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1.
J Cell Mol Med ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32022386

RESUMO

Th22 cells are a novel subset of CD4+ T cells that primarily mediate biological effects through IL-22, with both Th22 cells and IL-22 being closely associated with multiple autoimmune and chronic inflammatory diseases. In this study, we investigated whether and how Th22 cells affect atherosclerosis. ApoE-/- mice and age-matched C57BL/6J mice were fed a Western diet for 0, 4, 8 or 12 weeks. The results of dynamic analyses showed that Th22 cells, which secrete the majority of IL-22 among the known CD4+ cells, play a major role in atherosclerosis. ApoE-/- mice fed a Western diet for 12 weeks and administered recombinant mouse IL-22 (rIL-22) developed substantially larger plaques in both the aorta and aortic root and higher levels of CD3+ T cells, CD68+ macrophages, collagen, IL-6, Th17 cells, dendritic cells (DCs) and pSTAT3 but lower smooth muscle cell (SMC) α-actin expression than the control mice. Treatment with a neutralizing anti-IL-22 monoclonal antibody (IL-22 mAb) reversed the above effects. Bone marrow-derived DCs exhibited increased differentiation into mature DCs following rIL-22 and ox-LDL stimulation. IL-17 and pSTAT3 were up-regulated after stimulation with IL-22 and ox-LDL in cells cocultured with CD4+ T cells and mature DC supernatant, but this up-regulation was significantly inhibited by IL-6mAb or the cell-permeable STAT3 inhibitor S31-201. Thus, Th22 cell-derived IL-22 aggravates atherosclerosis development through a mechanism that is associated with IL-6/STAT3 activation, DC-induced Th17 cell proliferation and IL-22-stimulated SMC dedifferentiation into a synthetic phenotype.

2.
Aging (Albany NY) ; 12(1): 193-203, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31901899

RESUMO

Our previous studies have demonstrated that interleukin-12p35 knockout (IL-12p35 KO) regulates the progression of various cardiovascular diseases, such as acute cardiac injury and hypertension. The aims of this study were to investigate whether IL-12p35 KO affects aging-related cardiac remodeling and to explore the possible mechanisms. First, the effects of IL-12p35 KO on heart structure and function were detected, and the results showed that IL-12p35 KO exacerbated cardiac remodeling and increased cardiac senescence-related protein levels in aged mice. In addition, whether IL-12p35 KO regulates cardiac senescence-related protein expression, cardiac mitochondrial dysfunction and cardiomyocyte apoptosis was also investigated. IL-12p35 KO increased mitochondrial calcium fluorescence intensity and ROS fluorescence intensity, while it reduced mitochondrial membrane potential. Furthermore, reduced mitochondrial complex (I-IV) activity and ATP levels and increased apoptosis-inducing factor (AIF)-related cardiomyocyte apoptosis were observed in aged IL-12p35 KO mice compared with wild-type mice. Our results demonstrate that aging is aggravated by IL-12p35 KO and that the mechanism may be related to exacerbation of mitochondrial dysfunction and AIF-related cardiomyocyte apoptosis.

3.
Medicine (Baltimore) ; 98(50): e18241, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852089

RESUMO

T helper 17 (Th17) cells are related to the progression of aortic dissection. This study aimed to determine whether circulating Th17 levels are associated with the prognosis of acute Stanford type B aortic dissection (STBAD) after thoracic endovascular aortic repair (TEVAR).A cohort study was performed and STBAD patients (n = 140) received TEVAR were enrolled, the circulating Th17 levels were measured and the patients were divided into low and high Th17 groups, and 36 months of follow-up was performed. The data for mortality, survival outcomes, heart structure and function changes, aortic regurgitation prevalence, and aortic remodeling outcomes were recorded.Lower mortality and fewer complications were observed in the low Th17 group than in the high Th17 group in the third year of follow-up. In addition, the low Th17 group exhibited better cardiac remodeling and cardiac function when compared with that in the high Th17 group in the second to third year after TEVAR. Aortic reflux was improved in both groups but was more pronounced in the low Th17 group. During follow-up, the true lumen of the proximal thoracic aorta at the level of the celiac trunk in both the low and high Th17 groups continuously enlarged and was more pronounced in the low Th17 group.Circulating Th17 cells were related to cardiac and aortic remodeling and prognosis during STBAD after TEVAR. Anti-inflammatory therapy may be useful for STBAD patients who have undergone TEVAR.


Assuntos
Aneurisma Dissecante/sangue , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/sangue , Procedimentos Endovasculares/métodos , Células Th17/patologia , Remodelação Vascular , Doença Aguda , Adulto , Aneurisma Dissecante/diagnóstico , Aneurisma Dissecante/cirurgia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiopatologia , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/cirurgia , Angiografia por Tomografia Computadorizada , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Tempo
4.
Clin Chim Acta ; 497: 104-109, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31326419

RESUMO

BACKGROUND: Interleukin-32 (IL-32) is a cytokine associated with higher risk of cardiovascular diseases in inflammatory environments. This study aimed to investigate the IL-32 levels in coronary artery disease (CAD) patients. METHODS: IL-32 expression in coronary arteries from both normal donors and CAD patients were analyzed. Plasma IL-32, IFN-γ and IL-17 levels in stable angina pectoris (SAP, n = 80) patients, unstable angina pectoris (UAP, n = 96) patients, acute myocardial infarction (AMI, n = 72) patients and patients exhibiting chest pain unrelated to coronary artery disease (NCAD, n = 72) were measured. Additionally, whether plasma IL-32 levels were independent correlated with the presence of CAD was analyzed. RESULTS: IL-32 was high expressed in atherosclerotic plaques of CAD patients when compared with normal coronary arteries, and macrophages were the major sources of IL-32. Compared with the NCAD group, IL-32, IFN-γ and IL-17 levels were increased in the CAD group and gradually increased through the SAP, UAP and AMI groups. Plasma IL-32 levels were positively correlated with the Gensini score, IFN-γ levels and IL-17 levels in CAD patients. The results of linear regression showed that IL-32 was independently associated with the occurrence of CAD. CONCLUSION: Both the coronary artery and circulating IL-32 levels were increased in CAD patients and IL-32 may be a marker of noninvasive diagnosis of CAD.

5.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(10): 1338-1349, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31125703

RESUMO

Mature dendritic cells (DCs) play a pathogenic role in atherosclerosis. Our previous study demonstrated that exogenous interleukin (IL)-37 suppresses the maturation of DCs, induces the T-regulatory (Treg) cell response, and attenuates atherosclerosis in ApoE-/- mice. The aim of the present study was to explore the molecular mechanism of IL-37 on the maturation of DCs throughout the development of atherosclerosis. The expression of interleukin-1 receptor 8 (IL-1R8), which is a single Ig-domain receptor that was recently found to be pivotal for the extracellular function of IL-37, Toll-like receptor (TLR) 4 and p65, was measured in ApoE-/- mice and IL-37 transgenic (IL-37tg) ApoE-/- mice. IL-1R8 was mainly expressed in aortic plaque-infiltrated DCs and at significantly higher levels in IL-37tg atherosclerotic mice, accompanied by lower levels of TLR4 and p65. Furthermore, IL-37 eliminated the maturation of DCs induced by oxidized low-density lipoprotein (oxLDL) and caused marked upregulation of IL-1R8 in vitro and downregulation of TLR4 and p65, which was consistent with the experiments in mice. However, the inhibitory effect of IL-37 on the maturation of DCs in vitro was abolished when IL-37 was used to treat DCs isolated from IL-1R8-deficient and TLR4-deficient mice. Therefore, this study indicated that IL-37 inhibited the maturation of DCs via the IL-1R8-TLR4-NF-κB pathway and attenuated atherosclerosis in ApoE-/- mice.

6.
Life Sci ; 230: 104-110, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31128138

RESUMO

BACKGROUND: Previous studies have demonstrated that type 2 diabetes mellitus (T2DM) is negatively correlated with the occurrence of aortic dissection (AD). This study aimed to investigate the effects of T2DM on the prognosis of Stanford type B AD (STBAD) patients after thoracic endovascular aortic repair (TEVAR). METHODS: STBAD patients (n = 141) who underwent TEVAR received an oral glucose tolerance test (OGTT) and were divided into a normal glucose (NG, n = 55) group, an abnormal glucose tolerance (AGT, n = 48) group and a T2DM (n = 38) group according to the results of the OGTT. Data on mortality, clinical complications, left ventricular (LV) remodeling and aortic remodeling were collected during the 3-year follow-up. RESULTS: Lower mortality and fewer clinical complications after TEVAR were found in the T2DM group than in the NG group. Multivariate linear regression analysis showed that 2-hour postprandial glucose (Glu-2h) was negatively correlated with mortality and the occurrence of clinical complications in STBAD patients after TEVAR. In addition, better LV remodeling, larger true lumen areas and smaller false lumen areas in both the proximal aortas and abdominal aortas were observed in the T2DM group than in the NG group. Furthermore, no significant differences in mortality or clinical complications after TEVAR were found between the NG group and the AGT group or between the T2DM group and the AGT group. CONCLUSION: During the 3-year follow-up period, mortality and clinical complications in STBAD patients after TEVAR were significantly reduced in the T2DM group. For STBAD patients who undergo TEVAR, properly relaxing of blood glucose control requirements may be beneficial for their prognosis.


Assuntos
Aneurisma Dissecante/fisiopatologia , Aorta Torácica/cirurgia , Adulto , Idoso , Aneurisma Dissecante/mortalidade , Aneurisma Dissecante/cirurgia , Aorta Abdominal/fisiopatologia , Aorta Torácica/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Seguimentos , Glucose/metabolismo , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Remodelação Vascular
7.
Mediators Inflamm ; 2019: 3152040, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31093011

RESUMO

Interleukin- (IL-) 35, a novel functional cytokine of regulatory T cells (Treg) comprised of the IL-12p35 subunit and the other subunit Epstein-Barr virus-induced gene 3 (EBI3), regulates the activity of CD4+ T cells and macrophages, thereby playing a critical role in inflammatory and autoimmune diseases. Previous studies demonstrated that both recombinant mice and human IL-35 attenuated atherosclerosis in ApoE-/- mice. Additionally, EBI3 deficiency enhanced the activation of macrophages and increased atherosclerotic lesions in LDLR-/- mice. This study generated double-deficient mice for ApoE and IL-12p35 (ApoE-/- IL-12p35-/- mice) and investigated the effect of IL-12p35 deficiency on atherosclerosis. IL-12p35 deficiency alleviated Th1/Th2 imbalance, aggravated Th17/Treg imbalance, and attenuated atherosclerotic plaque formation in ApoE-/- mice. Additionally, exogenous rIL-35 treatment reversed the imbalance of Th17/Treg and attenuated atherosclerosis in ApoE-/- mice. These findings suggest that IL-12p35 deficiency ameliorates atherosclerosis in ApoE-/- mice, partially, via attenuating the Th1/Th2 imbalance, although IL-12p35 deficiency aggravates the Th17/Treg imbalance.


Assuntos
Subunidade p35 da Interleucina-12/metabolismo , Células Th1/metabolismo , Células Th2/metabolismo , Animais , Apolipoproteínas E , Aterosclerose/imunologia , Aterosclerose/metabolismo , Imuno-Histoquímica , Interleucina-10/metabolismo , Subunidade p35 da Interleucina-12/deficiência , Interleucina-4/metabolismo , Masculino , Camundongos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo
8.
Mediators Inflamm ; 2019: 1575410, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30728748

RESUMO

Background: Interleukin-11 (IL-11) is an important inflammatory cytokine and has been demonstrated to participate in cardiovascular diseases. However, there have been no studies about the role of IL-11 in heart failure (HF). The present study is aimed at investigating whether IL-11 levels are associated with the cardiac prognosis in patients with HF. Methods: The plasma concentrations of IL-11 were measured in 240 patients with chronic HF (CHF) and 80 control subjects without signs of significant heart disease. In addition, we prospectively followed these CHF patients to endpoints of cardiac events. Results: Compared with the control group, the plasma IL-11 concentrations were significantly increased in the CHF patients and gradually increased in the New York Heart Association (NYHA) functional class II group, the NYHA functional class III group, and the NYHA functional class IV group. The receiver operating characteristic (ROC) curve revealed that the predictive role of IL-11 in HF is not as good as N-terminal B-type natriuretic peptide (BNP), although IL-11 has a certain value in predicting cardiac events. In addition, the CHF patients were divided into 3 groups according to the plasma IL-11 concentration category (low, T1; middle, T2; and high, T3). The multivariate Cox hazard analysis showed that the high plasma IL-11 concentrations were independently associated with the presence of cardiac events after adjustment for confounding factors. Furthermore, the CHF patients were divided into two groups based on the median plasma IL-11 concentrations. The Kaplan-Meier analysis revealed that the patients with high IL-11 concentrations had a higher risk of cardiac events compared with those with low IL-11 concentrations. Conclusions: Higher plasma IL-11 levels significantly increase the presence of cardiac events and suggest a poor outcome; although the diagnostic value of IL-11 in CHF is not as good as BNP, there is a certain value in predicting cardiac events in CHF.


Assuntos
Insuficiência Cardíaca/sangue , Interleucina-11/sangue , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Estudos de Casos e Controles , Doença Crônica , Citocinas/metabolismo , Ecocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca/complicações , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Alta do Paciente , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Curva ROC , Função Ventricular Esquerda
9.
Can J Cardiol ; 35(1): 42-50, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30595182

RESUMO

BACKGROUND: Previous studies have shown that thrombospondin 1 (TSP-1) is involved in cardiovascular diseases, such as atherosclerosis and abdominal aortic aneurysm. However, TSP-1 expression levels in human aortic dissection (AD) remain unknown. METHODS: TSP-1 levels were detected in aortas collected from control subjects and AD patients. The TSP-1, interleukin (IL) 6, matrix metalloproteinase (MMP) 2, and MMP9 levels in plasma from non-AD patients and AD patients were measured. In addition, the effects of recombinant mouse TSP-1 protein on macrophage differentiation and smooth muscle cell (SMC) apoptosis were investigated. RESULTS: Compared with the aortas from control subjects, aortas from AD patients showed a significant increase in TSP-1 expression, especially in the torn sections. SMCs and endothelial cells produced TSP-1, but SMCs were the main source. TSP-1, IL-6, MMP2, and MMP9 levels were higher in AD patients than in non-AD patients, and plasma IL-6, MMP2, and MMP9 levels were positively correlated with TSP-1 levels in AD patients. Simple linear regression analysis and multivariate linear regression analysis showed that TSP-1 levels were independently correlated with the onset of AD. In cultured cells, recombinant mouse TSP-1 further increased inducible nitric oxide synthase (iNOS) mRNA expression in angiotensin (Ang) II-treated macrophages, whereas it reduced B-cell lymphoma-2 (Bcl2) mRNA levels and increased Bcl2-associated X protein (Bax) mRNA levels in Ang II-treated SMCs. CONCLUSIONS: TSP-1 level is significantly increased in AD patients and might participate in AD via promoting classically activated macrophage (M1) macrophage differentiation and SMC apoptosis.


Assuntos
Aneurisma Dissecante/genética , Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/genética , Regulação da Expressão Gênica , Músculo Liso Vascular/metabolismo , RNA/genética , Trombospondina 1/genética , Doença Aguda , Adulto , Aneurisma Dissecante/metabolismo , Aneurisma Dissecante/patologia , Animais , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/patologia , Western Blotting , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Músculo Liso Vascular/patologia , Reação em Cadeia da Polimerase , Trombospondina 1/biossíntese
10.
Cardiovasc Res ; 115(6): 1102-1113, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30395167

RESUMO

AIMS: Numerous studies have demonstrated that inflammation is involved in the progression of hypertension. Inflammatory cytokines interleukin (IL)-12 and IL-35 belong to the IL-12 cytokine family and share the same IL-12p35 subunit. Accumulating evidence has demonstrated that IL-12p35 knockout (IL-12p35 KO) leads to cardiovascular disease by regulating the inflammatory response. This study aimed to investigate whether IL-12p35 KO elevates blood pressure in a hypertension mouse model. METHODS AND RESULTS: Mice with angiotensin (Ang) II infusion showed marked aortic IL-12p35 expression; thus, aortic macrophages may be the main source of IL-12p35. Wild-type and IL-12p35 KO mice were infused with Ang II or saline. IL-12p35 KO promoted M1 macrophage differentiation, amplified the inflammatory response, aggravated vascular dysfunction, and elevated blood pressure in Ang II-treated mice. Then, some Ang II-infused mice were given phosphate buffer saline, mouse recombinant IL-12 (rIL-12), or rIL-35, and the results showed that rIL-12 but not rIL-35 treatment had an antihypertensive effect on Ang II-infused mice. In addition, detection of human plasma IL-12 levels in hypertensive patients and control subjects showed that IL-12 was significantly increased in hypertensive patients when compared with control subjects. In hypertensive patients, IL-12 levels were positively correlated with blood pressure. CONCLUSION: IL-12p35 KO amplifies the inflammatory response and promotes blood pressure elevation in Ang II-treated mice. In addition, IL-12, but not IL-35, plays a protective role in the Ang II-induced hypertension model. Thus, IL-12 may be a novel therapeutic agent for the prevention and treatment of clinical hypertension.

11.
Life Sci ; 218: 132-138, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30594664

RESUMO

BACKGROUND: Previous studies have demonstrated that oxidative stress is closely related to aortic dissection (AD). Sestrin2 (Sesn2) is an important antioxidant protein, and this study aimed to investigate whether Sesn2 participates in AD and the possible mechanisms. METHODS: Sesn2 expression was detected in aortas collected from AD patients and normal donors. In addition, blood samples were collected from AD patients and non-AD (NAD) patients, and the plasma Sesn2 levels were measured. Furthermore, the effects of Sesn2 on angiotensin (Ang) II-induced smooth muscle cell (SMC) apoptosis were investigated in vitro. RESULTS: Compared with the aortas from normal donors, aortas from AD patients had significantly increased Sesn2. Sesn2 was mainly secreted by macrophages, and low levels were secreted by CD4+ T lymphocytes, but not SMCs. Plasma Sesn2 levels were also increased in AD patients compared with NAD patients. Sesn2 levels were negatively corrected with superoxide dismutase (SOD) levels but positively corrected with malondialdehyde (MDA) levels in AD patients. In co-cultures of macrophages and SMCs, Sesn2 overexpression in macrophages significantly reduced Ang II-induced SMC apoptosis, and this effect could be reversed by Nrf2 silencing. CONCLUSIONS: Sesn2 is increased in both aortas and plasma from AD patients. Sesn2 may alleviate Ang II-induced SMC apoptosis and participate in AD via the Nrf2 pathway. Sesn2 may be a new target in the treatment and prevention of AD.


Assuntos
Angiotensina II/farmacologia , Aorta/patologia , Doenças da Aorta/patologia , Apoptose , Miócitos de Músculo Liso/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Nucleares/metabolismo , Aneurisma Dissecante , Aorta/efeitos dos fármacos , Aorta/metabolismo , Doenças da Aorta/metabolismo , Doenças da Aorta/cirurgia , Biomarcadores/metabolismo , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Feminino , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Fator 2 Relacionado a NF-E2/genética , Proteínas Nucleares/genética , Estresse Oxidativo , Vasoconstritores/farmacologia
12.
EBioMedicine ; 35: 29-39, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30228093

RESUMO

BACKGROUND: Recent evidence has demonstrated that interleukin 12p35 knockout (IL-12p35 KO) is involved in cardiac diseases by regulating the inflammatory response. The involvement of inflammatory cells has also been observed in doxorubicin (DOX)-induced cardiac injury. This study aimed to investigate whether IL-12p35 KO affects DOX-induced cardiac injury and the underlying mechanisms. METHODS: First, the effect of DOX treatment on cardiac IL-12p35 expression was assessed. In addition, to investigate the effect of IL-12p35 KO on DOX-induced cardiac injury, IL-12p35 KO mice were treated with DOX. Because IL-12p35 is the mutual subunit of IL-12 and IL-35, to determine the cytokine that mediates the effect of IL-12p35 KO on DOX-induced cardiac injury, mice were given phosphate-buffered saline (PBS), mouse recombinant IL-12 (rIL-12) or rIL-35 before treatment with DOX. RESULTS: DOX treatment significantly increased the level of cardiac IL-12p35 expression. In addition, IL-12p35 KO mice exhibited higher serum and heart lactate dehydrogenase levels, higher serum and heart creatine kinase myocardial bound levels, and greater cardiac dysfunction than DOX-treated mice. Furthermore, IL-12p35 KO further increased M1 macrophage and decreased M2 macrophage differentiation, aggravated the imbalance of oxidants and antioxidants, and further activated the mitochondrial apoptotic pathway and endoplasmic reticulum stress autophagy pathway. Both rIL-12 and rIL-35 protected against DOX-induced cardiac injury by alleviating the inflammatory response, oxidative stress, apoptosis and autophagy. CONCLUSIONS: IL-12p35 KO aggravated DOX-induced cardiac injury by amplifying the levels of inflammation, oxidative stress, apoptosis and autophagy. (234 words).


Assuntos
Apoptose , Autofagia , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/fisiopatologia , Doxorrubicina/efeitos adversos , Inflamação/patologia , Subunidade p35 da Interleucina-12/deficiência , Estresse Oxidativo , Animais , Apoptose/efeitos dos fármacos , Autofagossomos/metabolismo , Autofagossomos/ultraestrutura , Autofagia/efeitos dos fármacos , Biomarcadores/metabolismo , Cardiotônicos/metabolismo , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Subunidade p35 da Interleucina-12/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/patologia , Miocárdio/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo
13.
Mediators Inflamm ; 2018: 5697149, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30258282

RESUMO

Background: Previous studies demonstrated that the subsets of CD4+ T helper (Th) cells are closely related to vascular diseases, including atherosclerosis and hypertension. This study is aimed at investigating the circulating Th1, Th2, Th9, Th17, Th22, and Treg levels in aortic dissection (AD) patients. Methods: Blood samples from AD (n = 56) and non-AD (NAD, n = 24) patients were collected, and the circulating levels of Th1, Th2, Th9, Th17, Th22, and Treg cells and their transcription factors and functional cytokines were measured by flow cytometric analysis, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assays, respectively. In addition, the human aortic vascular smooth muscle cells (HASMCs) were treated with saline, angiotensin II (Ang II), or plasma from AD patients. Results: Compared with the levels in the NAD group, the Th1, Th9, Th17, Th22, and their transcription factor levels were increased and the Th2, Treg, and their transcription factor levels exhibited a decreasing trend in AD patients. In addition, higher IFN-γ, IL-9, IL-17, and IL-22 levels and lower IL-4 and IL-35 levels were observed in AD patients. Simple linear regression analysis and binary logistic regression analysis suggested that Th1/IFN-γ, IL-9, Th17/IL-17, and Th22/IL-22 positively regulated the occurrence of AD, while Th2/IL-4 and Treg/IL-35 negatively regulated the occurrence of AD. Plasma from AD patients further increased Bax mRNA levels but decreased Bcl2 and α-SMA mRNA levels in Ang II-treated HASMCs. Conclusions: Changes in Th1, Th2, Th9, Th17, Th22, and Treg activity are associated with the onset of AD. Different subsets of CD4+ T cells play different roles in the presence of AD.


Assuntos
Aneurisma Dissecante/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th1/metabolismo , Células Th17/metabolismo , Células Th2/metabolismo , Apoptose/fisiologia , Linfócitos T CD4-Positivos/metabolismo , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Interleucina-17/metabolismo , Interleucina-4/metabolismo , Interleucina-9/metabolismo , Interleucinas/metabolismo , Masculino , Pessoa de Meia-Idade
14.
Iran J Public Health ; 47(7): 1017-1029, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30182001

RESUMO

Background: We aimed to find a potential earlier diagnostic strategy for acute myocardial infarction (AMI) by investigating the epidemiology and serum metabolic characteristics of AMI patients in comparison with those of chest pain controls (CPCS). Methods: We conducted this prospective, non-randomized, observational study of patients with acute chest pain symptoms presenting to the Emergency Rooms (ER) in The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Province, China from January 2015 to July 2016. We included a cohort of 45 patients with AMI together with 45 age- and sex-matched CPCS. The epidemiology of AMI was collected, and the phenotypic characteristics of the serum metabolite composition of AMI patients were determined using a combination of 1H nuclear magnetic resonance (NMR)-based metabolomics and clinical assays. Results: The epidemiology showed that elderly AMI patients with chest pain syndrome presenting to ER have little awareness of their physical condition and compliance with medication. Significant serum metabolic differences observed between AMI patients and CPCS were highlighted by system differentiations in multiple metabolic pathways including anaerobic glycolysis, gluconeogenesis, tricarboxylic acid cycle (TCA cycle), protein biosynthesis, lipoprotein changes, choline and fatty acid metabolisms and intestinal microbial metabolism. Conclusion: The epidemiology and serum metabolic phenotypes observed here demonstrated that integration of metabolomics with other techniques could be useful for better understanding the biochemistry of AMI and for potential AMI molecular diagnosis. We should improve the general public's awareness of AMI, including early symptoms, risk factors, emergency responses, and treatments for related comorbidities.

17.
Clin Chim Acta ; 486: 177-182, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30086263

RESUMO

Aortic dissection (AD) is one of the most dangerous forms of vascular disease, characterized by endometrial rupture and intramural hematoma formation. Generally, the pathological process is complicated and closely related to the infiltration of inflammatory cells into the aortic wall and apoptosis of vascular smooth muscle cells. Currently, multiple cytokines, including interleukins, interferon, the tumor necrosis factor superfamily, colony stimulating factor, chemotactic factor, growth factor and so on, have all been demonstrated to play a critical role in AD. Additionally, studies of the link between cytokines and AD could deepen our understanding of the disease and may guide future treatment therapies; therefore, this review focuses on the role of cytokines in AD.


Assuntos
Aneurisma Dissecante/metabolismo , Citocinas/metabolismo , Aneurisma Dissecante/tratamento farmacológico , Aneurisma Dissecante/patologia , Animais , Apoptose , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia
18.
Clin Chim Acta ; 486: 381-386, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30144436

RESUMO

BACKGROUND: Previous studies demonstrated that the transforming growth factor (TGF) ß superfamily, including TGF-ßs and bone morphogenetic proteins (BMPs), plays important roles in cardiovascular diseases. The kielin/chordin-like protein (KCP) is a secreted protein that regulates the expression and function of TGF-ßs and BMPs. However, the role of KCP during heart failure (HF) remains unknown. The present study aimed to investigate the cardiac expression of KCP in human failing hearts. METHODS: The human failing heart samples from patients with dilated cardiomyopathy (DCM, n = 12) and ischemic cardiomyopathy (ICM, n = 12) were collected, and normal heart (n = 8) samples from unmatched donors were collected as controls. Collagen volume, KCP levels, and mRNA levels of several BMPs in left ventricles (LV) of all hearts were measured. RESULTS: The KCP levels were significantly higher in human failing hearts than in normal hearts. KCP levels were positively associated with hypertrophy markers, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and ß-myosin heavy chain (ß-MHC). In addition, KCP levels were also positively associated with left ventricular end-diastolic dimension (LVEDD), collagen Iα and collagen IIIα expression but were negatively associated with left ventricular ejection fraction (LVEF). Furthermore, increased TGF-ß1, BMP2/4/6/10 and reduced BMP7 levels were observed, and positive correlations between KCP and TGF-ß1 and negative correlation between KCP and BMP2/7 were found, but not for BMP4/6/10. CONCLUSIONS: KCP was closely associated with heart failure. The regulation of BMP2/7 and TGF-ß1 expression may be the possible mechanisms.


Assuntos
Proteínas de Transporte/metabolismo , Insuficiência Cardíaca/metabolismo , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Feminino , Insuficiência Cardíaca/patologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
19.
Coron Artery Dis ; 29(5): 423-428, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29738342

RESUMO

OBJECTIVES: Inflammatory cytokines play an important role in the pathogenesis of cardiovascular disease. Few studies have investigated the association between interleukin-35 (IL-35) genetic variants and the risk of coronary heart disease (CHD). We examined the association between IL-35 polymorphisms and CHD in the Chinese Zhuang population. PATIENTS AND METHODS: A total of 707 CHD patients and 707 age-matched and sex-matched controls were enrolled in this case-control study. Genotypes of the single nucleotide polymorphisms (SNPs) of IL-35, including rs428253, rs6613, rs9807813, rs2243115, rs568408, rs582054, rs583911, rs4740, and rs393581, were examined by MassArray. Plasma IL-35 level was measured using an enzyme-linked immunosorbent assay. The multivariate logistic regression model was used to evaluate the association between the SNPs and the risk of CHD. RESULTS: In the Chinese Zhuang population, compared with the GG genotype of EBI3 rs428253, individuals with the CC genotype had a 2.02-fold (95% confidence interval: 1.07-3.84, P=0.031) higher risk of CHD. Further adjustment for potential risk factors did not alter the positive association (CC vs. GG, odds ratio=2.30, 95% confidence interval: 1.16-4.54, P=0.042). SNPs rs4740, rs2243115, rs568408, and rs582054 were not statistically related to the risk of CHD. The plasma IL-35 levels showed a marginally significant difference between rs428253 genotypes [GG: 13.39 (7.89-19.25) vs. CC+GC: 17.53 (8.98-22.56) pg/ml, P=0.057]. CONCLUSION: The EBI3 rs428253 CC genotype was associated with an increased risk of CHD in the Chinese Zhuang population, although no significant difference in IL-35 levels was observed between genotypes in healthy controls.


Assuntos
Doença das Coronárias/genética , Subunidade p35 da Interleucina-12/genética , Interleucinas/genética , Antígenos de Histocompatibilidade Menor/genética , Polimorfismo de Nucleotídeo Único , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Doença das Coronárias/sangue , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/etnologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Heterozigoto , Homozigoto , Humanos , Subunidade p35 da Interleucina-12/sangue , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor/sangue , Fenótipo , Fatores de Risco
20.
Clin Chim Acta ; 481: 193-199, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29555322

RESUMO

BACKGROUND: Interleukin (IL) 11 is closely related to tumor and hematological system diseases. Recent studies have demonstrated that IL-11 also participates in cardiovascular diseases, including ischemia-reperfusion mediated heart injury and acute myocardial infarction. This study aimed to investigate whether IL-11 is involved in acute thoracic aortic dissection (TAD). METHODS: Aortic tissue samples from normal donors and acute TAD patients were collected, and the expression of IL-11 in all aortic tissue was analyzed. In addition, blood samples from patients with chest pain were collected and divided into a non-AD (NAD) group and a TAD group according to the results of computed tomography angiography of the thoracic aorta. The plasma IL-11, IL-17 and interferon (IFN) γ in all blood samples were measured. RESULTS: Compared with aortic tissue of normal controls, IL-11 was significantly increased in aortic tissue of acute TAD patients, especially in the torn section. The IL-11 was derived from aorta macrophages in TAD. In addition, the plasma IL-11, IL-17 and IFN-γ were significantly higher in acute TAD patients than in NAD patients, and the correlation analysis showed that IL-11 levels were positively correlated with levels of IFN-γ, IL-17, glucose, systolic blood pressure, diastolic blood pressure, white blood cells, C-reactive proteins and D-dimers. Binary logistic regression analyses showed that elevated IL11 in patients who may have diagnostic value of TAD, but less that D-dimer. CONCLUSION: IL-11 was increased in thoracic aorta and plasma of TAD patients and may be a promising biomarker for diagnosis in patients with TAD.


Assuntos
Aneurisma Dissecante/sangue , Aneurisma Dissecante/diagnóstico , Aorta Torácica/química , Aneurisma da Aorta Torácica/sangue , Interleucina-11/sangue , Adulto , Idoso , Aneurisma da Aorta Torácica/diagnóstico , Feminino , Humanos , Interleucina-11/biossíntese , Masculino , Pessoa de Meia-Idade , Análise de Regressão
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