RESUMO
Cellular senescence is an irreversible arrest of cell proliferation triggered by different stimuli, including DNA damage, telomere shortening and oncogenic stress. Senescent cells, by releasing the senescence-associated-secretory-phenotype (SASP), contribute to various diseases pathogenesis. Human atherosclerotic plaque contains cells with multiple markers of senescence that associate with disease severity. We characterized the frequency of senescent cTfh cells and genes expressions before and after treatment with Dasatinib in patients with different degrees of stenosis. Twelve high (≥50%), and twelve low (<50%) stenosis patients and six healthy controls were enrolled. The percentage of senescent CD3+CD4+CXCR5+CD153+CD57+ cells was significantly decreased in Dasatinib treated cells from individuals with low and high stenosis (P = 0.0007 and P = 0.0002, respectively). However, the frequency of total lymphocytes, CD3+ and CD4+ T cells were not significantly different between the groups before and after treatment. The expression levels of P53 (P = 0.0003 and P = 0.0001), P16 (P = 0.0005 and P = 0.0002), p21 (P = 0.0002 and P < 0.0001), SENEX (P = 0.0005 and P < 0.0001) and BCL-2 (P = 0.0005 and P = 0.0002) were decreased in PBMCs of low and high stenosis groups after treatment with Dasatinib, respectively. The percentage of senescent cTfh cells positively correlated with cholesterol (P = 0.034; r = 0.671), C-reactive protein (CRP) (P = 0.029; r = 0.707), Erythrocyte sedimentation rate (ESR) levels (P = 0.030; r = 0.598) and neutrophil counts (P = 0.021; r = 0.799) in patients with high stenosis. The decreased frequency of senescent cTfh cells and the expression levels of senescence genes after Dasatinib treatment in patients with atherosclerosis suggest a role for Dasatinib in partial clearance or rejuvenation of senescent cTfh cells, which may decrease inflammatory mediators and attenuate disease progression.
Assuntos
Aterosclerose/imunologia , Senescência Celular/efeitos dos fármacos , Estenose Coronária/imunologia , Dasatinibe/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Células T Auxiliares Foliculares/efeitos dos fármacos , Aterosclerose/genética , Células Cultivadas , Senescência Celular/genética , Estenose Coronária/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Células T Auxiliares Foliculares/imunologiaRESUMO
BACKGROUND: Diabetes increases the risk of myocardial infarction (MI) by 2 to 3 folds. Tlymphocytes play a role in atherosclerosis, which is the main pathology behind MI. Cellular immune responses to beta-2 glycoprotein I (ß2GPI) are shown in carotid atherosclerosis. OBJECTIVE: To investigate the self-reactive, ß2GPI-specific T-lymphocytes in patients with and without diabetes and atherosclerosis. METHODS: Collectively, 164 subjects with and without diabetes that underwent coronary angiography were divided into four groups based on their diabetes status and coronary stenosis. Group I=Diabetic with ≥50% stenosis: A+D+ (n=66); Group II=Non-diabetic with ≥50% stenosis, A+D- (n=39); Group III=Diabetic with <50% stenosis: A-D+ (n=28); and Group IV=Non-diabetic with <50% stenosis: AD- (n=31). All groups were evaluated for anti-ß2GPI IgG antibody by ELISA method. Then, PBMCs were isolated from 18 subjects and were stimulated with ß2GPI-derived peptides to assess their proliferation in accordance with their HLA-DRB1 alleles. RESULTS: Mean ß2GPI IgG levels were higher in groups with ≥50% stenosis (A+) compared to those with <50% stenosis (A-), (P=0.02). The co-presence of diabetes in A+ individuals increased mean ß2GPI-specific IgG. Auto-reactive ß2GPI-specific T cells were detected in the repertoire of T-lymphocytes in all groups. ß2GPI-peptides showed promiscuous restriction by various HLADRB1. CONCLUSION: ß2GPI is the target of cellular and humoral immune responses in patients with atherosclerosis. Since the T cell responses but not antibodies were detectable in A-D+ and A-D- groups, it is reasonable to assume that cellular responses preceded the humoral responses. Post-translation modifications of ß2GPI under oxidative and glycemic stresses may have increased the IgG levels in patients with diabetes. Finally, identification of antigens that trigger immuno-pathogenesis in atherosclerosis and diabetes may help the development of immunomodulation methods to prevent or treat these debilitating diseases.
Assuntos
Anticorpos Anticardiolipina/sangue , Linfócitos T CD4-Positivos/imunologia , Proliferação de Células , Estenose Coronária/imunologia , Diabetes Mellitus/imunologia , Ativação Linfocitária , beta 2-Glicoproteína I/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD4-Positivos/metabolismo , Células Cultivadas , Angiografia Coronária , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/metabolismo , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/metabolismo , Epitopos , Feminino , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologia , Humanos , Imunidade Celular , Imunidade Humoral , Masculino , Pessoa de Meia-IdadeRESUMO
Aim: The study aimed to investigate and compare the predictive capacity of a systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to determine a hemodynamically significant coronary artery stenosis assessed by fractional flow reserve (FFR). Patients & methods: A total of 207 chronic coronary syndrome patients with FFR measurement were enrolled in the study. NLR, PLR and SII levels were calculated. Results: The cut-off value of the SII (620) was associated with 78.4% sensitivity and 64.0% specificity to predict a hemodynamically significant stenosis. SII level independently predicted FFR ≤0.80. Conclusion: SII is an independent predictor of functionally significant coronary stenosis detected by FFR in chronic coronary syndrome patients. SII levels can predict hemodynamically severe obstruction better than NLR and PLR.
Assuntos
Estenose Coronária/diagnóstico , Estenose Coronária/imunologia , Reserva Fracionada de Fluxo Miocárdico/imunologia , Idoso , Biomarcadores , Plaquetas , Angiografia Coronária , Estenose Coronária/metabolismo , Técnicas de Diagnóstico Cardiovascular , Feminino , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Humanos , Inflamação , Contagem de Linfócitos , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Prognóstico , Estudos RetrospectivosRESUMO
AIMS: Immune endothelial inflammation, underlying coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features. METHODS: Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score = 0, uninjured coronaries and with no obstructive CHD (no critical stenosis, NCS) were considered as control subjects (n = 18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software. RESULTS: For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p = 0.05) of HLA-G gene in CHD patients compared to control group; 2) the hypomethylation level of one specific fragment of 161bp (+616/+777) positively correlated with coronary Ca score, a relevant parameter of CCTA (p<0.05) between two groups evaluated and was predictive for disease severity. CONCLUSIONS: Reduced levels of circulating HLA-G molecules could derive from epigenetic marks. Epigenetics phenomena induce hypomethylation of specific regions into 5'UTR-CpG island of HLA-G gene in CHD patients with obstructive non critical stenosis vs coronary stenosis individuals.
Assuntos
Doença das Coronárias/genética , Doença das Coronárias/imunologia , Metilação de DNA , Antígenos HLA-G/genética , Regiões 5' não Traduzidas , Adulto , Idoso , Cálcio/metabolismo , Estudos de Casos e Controles , Angiografia por Tomografia Computadorizada , Doença das Coronárias/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/genética , Estenose Coronária/imunologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/imunologia , Vasos Coronários/metabolismo , Ilhas de CpG , Epigênese Genética , Feminino , Antígenos HLA-G/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Placa Aterosclerótica/diagnóstico por imagemRESUMO
BACKGROUND AND OBJECTIVES: The complement system plays an important role in the development of acute coronary syndrome (ACS). Complement C1q is an important initial component of the classical complement pathway and closely related to many chronic inflammatory diseases, including atherosclerosis (AS). We aimed to determine whether there was association between serum complement C1q and the severity of coronary stenosis. SUBJECTS AND METHODS: 320 patients who underwent coronary arteriography (CAG) were stratified into non-ACS group (control group, nâ¯=â¯74), unstable angina group (UA group, nâ¯=â¯197) and acute myocardial infarction group (AMI group, nâ¯=â¯49) according to the severity of coronary stenosis and clinical manifestations. The severity of coronary stenosis was represented in Gensini score, and serum complement C1q level was compared using immunity transmission turbidity among three groups. RESULTS: The level of complement C1q in AMI group was lower significantly than control group and UA group (P < 0.05), but there was no correlation between serum complement C1q and Gensini score (ß=-0.086, Pâ¯=â¯0.125). In nitrate-taking patients, serum complement C1q had a negative association with Gensini score (r=-0.275, Pâ¯=â¯0.001), and in non-smokers, there was also a negative correlation (ß=-0.159, Pâ¯=â¯0.036). After calibrating smoking, drinking or statins, the serum complement C1q levels of control group, UA group and AMI group decreased in sequence (Pâ¯<⯠0.05). Logistic regression analysis showed that the decreasing of serum complement C1q was an unfavorable factor for acute myocardial infarction (OR=0.984, 95 %CI=0.972â¼0.997, Pâ¯=â¯0.015) and for ACS (OR=0.984, 95 %CI=0.971â¼0.984, Pâ¯=â¯0.025) in drinking patients. Regrettably, ROC curve suggested that the accuracy in diagnosing coronary atherosclerotic heart disease by serum complement C1q was low (AUC=0.568, 95 %CI= 0.492-0.644, Pâ¯=â¯0.076, sensitivity 73.6 %, specificity 58.1 %). CONCLUSION: Serum complement C1q in ACS patients, in particular AMI patients, showed lower level. This finding suggests further decrease of complement C1q level in ACS patients may be a contributory factor to instability or rupture of atherosclerotic plaques. Combined with other clinical indicators, it can be helpful to predict the risk and severity of coronary stenosis.
Assuntos
Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/imunologia , Complemento C1q/metabolismo , Síndrome Coronariana Aguda/etiologia , Idoso , Angina Instável/sangue , Angina Instável/complicações , Angina Instável/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Complemento C1q/deficiência , Estenose Coronária/sangue , Estenose Coronária/complicações , Estenose Coronária/imunologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações , Infarto do Miocárdio/imunologia , Placa Aterosclerótica/sangue , Placa Aterosclerótica/complicações , Placa Aterosclerótica/imunologia , Curva ROC , Fatores de Risco , Ruptura EspontâneaRESUMO
BACKGROUND: Kawasaki disease (KD) patients could develop coronary artery lesion (CAL) which threatens children's life. A previous study identified KD biomarker miRNAs that could discriminate KD patients from febrile non-KD patients. We wonder whether these KD prediction biomarkers could be further applied to predict CAL formation in KD patients. METHODS: To examine this hypothesis, we conducted a meta-analysis, miRNA mimic transfection, in vitro cell model and microarray assays. RESULTS: We first showed that miR-182-5p and miR-183-5p kept higher levels in the KD patients with CAL than those without CAL (p < .05). Further machine learning alignment confirmed that CAL formation could be predicted, with an auROC value of 0.86. We further treated neutrophil cells with miR-182-5p mimic, followed by in vitro transendotherial migration assay. As a result, miR-182-5p overexpression significantly (p < .05) enhanced neutrophil cells to infiltrate the endothelial layer composed of human coronary artery endothelium cells. Further microarray assay and pathway enrichment analysis showed that the genes activated with miR-182-5p overexpression were significantly enriched in the leukocyte transendothelial migration pathway (kegg_pathway_194, p < .05). CONCLUSION: Therefore, our study suggested that miR-182-5p enhanced in vitro leukocyte infiltration by activating the leukocyte transendothelial migration pathway in CAL formation in KD.
Assuntos
Estenose Coronária/imunologia , MicroRNAs/genética , Síndrome de Linfonodos Mucocutâneos/imunologia , Neutrófilos/citologia , Regulação para Cima , Criança , Pré-Escolar , Estenose Coronária/etiologia , Estenose Coronária/genética , Feminino , Redes Reguladoras de Genes , Marcadores Genéticos , Células HL-60 , Humanos , Aprendizado de Máquina , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/genética , Infiltração de Neutrófilos , Neutrófilos/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Migração Transendotelial e TransepitelialRESUMO
Inflammatory cells in atherosclerotic plaque exclusively originate from hematopoietic stem/progenitor cells (HSPCs). In this study, we investigated whether circulating HSPCs frequency related to coronary stenosis in patients with coronary heart disease (CHD). Coronary angiography was performed in 468 participants who were recruited at Cardiology Centre in LuHe Hospital from March 2016 to May 2017. Among these subjects, 344 underwent echocardiography. Mononuclear cells isolated from peripheral blood were stained with an antibody cocktail containing anti-human CD34, anti-human lineage, anti-human CD38, and anti-human CD45RA. Lineage-CD38-CD45RAdimCD34+HSPCs were quantified by flow cytometry. CHD was defined as coronary stenosis ≥50% and the extent of CHD was further categorised by coronary stenosis ≥70%. A p < 0.0031 was regarded statistically significant by the Bonferroni correction. Circulating HSPCs frequency was 1.8-fold higher in CHD patients than non-CHD participants (p = 0.047). Multivariate-adjusted logistic analysis demonstrated that HSPCs was the only marker that was associated with the odds ratio of having mild vs. severe coronary stenosis (2.08 (95% CI, 1.35-3.21), p = 0.0009). Left ventricular ejection fraction was inversely correlated with HSPCs frequency and CRP in CHD patients (p < 0.05 for both). In conclusion, HSPCs frequency in circulation is intimately related to coronary stenoses in CHD patients.
Assuntos
Estenose Coronária/diagnóstico por imagem , Células-Tronco Hematopoéticas/citologia , Monócitos/citologia , ADP-Ribosil Ciclase 1/metabolismo , Idoso , Antígenos CD34/metabolismo , Angiografia Coronária , Estenose Coronária/imunologia , Feminino , Citometria de Fluxo , Células-Tronco Hematopoéticas/imunologia , Humanos , Antígenos Comuns de Leucócito/metabolismo , Modelos Logísticos , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Monócitos/imunologiaRESUMO
The effect of 20 fatty acids in erythrocyte cell membranes on the extent of inflammatory response and cell oxidative stress was evaluated using multidimensional statistical data analysis in 54 patients suffering from ischemic heart disease undergoing percutaneous coronary intervention with coronary stent implantation using multidimensional statistical data analysis. A systemic inflammatory response was indicated by an increase of C-reactive protein (CRP), serum amyloid A (SAA) and ceruloplasmin 48 h after stent implantation and by an increase of interleukin-6 (IL-6) 24 h after intervention. The increase of malondialdehyde (MDA) after 48 h was used as a marker of cell damage by oxidative stress. Multiple linear regression revealed statistically significant relationships between concentration of some fatty acids and the magnitude of inflammatory response, or oxidative stress, after stent implantation. The most significant relationship with an increase of plasma CRP was found for myristic acid and, to a lesser extent, for oleic acid. Trans octadecenoic acid, and to a lesser extent palmitooleic and nervonic fatty acids were found in inverse correlation with the CRP increase. The increase of IL-6 showed a statistically significant correlation with myristic acid, to a lesser extent with cis-9-eicosenoic acid and to the least extent with docosahexaenoic acid, inversely with pentadecanoic, γ-linolenic and stearic acids. An increase of oxidative stress (MDA) significantly correlated only with γ-linolenic acid. Other studied markers of inflammatory response to coronary stenting were SAA and ceruloplasmin (Cp). Statistical evaluation revealed that SAA and Cp are not suitable markers for assessment relationships between inflammation and erythrocyte membrane fatty acids.
Assuntos
Estenose Coronária/terapia , Membrana Eritrocítica/imunologia , Eritrócitos/imunologia , Ácidos Graxos/metabolismo , Intervenção Coronária Percutânea , Stents , Biomarcadores/sangue , Proteína C-Reativa/análise , Estenose Coronária/sangue , Estenose Coronária/imunologia , Estudos Transversais , Membrana Eritrocítica/metabolismo , Eritrócitos/metabolismo , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/imunologia , Proteína Amiloide A Sérica/análiseAssuntos
Arterite , Doença da Artéria Coronariana , Oclusão Coronária , Estenose Coronária , Idoso , Arterite/diagnóstico por imagem , Arterite/imunologia , Arterite/cirurgia , Biópsia , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Ponte de Artéria Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/cirurgia , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/imunologia , Oclusão Coronária/cirurgia , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/imunologia , Estenose Coronária/cirurgia , Feminino , Humanos , Imunoglobulina G/imunologia , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Periodontitis, a common polymicrobial inflammatory disease in the tooth supporting tissues, is a risk factor for coronary artery disease. One of the proposed underlying mechanisms is the systemic immune response to periodontal infection. We studied how serum antibodies against seven periodontal pathogens and their subgingival levels associate with each other, periodontitis, and coronary artery disease. METHODS: The Parogene cohort included 505 Finnish patients (mean age 63 y) who underwent coronary angiography, and clinical and radiographic oral examinations. Coronary diagnosis was defined as no significant coronary artery disease (<50% stenosis, n = 152), stable coronary artery disease (≥50% stenosis, n = 184) and acute coronary syndrome (n = 169). Levels of subgingival Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, Tannerella forsythia, Campylobacter rectus, and Fusobacterium nucleatum were determined by checkerboard DNA-DNA hybridization. Serum antibody (IgA/IgG) levels were analyzed with enzyme-linked immunosorbent assay (ELISA). Aggregate IgA/IgG burdens were calculated by summing and standardizing the serum antibody levels. RESULTS: Patients with active periodontitis were characterized by higher levels of subgingival bacteria and corresponding IgA/IgG response. Quartiles 2-4 of serum IgA/IgG burden indicated higher risk for acute coronary syndrome (OR 1.84, 95%CI 1.01-3.35 for IgA; OR 1.87, 95%CI 1.01-3.46 for IgG) independently of established cardiovascular risk factors, body mass index, number of teeth, subgingival bacterial levels and periodontal diagnosis. CONCLUSIONS: Our findings support the hypothesis that the association between periodontitis and cardiovascular diseases is partly mediated by the immunologic response for periodontal pathogens.
Assuntos
Síndrome Coronariana Aguda/imunologia , Anticorpos Antibacterianos/sangue , Bactérias/imunologia , Doença da Artéria Coronariana/imunologia , Estenose Coronária/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Periodontite/imunologia , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/microbiologia , Idoso , Carga Bacteriana , Técnicas Bacteriológicas , Biomarcadores/sangue , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/microbiologia , Estenose Coronária/sangue , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/microbiologia , Estudos Transversais , Feminino , Finlândia , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Periodontite/sangue , Periodontite/diagnóstico , Periodontite/microbiologia , Fatores de RiscoRESUMO
Circulating leukocyte subtypes and monocyte subsets are independent predictors of cardiovascular events. We hypothesized that an increased leukocyte subtype would predict severe coronary stenosis and extensive plaque involvement. We retrospectively analyzed clinical, laboratory, and coronary CT data in a total of 588 asymptomatic adults (69% men; mean age, 57 ± 9 years) undergoing a general health check-up. Intermediate CD14++CD16+ monocyte count had the strongest association with mixed and calcified plaque scores, whereas the numbers of neutrophils and classical CD14++CD16- monocytes were significantly associated with non-calcified plaque score. Only high CD14++CD16+ monocyte count (>12 cells/µL) significantly predicted extensive plaque involvement [odds ratio 3.16 (95% confidence interval 1.84-5.43), P < 0.001; quartile 4 vs. 1-3] and severe coronary stenosis [3.67 (1.84-7.33), P < 0.001; quartile 4 vs. 1-3] after adjustments for Framingham Risk Score (FRS), metabolic syndrome, and C-reactive protein. The CD14++CD16+ monocyte count, when added to FRS, significantly reclassified 30.4 and 26.7% of the overall and 50.2 and 36.2% of the intermediate-risk population (FRS 6-20%) for predicting extensive plaque involvement and severe coronary stenosis, respectively. Thus, in asymptomatic individuals, intermediate CD14++CD16+ monocyte could independently predict severe CAD and improve risk stratification.
Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Estenose Coronária/imunologia , Vasos Coronários/diagnóstico por imagem , Receptores de Lipopolissacarídeos/sangue , Monócitos/imunologia , Tomografia Computadorizada Multidetectores , Placa Aterosclerótica , Receptores de IgG/sangue , Idoso , Doenças Assintomáticas , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Estenose Coronária/sangue , Estenose Coronária/diagnóstico por imagem , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Contagem de Leucócitos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Calcificação Vascular/sangue , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/imunologiaRESUMO
BACKGROUND: The macrophage polarization is proposed to be involved in initial events and remodeling of atherosclerosis plaques. Mannose receptor, C type 1 (MRC1) is a trans-membrane glycoprotein participating in phagocytosis and, is highly expressed in the M2 macrophages. OBJECTIVE: The aim of this study was to investigate the effects of sdLDL (small dense LDL) on the MRC1 gene expression level and secretion of histamine in the differentiated M2 macrophages from monocytes of patients with coronary artery stenosis and healthy subjects. METHOD: The monocytes were isolated from healthy subjects (< 5% stenosis) and patients (> 70% stenosis, SVD (Single Vessel Disease), 2VD (Two-Vessel Disease) and 3VD (Three-Vessel Disease)) by RosetteSep kit and, were differentiated into M2 macrophages by macrophage colonystimulating factor (M-CSF). The sdLDL particles were obtained by PEG-combined precipitation method. The MRC1 gene expression and histamine levels were measured by RT-qPCR and ELISA techniques, respectively. RESULTS: The MRC1 gene expression level was significantly increased in M2 macrophages of healthy subjects (P=0.05) while it reduced in SVD (P=0.05), 2VD (P=0.01) and 3VD (P=0.9) patients after treatment with sdLDL. The histamine value secreted from M2 macrophages (7-day) was higher (>3-fold, P=0.02) in patients as compared to healthy controls. CONCLUSION: The results showed that the sdLDL particles reduce the MRC1 gene expression levels in the differentiated M2 macrophages from patients with coronary artery disease. Furthermore, they had high inflammatory capacity for the secretion of histamine.
Assuntos
Estenose Coronária/genética , Regulação para Baixo , Histamina/imunologia , Lipoproteínas LDL/imunologia , Macrófagos/imunologia , Receptores Imunológicos/genética , Polaridade Celular , Células Cultivadas , Estenose Coronária/imunologia , Estenose Coronária/patologia , Humanos , Macrófagos/citologia , Macrófagos/patologia , Glicoproteínas de Membrana , Fagocitose , Receptores Imunológicos/imunologiaRESUMO
We evaluated immune activation and coronary artery plaque in young adults with human immunodeficiency virus acquired in early life (n = 31). Coronary plaque was positively associated with lipids, immune activation marker %CD8+CD38+DR+ and E-selectin, a marker of endothelial inflammation. Immune activation and endothelial inflammation may drive coronary plaque formation during the early stages of atherosclerosis in the context of chronic human immunodeficiency virus.
Assuntos
Estenose Coronária/complicações , Infecções por HIV , Adulto , Contagem de Linfócito CD4 , Relação CD4-CD8 , Estudos de Casos e Controles , HDL-Colesterol/sangue , Estenose Coronária/epidemiologia , Estenose Coronária/imunologia , Selectina E/sangue , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Humanos , Ativação Linfocitária/imunologia , Masculino , Placa Aterosclerótica , Adulto JovemAssuntos
Arterite/diagnóstico por imagem , Doenças Autoimunes/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Imunoglobulina G/imunologia , Idoso , Arterite/patologia , Doenças Autoimunes/patologia , Biópsia por Agulha , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/patologia , Angiografia Coronária/métodos , Estenose Coronária/imunologia , Estenose Coronária/patologia , Progressão da Doença , Evolução Fatal , Humanos , Imunoglobulina G/sangue , Imuno-Histoquímica , Imageamento por Ressonância Magnética/métodos , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Medição de RiscoRESUMO
A 76-year-old woman with multiple coronary risk factors was admitted to our hospital because of episodes of new-onset chest pain that had begun 3 days previously. She underwent percutaneous coronary intervention (PCI) for severe stenoses in the two high lateral (HL) branches. Intravascular ultrasound (IVUS) revealed massive stenotic lesions in the HL branches and tumorous nonstenotic lesions in the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (LCx). iMAP™, optical coherence tomography (OCT), and coronary computed tomography angiography (CCTA) were performed. iMAP depicted fibrosis in the vessel (green areas) and nonfibrotic tissue change suggestive of inflammation outside the vessel (yellow/red areas). OCT revealed high-intensity homogenous intimal hyperplasia with superficial calcification, and CCTA showed massive periarterial soft lesions in the HL, LAD, and LCx. The serum IgG4 level was high at 252-427 mg/dL (8 measurements) (reference range, 4.8-105.0 mg/dL). We suspected IgG4-related coronary periarteritis on the basis of the comprehensive diagnostic criteria as a possible diagnosis. The clinical course was good after initial and subsequent PCIs for both the HL stenoses and the progressing LCx stenosis, and there was no recurrence of angina pectoris thereafter. Steroids were not administered because the massive lesions did not enlarge during the 16 months of follow-up. iMAP was able to evaluate the tissue characteristics of tumorous lesions in the stenosed HL branches and the nonstenotic LAD and LCx in a patient with an elevated level of IgG4.
Assuntos
Arterite/diagnóstico por imagem , Doenças Autoimunes/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Imunoglobulina G/sangue , Ultrassonografia de Intervenção/métodos , Idoso , Angioplastia Coronária com Balão , Arterite/sangue , Arterite/imunologia , Arterite/terapia , Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Biomarcadores/sangue , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/terapia , Estenose Coronária/sangue , Estenose Coronária/imunologia , Estenose Coronária/terapia , Feminino , Humanos , Valor Preditivo dos Testes , Tomografia de Coerência Óptica , Resultado do TratamentoRESUMO
BACKGROUND: Heightened immune activation among human immunodeficiency virus (HIV)-infected persons may contribute to atherosclerosis. We assessed associations of serologic markers of monocyte activation, soluble CD163 (sCD163) and soluble CD14 (sCD14), and monocyte chemoattractant protein 1 (CCL2) with subclinical atherosclerosis among men with and those without HIV infection in the Multicenter AIDS Cohort Study. METHODS: We performed noncontrast computed tomography on 906 men (566 HIV-infected men and 340 HIV-uninfected men), 709 of whom also underwent coronary computed tomographic angiography. Associations between each biomarker and the prevalence of coronary plaque, the prevalence of stenosis of ≥50%, and the extent of plaque were assessed by logistic and linear regression, adjusting for age, race, HIV serostatus, and cardiovascular risk factors. RESULTS: Levels of all biomarkers were higher among HIV-infected men, of whom 81% had undetectable HIV RNA, and were associated with lower CD4(+) T-cell counts. In the entire population and among HIV-infected men, higher biomarker levels were associated with a greater prevalence of coronary artery stenosis of ≥50%. Higher sCD163 levels were also associated with greater prevalences of coronary artery calcium, mixed plaque, and calcified plaque; higher CCL2 levels were associated with a greater extent of noncalcified plaque. CONCLUSIONS: sCD163, sCD14, and CCL2 levels were elevated in treated HIV-infected men and associated with atherosclerosis. Monocyte activation may increase the risk for cardiovascular disease in individuals with HIV infection.
Assuntos
Aterosclerose/imunologia , Biomarcadores/metabolismo , Infecções por HIV/imunologia , Monócitos/imunologia , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/imunologia , Antígenos de Diferenciação Mielomonocítica/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Cálcio/metabolismo , Quimiocina CCL2/imunologia , Quimiocina CCL2/metabolismo , Estudos de Coortes , Angiografia Coronária/métodos , Estenose Coronária/imunologia , Estenose Coronária/metabolismo , Infecções por HIV/metabolismo , Humanos , Receptores de Lipopolissacarídeos/imunologia , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Placa Aterosclerótica/imunologia , Placa Aterosclerótica/metabolismo , Prevalência , Receptores de Superfície Celular/imunologia , Receptores de Superfície Celular/metabolismo , Fatores de Risco , Tomografia Computadorizada por Raios X/métodosRESUMO
Low anti-phosphorylcholine (PC) IgM plasma levels have been associated with increased incidence of adverse events in coronary artery disease (CAD). The underlying mechanisms are unclear. We hypothesized that atheroprotection mediated by anti-PC IgM antibodies is associated with reduced vascular remodeling and therefore tested whether anti-PC IgM plasma levels independently predict vascular remodeling. In a prospective cross-sectional study, anti-PC IgM plasma levels were measured in 175 consecutive patients with suspected CAD undergoing cardiac computed tomography angiography. Plaque morphology was thoroughly analyzed. Vascular remodeling was defined by a change in the vessel diameter at the plaque site in comparison to the reference segment proximal to the lesion (reference diameter) of ≥10%. Mean age of the patients was 64.8 ± 10.7 years, 48.6% were female. In 98 patients CAD was diagnosed, 57 (58.2%) of which displayed non-obstructive CAD (stenosis <50%), whereas 41 (41.8%) exhibited obstructive CAD (stenosis ≥50%). In 34 of 98 (34.7%) CAD patients vascular remodeling was present. Mean anti-PC IgM levels did not differ between patients with and without CAD (70.8 ± 52.7 vs. 69.1 ± 55.1 U/mL). However, anti-PC IgM levels were significantly lower in CAD patients compared to those without vascular remodeling (46.6 ± 31.6 vs. 73.3 ± 58.5 U/mL, P = 0.024). Using multivariate logistic regression, anti-PC IgM plasma levels independently predicted coronary vascular remodeling (HR 0.322, 95% confidence interval 0.121-0.856, P = 0.023). In conclusion, low anti-PC IgM levels are independently associated with coronary vascular remodeling. These findings may represent the link between in vitro studies demonstrating atheroprotective effects of anti-PC IgM and clinical data demonstrating that low anti-PC IgM levels are associated with adverse outcome in CAD patients.
Assuntos
Autoanticorpos/sangue , Doença da Artéria Coronariana/diagnóstico , Estenose Coronária/diagnóstico , Vasos Coronários/patologia , Imunoglobulina M/sangue , Fosforilcolina/imunologia , Remodelação Vascular , Idoso , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Angiografia Coronária/métodos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/patologia , Estenose Coronária/sangue , Estenose Coronária/imunologia , Estenose Coronária/patologia , Estudos Transversais , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Análise Multivariada , Variações Dependentes do Observador , Placa Aterosclerótica , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
This study aimed to investigate the relation between the neutrophil-to-lymphocyte ratio (NLR) and the severity of coronary artery stenosis. A total of 219 patients were included in the study, comprising 51 coronary artery atherosclerosis (CAC) patients, 92 stable angina pectoris (SAP) patients, and 76 acute coronary syndrome (ACS) patients. Based on the results of coronary angiography, all patients were divided into two groups according to the Gensini scores: the low-score group (N = 142) and the high-score group (N = 77). The NLR was computed from the ratio of neutrophils and lymphocytes from the complete blood count. The association between the NLR and severity of coronary artery disease was assessed using correlation analysis and logistic regression. The NLR was higher in ACS patients than in SAP and CAC patients (P < 0.05). In addition, the NLR was higher in the high-score group than in the low-score group (P < 0.05). Correlation analysis showed that the NLR was significantly correlated with the Gensini score. After multivariate analysis, high NLRs were independent predictors of high Gensini scores, together with age and high-density lipoprotein. A cutoff NLR of 2.385 predicted high Gensini scores with a sensitivity and specificity of 64 and 63%, respectively. The study suggests that the NLR is an independent predictor of coronary heart disease that may be useful for predicting the severity of coronary artery stenosis.
Assuntos
Estenose Coronária/imunologia , Estenose Coronária/patologia , Linfócitos/citologia , Neutrófilos/citologia , Índice de Gravidade de Doença , Contagem de Células , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROCRESUMO
OBJECTIVE: The SYNTAX Score was recently developed to characterize the coronary vasculature with respect to the number of lesion's location, complexity, and functional impact and it is a quantitative scoring system to assist with patient selection for optimal revascularization strategy between percutaneous coronary intervention (PCI) and coronary artery by-pass surgery (CABG). b2-glycoprotein I (b2GPI), a plasma protein that binds cardiolipin, acts as a modulator of platelet aggregation and coagulation. Antibodies to b2GPI may have a role in atherosclerosis by inducing endothelial cell activation. We investigated the relationship between anti beta 2 GPI and severity of coronary artery stenosis by calculating the SYNTAX Score among patients undergoing CABG surgery. PATIENTS AND METHODS: We prospectively investigate 612 patients who undergo elective coronary angiography between September 2012 and June 2013. Patients were evaluated for blood chemistry and anti-b2GPI IgA, IgM and IgG. Ninety seven patients with complete biochemical analysis including anti Beta 2 GPI antibodies and undergone CABG have been enrolled in this study. We divided patients in to 2 groups according to the SYNTAX scores. Group 1 included 48 patients with low SYNTAX scores (<23) and group 2 included 49 patients with intermediate and high SYNTAX scores (>23). RESULTS: There was significant correlation between elevated anti b2GPI IgG levels and higher SYNTAX score which indicate advanced and complex CAD. In this study, lesion complexity increased progressively with increasing anti-b2GPI-IgG type of antibody levels. According to this findings, anti-b2GPI-IgG is a strong predictor of higher SYNTAX score. CONCLUSIONS: In addition to the traditional risk factors for atherosclerosis, the proinflammatory and procoagulant activities of antiphospholipid antibodies appear to be important risk factors for atherosclerotic occlusive disease.