, Zn, Cd and As. The results indicated that the contents of Mn, Cu, Zn, Cd and As in surface water from the upper reaches of Hunhe River during the wet season were higher than those during normal and dry season. Similar patterns of spatial distribution of Fe, Mn, Cu, Zn and Cd in surface water were observed, which showed that the highest content appeared at H7 station. The influence of pH, DO and hardness in the upper reaches of Hunhe River during the wet, normal and dry season on the distribution of heavy metal contents in surface water varied. Significant positive correlations were found among these elements in surface water, which implied that these elements probably had common pollution sources. The contents of Cu, Zn, Cd and Fe in surface sediments from the upper reaches of Hunhe River during the dry season were higher than those during the wet and normal season. Similar patterns of spatial distribution of Mn, Cu, Zn, As and Cd in surface sediments were also observed, which showed that the highest metal contents appeared in the midway of Hunhe River. The integrated pollution index assessment showed that the water quality in the upper reaches of Hunhe River was good except for individual stations, and that Cu, Cd and As were the main pollution elements in surface sediments in the upper reaches of Hunhe River.


Assuntos
Monitoramento Ambiental , Metais Pesados/análise , Rios/química , Poluentes Químicos da Água/análise , China , Sedimentos Geológicos/química , Medição de Risco , Análise Espaço-Temporal , Qualidade da Água
20.
Acta Pharmacol Sin ; 35(3): 351-5, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24487965

RESUMO

AIM: Thoracic aortic dissection (TAD) is the most common life-threatening disorder, and a shifted balance of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is involved in TAD pathogenesis. The aim of this study was to evaluate the association of 4 single-nucleotide polymorphisms (SNPs) in MMP-9 and TIMP-3 genes with TAD risk in Chinese Han population. METHODS: A total of 206 Chinese patients with TAD and 180 controls were included in this study. Four SNPs (rs3918249, rs2274756, rs9609643 and rs8136803) were genotyped using high-throughput MALDI-TOF mass spectrometry. Allele and genotype association analyses were conducted using PLINK. RESULTS: All the 4 SNPs resulted in Hardy-Weinberg equilibrium in patients and controls. The G allele frequency for the MMP-9 SNP rs2274756 was significantly higher in female TAD patients than in female controls (P=0.0099). Moreover, after adjusting for traditional cardiovascular risk factors (sex, age, hypertension, dyslipidemia, diabetes and smoking habit), the rs2274756 polymorphism (odds ratio: 0.30; 95% confidence interval: 0.11 to 0.79, P=0.015) resulted in an independent susceptibility factor for TAD in females. No associations were found between the other SNPs and TAD. CONCLUSION: The results provide strong evidence for an association between MMP-9 SNP rs2274756 and female TAD risk in Chinese Han population.


Assuntos
Aneurisma da Aorta Torácica/genética , Dissecção Aórtica/genética , Povo Asiático/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Inibidor Tecidual de Metaloproteinase-3/genética , Adolescente , Adulto , Idoso , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/enzimologia , Dissecção Aórtica/etnologia , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/enzimologia , Aneurisma da Aorta Torácica/etnologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco , Fatores Sexuais , Adulto Jovem
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