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1.
Medicine (Baltimore) ; 99(38): e22126, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957332

RESUMO

INTRODUCTION: Coronary microvascular disease (CMVD) can affect the structure, function, and metabolism of the heart, and has an important impact on the occurrence, development and prognosis of coronary artery disease (CAD). Shexiang Tongxin dropping pill (STDP) can dilate blood vessels, alleviate inflammation, reduce endothelial damage, and improve coronary microvascular function in mice with myocardial infarction. This study aims to assess the impact of STDP on stable coronary artery disease (SCAD) patients with normal FFR and CMVD. METHODS AND ANALYSIS: This is a single-center, prospective randomized trial that will enroll 64 SCAD patients, CAD with normal FFR and CMVD. Patients will be randomly divided into study group and control group in a 1:1 fashion. On the basis of conventional drug treatment, the former will receive STDP while the latter will not. The follow-up period of the subjects is 12 months, and clinical follow-up will be conducted before discharge, 30 days, 3 months, 6 months, and 12 months after procedure to complete the detection of relevant indicators. The primary endpoint is the change of index of microcirculatory resistance (ΔIMR) at 12-month follow-up. DISCUSSION: The present study will be the first randomized control study to evaluate the efficacy and safety of STDP on SCAD patients, CAD with normal FFR and CMVD, which will provide a broader idea and more experimental basis for improving the treatment of CMVD. TRIAL REGISTRATION: This is a protocol for the randomized clinical trial which has been registered in the Chinese clinical Trial Registry with an identifier: ChiCTR2000032429.


Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/patologia , Medicamentos de Ervas Chinesas , Microvasos/patologia , Circulação Coronária , Reserva Fracionada de Fluxo Miocárdico , Humanos , Microcirculação , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Arterioscler Thromb Vasc Biol ; 40(9): 2095-2107, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32757647

RESUMO

OBJECTIVE: Apo (apolipoprotein) CIII mediates the metabolism of triglyceride (TG)-rich lipoproteins. High levels of plasma apoCIII are positively correlated with the plasma TG levels and increase the cardiovascular risk. However, whether apoCIII is directly involved in the development of atherosclerosis has not been fully elucidated. Approach and Results: To examine the possible roles of apoCIII in lipoprotein metabolism and atherosclerosis, we generated apoCIII KO (knockout) rabbits using ZFN (zinc finger nuclease) technique. On a normal standard diet, apoCIII KO rabbits exhibited significantly lower plasma levels of TG than those of WT (wild type) rabbits while total cholesterol and HDL (high-density lipoprotein) cholesterol levels were unchanged. Analysis of lipoproteins isolated by sequential ultracentrifugation revealed that reduced plasma TG levels in KO rabbits were accompanied by prominent reduction of VLDLs (very-low-density lipoproteins) and IDLs (intermediate-density lipoproteins). In addition, KO rabbits showed faster TG clearance rate after intravenous fat load than WT rabbits. On a cholesterol-rich diet, KO rabbits exhibited constantly and significantly lower levels of plasma total cholesterol and TG than WT rabbits, which was caused by a remarkable reduction of ß-VLDLs-the major atherogenic lipoproteins. ß-VLDLs of KO rabbits showed higher uptake by cultured hepatocytes and were cleared faster from the circulation than ß-VLDLs isolated from WT rabbits. Both aortic and coronary atherosclerosis was significantly reduced in KO rabbits compared with WT rabbits. CONCLUSIONS: These results indicate that apoCIII deficiency facilitates TG-rich lipoprotein catabolism, and therapeutic inhibition of apoCIII expression may become a novel means not only for the treatment of hyperlipidemia but also for atherosclerosis.


Assuntos
Doenças da Aorta/prevenção & controle , Apolipoproteína C-III/deficiência , Aterosclerose/prevenção & controle , Doença da Artéria Coronariana/prevenção & controle , Triglicerídeos/sangue , Animais , Animais Geneticamente Modificados , Doenças da Aorta/genética , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Apolipoproteína C-III/genética , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Biomarcadores/sangue , HDL-Colesterol/sangue , VLDL-Colesterol/sangue , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Modelos Animais de Doenças , Feminino , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Lipoproteínas IDL/sangue , Fígado/metabolismo , Masculino , Oxirredução , Placa Aterosclerótica , Coelhos
3.
Br J Radiol ; 93(1114): 20200540, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32706985

RESUMO

OBJECTIVE: This study sought to investigate the association between volume and attenuation of epicardial fat and presence of obstructive coronary artery disease (CAD) and high-risk plaque features (HRPF) on CT angiography (CTA) in patients with atypical chest pain and whether the association, if any, is independent of conventional cardiovascular risk factors and coronary artery calcium score (CACS). METHODS: Patients referred for coronary CTA with atypical chest pain and clinical suspicion of CAD were included in the study. Quantification of CACS, epicardial fat volume (EFV) and epicardial fat attenuation (EFat) was performed on non-contrast images. CTA was evaluated for presence of obstructive CAD and presence of HRPF. RESULTS: 255 patients (median age [interquartile range; IQR]: 51[41-60] years, 51.8% males) were included. On CTA, CAD, obstructive CAD (≥50% stenosis) and CTA-derived HRPFs was present in 133 (52.2%), 37 (14.5%) and 82 (32.2%) patients respectively. A significantly lower EFat was seen in patients with obstructive CAD than in those without (-86HU [IQR:-88 to -82 HU] vs -84 [IQR:-87 HU to -82 HU]; p = 0.0486) and in patients with HRPF compared to those without (-86 HU [IQR:-88 to -83 HU] vs -83 HU [-86 HU to -81.750 HU]; p < 0.0001). EFat showed significant association with obstructive CAD (unadjusted Odd's ratio (OR) [95% CI]: 0.90 [0.81-0.99];p = 0.0248) and HRPF (unadjusted OR [95% CI]: 0.83 [0.76-0.90];p < 0.0001) in univariate analysis, which remained significant in multivariate analysis. However, EFV did not show any significant association with neither obstructive CAD nor HRPF in multivariate analysis. Adding EFat to conventional coronary risk factors and CACS in the pre-test probability models increased the area-under curve (AUC) for prediction of both obstructive CAD (AUC[95% CI]: 0.76 [0.70-0.81] vs 0.71 [0.65-0.77)) and HRPF (AUC [95% CI]: 0.92 [0.88-0.95] vs 0.89 [0.85-0.93]), although not reaching statistical significance. CONCLUSION: EFat, but not EFV, is an independent predictor of obstructive CAD and HRPF. Addition of EFat to traditional cardiovascular risk factors and CACS improves estimation for pretest probability of obstructive CAD and HRPF. ADVANCES IN KNOWLEDGE: EFat is an important attribute of epicardial fat as it reflects the "quality" of fat, taking into account the effects of brown-white fat transformation and fibrosis, as opposed to mere evaluation of "quantity" of fat by EFV. Our study shows that EFat is a better predictor of obstructive CAD and HRPF than EFV and can thus explain the inconsistent association of increased EFV alone with CAD.


Assuntos
Tecido Adiposo/patologia , Dor no Peito , Doença da Artéria Coronariana/patologia , Pericárdio/patologia , Placa Aterosclerótica/patologia , Tecido Adiposo/diagnóstico por imagem , Adulto , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Pericárdio/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco
4.
DNA Cell Biol ; 39(9): 1678-1684, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32716219

RESUMO

Coronary artery disease (CAD) is the main cause of death worldwide. Atherosclerosis, the leading underlying cause of CAD, is a progressive inflammatory disease. miRNAs play a substantial role in inflammation. The aim of this study was to investigate the associations of peripheral blood mononuclear cells (PBMCs) gene expression of IP10 and miRNA 296-a and serum levels of IP10 and serum inflammatory cytokines interleukin-6 (IL-6) in CAD patients and controls. This is a case-control study conducted on 82 angiography confirmed CAD patients and 82 controls. PBMC expressions of miR-296a and IP10 were evaluated by real-time method, and serum concentrations of IL-6 and TNF-α were evaluated by enzyme-linked immunosorbent assay in the study population. A significant increase was found for serum IP10, IL-6, and TNF-α levels, and PBMC expression of IP10 and miRNA 296-a genes expression of CAD as comparison with controls. No significant correlation was found between IP10 gene expression and miRNA 296-a. A significant positive correlation was found between PBMC gene expression level of IP10 and serum concentrations of IP10 and cytokines IL-6 and TNF-α levels. Taking together, in PBMC of CAD patients, the IP10 and 296-a miRNA genes expression levels were increased significantly than controls. IP10, IL-6, and TNF-α levels in CAD patients were more than those in controls significantly. Concerning positive relationship between miRNA 296-a gene expression level and serum concentrations of IL-6 and TNF-α in CAD patients, it is proposed that IL-6 and TNF-α inhibitor could be the main targets of miRNA 296a and, thereby the IL-6 and TNF-α levels were increased; however, further study is needed.


Assuntos
Doença da Artéria Coronariana/sangue , MicroRNAs/sangue , Receptores de Citocinas/sangue , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Interleucina-6/sangue , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Monócitos/metabolismo , Receptores de Citocinas/genética , Receptores de Citocinas/metabolismo , Fator de Necrose Tumoral alfa/sangue
5.
Arterioscler Thromb Vasc Biol ; 40(9): 1982-1989, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32673526

RESUMO

Atherosclerosis is a systemic disease that involves multiple vascular beds. The pathological characteristics and clinical presentation, however, vary among the different vascular territories. Acute coronary syndrome is a relatively common manifestation of coronary atherosclerotic disease, wherein the thrombosis occurs secondary to disruption (65%-75%) and erosion (25%-35%) of the fibrous caps of atheromatous plaques. The plaques associated with plaque rupture have large necrotic cores and thin and inflamed fibrous caps. However, the pathological manifestations of peripheral artery disease result from thrombosis regardless of the extent of atherosclerosis. Approximately 75% of peripheral arteries with significant stenosis demonstrate presence of thrombi, of which two-thirds have thrombi associated with insignificant atherosclerosis. The presence of obliterative thrombi in peripheral arteries of patients with critical limb ischemia in the absence of coronary artery-like lesions suggests a locally thrombogenic or remotely embolic basis of disease. Extensive calcification of the medial vascular layer is commonly observed. In this review, we have described and compared the pathological basis of coronary and peripheral artery disease in patients with acute coronary syndrome and critical limb ischemia. It is expected that pathogenetic characterization would allow for definition of strategic targets for superior management of peripheral artery disease.


Assuntos
Síndrome Coronariana Aguda/patologia , Artérias/patologia , Doença da Artéria Coronariana/patologia , Isquemia/patologia , Doença Arterial Periférica/patologia , Placa Aterosclerótica , Trombose/patologia , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/epidemiologia , Artérias/efeitos dos fármacos , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/epidemiologia , Vasos Coronários/patologia , Estado Terminal , Progressão da Doença , Fibrinolíticos/uso terapêutico , Fibrose , Humanos , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/epidemiologia , Prognóstico , Ruptura Espontânea , Trombose/tratamento farmacológico , Trombose/epidemiologia
6.
Medicine (Baltimore) ; 99(27): e20794, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629663

RESUMO

BACKGROUND: Recently, trimethylamine N-oxide (TMAO) unexplained gut microbe has been proposed as a promising risk factor for atherosclerotic cardiovascular disease (CVD) pathogenesis and adverse events. The relationship of TMAO with coronary atherosclerotic burden has been evaluated in patients with stable coronary artery disease and ST-segment elevation myocardial infarction, but still needs to be explored in newly diagnosed non-ST-segment elevation myocardial infarction (NSTEMI) patients. MATERIAL AND METHODS: A prospective, single-center, SZ-NSTEMI trial (ChiCTR1900022366) is underway to investigate the relationship of TMAO with the severity and prognosis of coronary atherosclerosis in newly diagnosed NSTEMI patients who will undergo coronary angiography with primary percutaneous coronary intervention (pPCI). The primary endpoint of the study will be assessed the association of TMAO with coronary atherosclerotic severity quantify by the number of diseased coronary arteries and SYNTAX score after the coronary angiography. The secondary endpoints will be identified the TMAO as a prognostic biomarker for the short (1 month) and long-term (12 months) major cardiovascular and cerebrovascular events (MACCEs) rate including myocardial infarction, target vessel revascularization, stroke, heart failure, all-cause rehospitalization, and all-cause mortality after the pPCI. The blood samples will be collected from each patient before the procedure to measure the TMAO by isotope dilution high-performance liquid chromatography. In conclusion, SZ-NSTEMI will be the first cohort that will be investigated the association of TMAO with the severity and prognosis of coronary atherosclerotic burden in NSTEMI patients, aiming to identify TMAO as a predictor and a prognostic biomarker.


Assuntos
Aterosclerose/patologia , Doença da Artéria Coronariana/patologia , Metilaminas/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/patologia , Adolescente , Adulto , Idoso , Biomarcadores , Doenças Cardiovasculares/patologia , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
7.
PLoS One ; 15(6): e0233791, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584909

RESUMO

BACKGROUND: Machine learning (ML) is able to extract patterns and develop algorithms to construct data-driven models. We use ML models to gain insight into the relative importance of variables to predict obstructive coronary artery disease (CAD) using the Coronary Computed Tomographic Angiography for Selective Cardiac Catheterization (CONSERVE) study, as well as to compare prediction of obstructive CAD to the CAD consortium clinical score (CAD2). We further perform ML analysis to gain insight into the role of imaging and clinical variables for revascularization. METHODS: For prediction of obstructive CAD, the entire ICA arm of the study, comprising 719 patients was used. For revascularization, 1,028 patients were randomized to invasive coronary angiography (ICA) or coronary computed tomographic angiography (CCTA). Data was randomly split into 80% training 20% test sets for building and validation. Models used extreme gradient boosting (XGBoost). RESULTS: Mean age was 60.6 ± 11.5 years and 64.3% were female. For the prediction of obstructive CAD, the AUC was significantly higher for ML at 0.779 (95% CI: 0.672-0.886) than for CAD2 (0.696 [95% CI: 0.594-0.798]) (P = 0.01). BMI, age, and angina severity were the most important variables. For revascularization, the model obtained an overall area under the receiver-operation curve (AUC) of 0.958 (95% CI = 0.933-0.983). Performance did not differ whether the imaging parameters used were from ICA (AUC 0.947, 95% CI = 0.903-0.990) or CCTA (AUC 0.941, 95% CI = 0.895-0.988) (P = 0.90). The ML model obtained sensitivity and specificity of 89.2% and 92.9%, respectively. Number of vessels with ≥70% stenosis, maximum segment stenosis severity (SSS) and body mass index (BMI) were the most important variables. Exclusion of imaging variables resulted in performance deterioration, with an AUC of 0.705 (95% CI 0.614-0.795) (P <0.0001). CONCLUSIONS: For obstructive CAD, the ML model outperformed CAD2. BMI is an important variable, although currently not included in most scores. In this ML model, imaging variables were most associated with revascularization. Imaging modality did not influence model performance. Removal of imaging variables reduced model performance.


Assuntos
Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Aprendizado de Máquina , Revascularização Miocárdica/estatística & dados numéricos , Idoso , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos
8.
Angiology ; 71(9): 840-846, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32519552

RESUMO

We investigated the relationship between C-reactive protein-to-albumin ratio (CAR) and coronary artery ectasia (CAE). The retrospective study population included 150 patients with isolated CAE, 150 with obstructive coronary artery disease (CAD), and 150 with a normal coronary artery angiogram (NCA). The severity of isolated CAE was determined according to the Markis classification. C-reactive protein-to-albumin ratio was significantly higher in patients with isolated CAE than in those with obstructive CAD and NCA (10.5 [5.9-30.9], 5.7 [1.8-13.2] and 3.0 [0.9-8.9], respectively). Logistic regression analysis showed that CAR (odds ratio [OR]: 3.054, 95% CI: 1.021-9.165, P = .001), platelet-to-lymphocyte ratio (PLR; OR: 1.330, 95% CI: 1.025-1.694, P = .044), and monocyte-to-high density cholesterol ratio (MHR; OR: 1.031, 95% CI: 1.009-1.054, P = .006) were independently associated with the presence of isolated CAE. Receiver operating characteristic curve analysis showed that CAR (area under the curve [AUC] ± standard error [SE] = 0.838 ± 0.016; P < .001) had a stronger diagnostic value for detecting significant CAE than PLR (AUC ± SE = 0.632 ± 0.023) and MHR (AUC ± SE = 0.726 ± 0.022). C-reactive protein-to-albumin ratio had a significantly strong correlation with the severity of isolated CAE (r = 0.536, P < .001). To the best of our knowledge, this study showed for the first time that CAR was significantly associated with CAE presence and severity.


Assuntos
Proteína C-Reativa/metabolismo , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Albumina Sérica/metabolismo , Idoso , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Dilatação Patológica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença
9.
PLoS One ; 15(5): e0232483, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392256

RESUMO

BACKGROUND: Percutaneous coronary intervention represents the most important treatment modality of coronary artery stenosis. In-stent restenosis (ISR) is still a limitation for the long-term outcome despite the introduction of drug eluting stents. It has been shown that adipokines directly influence vessel wall homeostasis by influencing the function of endothelial cells and arterial smooth muscle cells. Visceral adipose tissue-derived serpin vaspin was recently identified as a member of serine protease inhibitor family and serveral studies could demonstrate a relation to metabolic diseases. The aim of this study was to investigate a role of vaspin in the development of in-stent restenosis in vivo and on migration of smooth muscle cells and endothelial cells in vitro. METHODS: We studied 85 patients with stable coronary artery disease who underwent elective and successful PCI with implatation of drug eluting stents. Blood samples were taken directly before PCI. Vaspin plasma levels were measured by specific ELISA. ISR was evaluated eight months later by coronary angiography. Human coronary artery smooth muscle cells (HCASMC) and human umbilical vein endothelial cells (HUVEC) migration was analyzed by an in-vitro migration assay with different concentrations (0.004ng/mL up to 40ng/mL) of vaspin as well as by an scratch assay. For proliferation an impedance measurement with specialiced E-Plates was performed. RESULTS: During the follow up period, 14 patients developed ISR. Patients with ISR had significantly lower vaspin plasma levels compared to patients without ISR (0.213 ng/ml vs 0.382 ng/ml; p = 0.001). In patients with plasma vaspin levels above 1.35 ng/ml we could not observe any restenosis. There was also a significant correlation of plasma vaspin levels and late lumen loss in the stented coronary segments. Further we could demonstrate that vaspin nearly abolishes serum induced migration of HCASMC (100% vs. 9%; p<0.001) in a biphasic manner but not migration of HUVEC. Proliferation of HCASMC and HUVEC was not modulated by vaspin treatment. CONCLUSION: We were able to show that the adipokine vaspin selectively inhibits human coronary SMC migration in vitro and has no effect on HUVEC migration. Vaspin had no effect on proliferation of HUVEC which is an important process of the healing of the stented vessel. In addition, the occurrence of ISR after PCI with implantation of drug eluting stents was significantly associated with low vaspin plasma levels before intervention. Determination of vaspin plasma levels before PCI might be helpful in the identification of patients with high risk for development of ISR after stent implantation. In addition, the selective effects of vaspin on smooth muscle cell migration could potentially be used to reduce ISR without inhibition of re-endothelialization of the stented segment.


Assuntos
Adipocinas/fisiologia , Reestenose Coronária/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Serpinas/fisiologia , Adipocinas/sangue , Adipocinas/farmacologia , Idoso , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/patologia , Reestenose Coronária/fisiopatologia , Vasos Coronários/patologia , Vasos Coronários/fisiopatologia , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Miócitos de Músculo Liso/fisiologia , Serpinas/sangue , Serpinas/farmacologia
10.
Expert Opin Pharmacother ; 21(11): 1367-1376, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32401066

RESUMO

INTRODUCTION: Cardiac allograft vasculopathy (CAV) is a major limitation to long-term survival after heart transplantation. Its peculiar pathophysiology involves multifactorial pathways including immune-mediated and metabolic risk factors, which are associated with the development of specific pathological lesions. The often diffuse and chronic nature of the disease reduces the effectiveness of revascularization procedures, and pharmacological prevention of the disease is the sole therapeutic approach with some proven efficacy. AREAS COVERED: In this article, after briefly outlining the risk factors for CAV, the authors revise the potential pharmacological approaches that may reduce the burden of CAV. While several therapies have shown convincing efficacy in terms of CAV prevention diagnosed by coronary imaging, very few have been reported to improve prognosis with any meaningful level of evidence. EXPERT OPINION: The authors believe that a customizable approach is necessary for clinical practice given the currently available evidence. Furthermore, it is important, in the future, to address the glaring therapeutic gap of an effective treatment against donor-specific antibodies, whose effect on endothelial injury is currently one of the major mechanisms of CAV development and for which no pharmacological treatment is currently available.


Assuntos
Aloenxertos/efeitos dos fármacos , Inibidores de Calcineurina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Transplante de Coração/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imunossupressores/uso terapêutico , Aloenxertos/irrigação sanguínea , Aloenxertos/imunologia , Aloenxertos/patologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antioxidantes/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/patologia , Humanos , Inibidores da Agregação de Plaquetas/uso terapêutico , Fatores de Risco , Resultado do Tratamento
11.
Medicine (Baltimore) ; 99(20): e20135, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443326

RESUMO

BACKGROUND: Although patients with coronary artery disease (CAD) rely increasingly upon percutaneous coronary intervention (PCI), this therapy causes subsequent the complications of myocardial injury. Acupuncture safely protects the heart from ischemic injury; however, the efficacy of acupuncture for periprocedural myocardial injury after PCI remains unclear. METHODS: Seven databases in English and Chinese including PubMed, Web of Science, Cochrane Library, Embase, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, and Wanfang Database will be searched. Randomized controlled trials (RCTs) that use acupuncture to treat PCI-related myocardial injury in patients with CAD, regardless of blinding. The crossover randomized trials will be included, but only the pre-crossover data will be analyzed to avoid carryover effects. We will exclude non-RCTs, qualitative studies, uncontrolled clinical trials, and laboratory studies. The measurement of concentration of cardiac troponin (T or I) and MB isoenzyme of creatine kinase will be used as primary outcome. Postprocedural cardiac function and the major adverse cardiac/cerebrovascular event rate will be assessed as secondary outcome. Relevant data were collected independently by 2 reviewers and the third reviewer was responsible for resolving discrepancies through discussion. The Review Manager V.5.3.3 s will be used to perform the data synthesis and subgroup analysis. DISCUSSION: This systematic review and meta-analysis would provide convincing evidence of various types of acupuncture that specifically focuses on cardioprotective effect of acupuncture on PCI-related myocardial injury. REGISTRATION: Open Science Framework (OSF) registries (osf.io/n2e6t) with the registration DOI: 10.17605/OSF.IO/79H2E.


Assuntos
Terapia por Acupuntura/métodos , Doença da Artéria Coronariana/terapia , Isquemia Miocárdica/terapia , Intervenção Coronária Percutânea/efeitos adversos , Terapia por Acupuntura/estatística & dados numéricos , Cardiotônicos/farmacologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/patologia , Creatina Quinase Forma MB/sangue , Humanos , Isquemia Miocárdica/sangue , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/prevenção & controle , Intervenção Coronária Percutânea/métodos , Período Perioperatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Sensibilidade e Especificidade , Troponina/sangue
12.
Gene ; 753: 144806, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32461018

RESUMO

BACKGROUND: The aim of the present study was to detect potential gender-specific associations between some common CD36 single nucleotide polymorphisms (SNPs) and the lipid profile, as well as the susceptibility to premature multi-vessel coronary artery heart disease (CHD) in the Han population of Northern China. METHODS: A systematic three-step study process was employed to detect associations between CD36 gene variants and blood lipid profiles, as well as premature multi-vessel CHD in a gender-specific manner. RESULTS: The current study documented the following novel findings: (I) the full population-based association study in 329 Northern Han Chinese showed that four common CD36 polymorphisms were significantly related to extreme lipid profiles, with statistically significant effects based on gender interactions (rs1049673: P = 0.001; rs7755: P = 0.008; rs3211956: P = 0.034; and rs3173798: P = 0.004); (ii) these statistically significant effects could be decomposed into statistically significant atherogenic effects in males, but non-significant non-atherogenic effects in females; (iii) the results of logistic regression analysis indicated that current smoking status, low density lipoprotein cholesterol (LDL-C) levels, and type-2 diabetes were independent risk factors for premature multi-vessel CHD phenotype (P < 0.0001). CONCLUSIONS: Four common CD36 polymorphisms (rs1049673, rs7755, rs3211956, and rs3173798) were identified to be significantly associated with extreme lipid profiles and had statistically opposite gender-specific clinical lipid profile effects. Thus, the 3'-untranslated regions (3'-UTR) CD36 SNPs could be a novel target for metabolic abnormalities in males of the Han nationality from Northern China.


Assuntos
Antígenos CD36/genética , Doença da Artéria Coronariana/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/patologia , Estudos de Casos e Controles , China/epidemiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Grupos Étnicos/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Lipídeos/sangue , Lipídeos/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Caracteres Sexuais
13.
PLoS One ; 15(5): e0232735, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379805

RESUMO

BACKGROUND: Atherosclerosis is the primary cause of coronary artery disease (CAD). Several observational studies have examined the association of traditional CAD risk factors with the progression of coronary artery calcification (CAC). In our study we investigated the effect of 11 different genetic risk scores associated with CAD and CAD risk factors on the progression of CAC. METHODS AND RESULTS: We included 3097 participants from the Heinz Nixdorf Recall study who had available CAC measurements at baseline (CACb) and at the 5-year follow-up (CAC5y). A weighted genetic risk score for CAD and each of the CAD-associated risk factors was constructed. Multiple regression analyses were applied to i) the difference between the observed log(CAC5y+1) (log(obs)) and expected log(CAC5y+1) (log(exp)) at the 5-year follow-up following the individual's log(CACb+1) percentile for the time between scans (log(obs)-log(exp)) and ii) the 5-year CAC progression, defined as 5*(log(CAC5y+1)-log(CACb+1))/time between the scans, adjusted for age, sex, and log(CACb+1) as well as for risk factors. The median percent deviation from the expected (CAC5y+1) and the 5-year progression of (CAC+1) in our study were 0 (first quartile: Q1; third quartile: Q3: -0.32; 0.48) and 45.4% (0%; 171.0%) respectively. In the age-, sex- and log(CACb+1)-adjusted model, the per-standard deviation (SD) increase in CAD genetic risk score was associated with the percent deviation from the expected (CAC5y+1) (9.7% (95% confidence interval: 5.2%; 14.5%), p = 1.6x10-5) and the 5-year progression of CAC (7.1% (3.0%; 11.4%), p = 0.0005). The CAD genetic risk score explains an additional 0.6% of the observed phenotypic variance for "log(obs)-log(exp)" and 0.4% for 5-year progression of CAC. Additionally, the per-SD increase in the CAC genetic risk score was associated with the percent deviation from the expected (CAC5y+1) (6.2% (1.9%; 10.8%, p = 0.005)) explaining an additional 0.2% of the observed phenotypic variance. However, the per-SD increase in the CAC genetic risk score was not associated with the 5-year progression of CAC (4.4% (0.4%; 8.5%), p = 0.03) after multiple testing. Adjusting for risk factors did not change the results. None of the other genetic risk scores showed an association with the percent deviation from the expected (CAC5y+1) or with the 5-year progression of CAC. CONCLUSIONS: The association of the CAC genetic risk score and the CAD genetic risk score provides evidence that genetic determinants for CAC and CAD influence the progression of CAC.


Assuntos
Doença da Artéria Coronariana/genética , Vasos Coronários/patologia , Calcificação Vascular/genética , Idoso , Doença da Artéria Coronariana/patologia , Vasos Coronários/metabolismo , Progressão da Doença , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Calcificação Vascular/patologia
14.
Curr Cardiol Rev ; 16(3): 198-201, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392116

RESUMO

Like other adipokines, omentin-1 is secreted from visceral adipose tissue and plays a vital role in the development of chronic inflammatory diseases, including cardiovascular events. Recent studies have shown that circulating omentin-1 levels are associated with various metabolic risk factors, such as high blood pressure, increased waist circumference, dyslipidemia, and glucose intolerance. The decrease in serum omentin level is an independent predictor of Coronary Artery Disease (CAD) and is associated with the severity of this disease. Since there is no relevant review in the literature, we aimed to summarize the studies on the relationship between omentin-1 and CAD.


Assuntos
Doença da Artéria Coronariana/genética , Citocinas/genética , Lectinas/genética , Doença da Artéria Coronariana/patologia , Feminino , Proteínas Ligadas por GPI/genética , Humanos , Masculino , Fatores de Risco
15.
Medicine (Baltimore) ; 99(15): e19653, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282714

RESUMO

To investigate the correlation between uric acid (UA) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and coronary artery severity in acute coronary syndrome patients of different sexes.A total of 134 patients with acute coronary syndrome (ACS) were investigated. According to sex, there were 96 cases in male group and 38 cases in female group. According to the number of diseased vessels, the degree of coronary artery lesion was determined and divided into negative group (n = 21), single vessel lesion group (n = 43), double vessel lesion group (n = 38), and 3 vessel lesion group (n = 32).Univariate analysis showed that UA, NT-proBNP was correlated with the severity of ACS (P < .05). UA was an independent risk factor for the severity of coronary artery disease in female group (P < .05), but not in male group (P > .05). There was no significant correlation between NT-proBNP and severity of coronary artery disease in different sex (P > .05).UA was significantly correlated with the severity of coronary heart disease, especially in women, but not in men. The level of NT-proBNP was positively correlated with the severity of coronary artery, but no significant difference was found in different sexes.


Assuntos
Síndrome Coronariana Aguda/metabolismo , Doença da Artéria Coronariana/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Ácido Úrico/sangue , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Caracteres Sexuais
16.
Med Sci Monit ; 26: e923343, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32281613

RESUMO

BACKGROUND The presence of a Frank's sign ear crease is closely correlated with coronary artery disease (CAD). The SYNTAX score indicates the complexity of coronary lesions. This present investigation sought to identify the correlation between SYNTAX score and several specific ear creases. MATERIAL AND METHODS Four specific types of ear creases - crossing crease not originated from ear hole (CC-NEH), crossing crease originated from ear hole (CC-EH), vertical creases on the face side (VC-F), and vertical creases dividing earlobe and face (VC-EF) - were investigated in patients undergoing coronary angiography. A Frank's sign score system was introduced based on the 4 creases. Demographic data, clinical data, and SYNTAX score were also documented. The association between ear creases and SYNTAX score, as well as the correlation between Frank's score and SYNTAX score, were statistically analyzed. RESULTS CC-NEH had the highest positive predictive value (positive predictive value=0.439), and VC-F had the highest negative predictive value for the detection of intermediate and high SYNTAX score (negative predictive value=1.000). VC-EF and CC-NEH were associated with intermediate and high SYNTAX scores (OR=2.913-7.694, all P<0.05). Only 2.9% of patients with Frank's score=0 had intermediate or high SYNTAX scores, and 52.2% and 50.0% of patients with Frank's sign score=3 and 4 had intermediate or high SYNTAX scores, respectively. The Frank's sign score was significantly and positively correlated with SYNTAX score (r=0.457, P<0.001). CONCLUSIONS Features of specific ear creases and Frank's sign scores were associated with intermediate and high complexity of coronary lesions.


Assuntos
Doença da Artéria Coronariana/patologia , Orelha/anatomia & histologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
17.
Arterioscler Thromb Vasc Biol ; 40(6): 1587-1597, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32295419

RESUMO

OBJECTIVE: Healed plaques, signs of previous plaque destabilization, are frequently found in the coronary arteries. Healed plaques can now be diagnosed in living patients. We investigated the prevalence, angiographic, and optical coherence tomography features of healed plaques in patients with stable angina pectoris. Approach and Results: Patients with stable angina pectoris who had undergone optical coherence tomography imaging were included. Healed plaques were defined as plaques with one or more signal-rich layers of different optical density. Patients were divided into 2 groups based on layered or nonlayered phenotype at the culprit lesion. Among 163 patients, 87 (53.4%) had layered culprit plaque. Patients with layered culprit plaque had more multivessel disease (62.1% versus 44.7%, P=0.027) and more angiographically complex culprit lesions (64.4% versus 35.5%, P<0.001). Layered culprit plaques had higher prevalence of lipid plaque (83.9% versus 64.5%, P=0.004), macrophage infiltration (58.6% versus 35.5%, P=0.003), calcifications (78.2% versus 63.2%, P=0.035), and thrombus (28.7% versus 14.5%, P=0.029). Lipid index (P=0.001) and percent area stenosis (P=0.015) were greater in the layered group. The number of nonculprit plaques, evaluated using coronary angiograms, tended to be greater in patients with layered culprit plaque (4.2±2.5 versus 3.5±2.1, P=0.053). Nonculprit plaques in patients with layered culprit lesion had higher prevalence of layered pattern (P=0.002) and lipid phenotype (P=0.005). Lipid index (P=0.013) and percent area stenosis (P=0.002) were also greater in this group. CONCLUSIONS: In patients with stable angina pectoris, healed culprit plaques are common and have more features of vulnerability and advanced atherosclerosis both at culprit and nonculprit lesions.


Assuntos
Angina Estável/patologia , Placa Aterosclerótica/patologia , Idoso , Doença da Artéria Coronariana/patologia , Estenose Coronária/patologia , Trombose Coronária/patologia , Vasos Coronários/patologia , Feminino , Humanos , Lipídeos/análise , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Tomografia de Coerência Óptica , Calcificação Vascular/patologia
19.
Arterioscler Thromb Vasc Biol ; 40(7): 1705-1721, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32268790

RESUMO

OBJECTIVE: A decrease in nitric oxide, leading to vascular smooth muscle cell proliferation, is a common pathological feature of vascular proliferative diseases. Nitric oxide synthesis by eNOS (endothelial nitric oxide synthase) is precisely regulated by protein kinases including AKT1. ENH (enigma homolog protein) is a scaffolding protein for multiple protein kinases, but whether it regulates eNOS activation and vascular remodeling remains unknown. Approach and Results: ENH was upregulated in injured mouse arteries and human atherosclerotic plaques and was associated with coronary artery disease. Neointima formation in carotid arteries, induced by ligation or wire injury, was greatly decreased in endothelium-specific ENH-knockout mice. Vascular ligation reduced AKT and eNOS phosphorylation and nitric oxide production in the endothelium of control but not ENH-knockout mice. ENH was found to interact with AKT1 and its phosphatase PHLPP2 (pleckstrin homology domain and leucine-rich repeat protein phosphatase 2). AKT and eNOS activation were prolonged in VEGF (vascular endothelial growth factor)-induced ENH- or PHLPP2-deficient endothelial cells. Inhibitors of either AKT or eNOS effectively restored ligation-induced neointima formation in ENH-knockout mice. Moreover, endothelium-specific PHLPP2-knockout mice displayed reduced ligation-induced neointima formation. Finally, PHLPP2 was increased in the endothelia of human atherosclerotic plaques and blood cells from patients with coronary artery disease. CONCLUSIONS: ENH forms a complex with AKT1 and its phosphatase PHLPP2 to negatively regulate AKT1 activation in the artery endothelium. AKT1 deactivation, a decrease in nitric oxide generation, and subsequent neointima formation induced by vascular injury are mediated by ENH and PHLPP2. ENH and PHLPP2 are thus new proatherosclerotic factors that could be therapeutically targeted.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Lesões das Artérias Carótidas/enzimologia , Artéria Carótida Primitiva/enzimologia , Proteínas dos Microfilamentos/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Remodelação Vascular , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Aterosclerose/enzimologia , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Lesões das Artérias Carótidas/genética , Lesões das Artérias Carótidas/patologia , Lesões das Artérias Carótidas/fisiopatologia , Artéria Carótida Primitiva/patologia , Artéria Carótida Primitiva/fisiopatologia , Células Cultivadas , Doença da Artéria Coronariana/enzimologia , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/fisiopatologia , Modelos Animais de Doenças , Células Endoteliais da Veia Umbilical Humana/enzimologia , Humanos , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Microfilamentos/deficiência , Proteínas dos Microfilamentos/genética , Neointima , Óxido Nítrico/metabolismo , Fosfoproteínas Fosfatases/deficiência , Fosfoproteínas Fosfatases/genética , Fosforilação , Transdução de Sinais
20.
Mol Genet Genomics ; 295(3): 607-619, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32162118

RESUMO

Genome-wide association studies (GWASs) have identified hundreds of single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D) and coronary artery disease (CAD), respectively. Nevertheless, these studies were generally performed for single-trait/disease and failed to assess the pleiotropic role of the identified variants. To identify novel functional loci and the pleiotropic relationship between CAD and T2D, the targeted cFDR analysis on CpG-SNPs was performed by integrating two independent large and multi-centered GWASs with summary statistics of T2D (26,676 cases and 132,532 controls) and CAD (60,801 cases and 123,504 controls). Applying the cFDR significance threshold of 0.05, we observed a pleiotropic enrichment between T2D and CAD by incorporating pleiotropic effects into a conditional analysis framework. We identified 79 novel CpG-SNPs for T2D, 61 novel CpG-SNPs for CAD, and 18 novel pleiotropic loci for both traits. Among these novel CpG-SNPs, 33 of them were annotated as methylation quantitative trait locus (meQTL) in whole blood, and ten of them showed expression QTL (eQTL), meQTL, and metabolic QTL (metaQTL) effects simultaneously. To the best of our knowledge, we performed the first targeted cFDR analysis on CpG-SNPs, and our findings provided novel insights into the shared biological mechanisms and overlapped genetic heritability between T2D and CAD.


Assuntos
Doença da Artéria Coronariana/genética , Ilhas de CpG , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Locos de Características Quantitativas , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Redes Reguladoras de Genes , Pleiotropia Genética , Estudo de Associação Genômica Ampla , Humanos , Fenótipo , Mapas de Interação de Proteínas
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