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1.
J Atheroscler Thromb ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33455996

RESUMO

AIMS: Recent studies suggested plaque erosion with noncritical stenosis could be treated distinctly from that with critical stenosis, but their morphological features remained largely unknown. The present study aimed to investigate morphological features of eroded plaques with different lumen stenosis using optical coherence tomography (OCT). METHODS: A total of 348 ST-segment elevated myocardial infarction patients with culprit OCT-defined plaque erosion (OCT-erosion) were analyzed. Based on the severity of lumen area stenosis, all patients with OCT-erosions were divided into the following three groups: Group A (area stenosis <50%, n=50); Group B (50% ≤area stenosis <75%, n=146); Group C (area stenosis ≥ 75%, n=152). RESULTS: Compared with patients in Groups A and B, patients in Group C were older (p=0.008) and had higher prevalence of hypertension (p=0.029). Angiographic analysis showed that 72.0% of the eroded plaques in Group A were located in the left anterior descending artery, followed by 67.8% in Group B, and 53.9% in Group C (p=0.039). OCT analysis showed that Group A had the highest prevalence of fibrous plaques (p<0.001) and nearby bifurcation (p=0.036), but the lowest prevalence of lipid-rich plaques (p<0.001), macrophage accumulation (p<0.001), microvessels (p=0.009), cholesterol crystals (p<0.001), and calcification (p=0.023). Multivariable regression analysis showed fibrous plaque (odds ratio [OR]: 3.014, 95% confidence interval [CI]: 1.932-4.702, p<0.001) and nearby bifurcation (OR: 1.750, 95% CI: 1.109-2.761, p=0.016) were independently associated with OCT-erosion with an area stenosis of <75%. CONCLUSIONS: More than half of OCT-erosions presented with <75% area stenosis, having distinct morphological features from those of OCT-erosions with critical stenosis. Fibrous plaque and nearby bifurcation were independently associated with noncritically stenotic OCT-erosion, suggesting that eroded plaques might need individualized treatment.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33394362

RESUMO

PURPOSE: Anti-proliferative drugs released from drug-eluting stents delay cell coverage and vascular healing, which increases the risk of late stent thrombosis. We assessed the potential effects of systemic methotrexate (MTX) on cell coverage, vascular healing and inflammation activation in vivo and in vitro. METHODS: We applied MTX in the right common carotid artery in a rabbit stenting model to determine the impact on cell coverage and inflammation activation using a serial optical coherence tomography (OCT) analysis and elucidated the molecular mechanism of MTX in human umbilical vein endothelial cells (HUVECs). RESULTS: Low-dose MTX promoted the development of cell coverage and vascular healing, which was associated with fewer uncovered struts (%) and cross-sections with any uncovered struts (%) at 4 weeks of stenting. The MTX group also exhibited lower rates of heterogeneity, microvessels and per-strut low-signal-intensity layers, indicating neointimal instability at 12 weeks of stenting. In vitro, low-dose MTX strongly inhibited HUVEC apoptosis, promoted proliferation and inhibited inflammatory activation by targeting the phosphoinositide 3-kinase (PI3K)/AKT signalling pathway. CONCLUSION: Low-dose MTX may be a key means of promoting early cell coverage via the inhibition of the inflammatory response and stability of neointima by targeting inflammatory pathways after stent implantation.

3.
Circ J ; 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33504712

RESUMO

BACKGROUND: Smoking is an important risk factor of plaque erosion. This study aimed to investigate the predictors of plaque erosion in current and non-current smokers presenting with ST-segment elevation myocardial infarction (STEMI).Methods and Results:A total of 1,320 STEMI patients with culprit plaque rupture or plaque erosion detected by pre-intervention optical coherence tomography were divided into a current smoking group (n=715) and non-current smoking group (n=605). Plaque erosion accounted for 30.8% (220/715) of culprit lesions in the current smokers and 21.2% (128/605) in the non-current smokers. Multivariable analysis showed age <50 years, single-vessel disease and the absence of dyslipidemia were independently associated with plaque erosion rather than plaque rupture, regardless of smoking status. In current smokers, diabetes mellitus (odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.10-0.83; P=0.021) was negatively associated with plaque erosion as compared with plaque rupture. In non-current smokers, minimal lumen area (MLA, OR: 1.37; 95% CI: 1.16-1.62; P<0.001) and nearby bifurcation (OR: 3.20; 95% CI: 1.98-5.16; P<0.001) were positively related to plaque erosion, but not plaque rupture. CONCLUSIONS: In patients with STEMI, the presence of diabetes mellitus significantly increased the risk of rupture-based STEMI but may not have reduced the risk of plaque erosion-based STEMI in current smokers. Nearby bifurcation and larger MLA were associated with plaque erosion in non-current smokers.

4.
EuroIntervention ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33164894

RESUMO

AIMS: To test whether a non-stenting anti-thrombotic strategy was still effective at 4-year follow-up in patients enrolled in the EROSION study and to explore potential predictors of long-term prognosis. METHODS AND RESULTS: Out of 55 patients who completed 1-month follow-up, 52 patients finished 4-year follow-up. The median duration was 4.8 years (4.2 - 5.8 years). The majority of patients remained free from events, and all patients were free from hard endpoints (death, myocardial infarction, stroke, bypass surgery, or heart failure). Only 1 patient had gastrointestinal bleeding, and 11 patients underwent elective target lesion revascularization (TLR). Patients in the non-TLR group had more optical coherence tomography (OCT) thrombus reduction from baseline to 1 month; 95% patients in the non-TLR group versus 45% in the TLR group (p=0.001) met the primary endpoint (thrombus volume reduction >50%). Consistent with the OCT findings, angiographic results showed that the TLR group had less improvement in diameter stenosis (p=0.014) at 1 month compared with non-TLR group. CONCLUSIONS: Four-year follow-up findings reconfirmed the safety of an anti-thrombotic therapy without stenting for erosion-caused acute coronary syndrome. Patients with better response to anti-thrombotic therapy in the first month were less likely to require stent implantation during the next four years.

5.
BMC Cardiovasc Disord ; 20(1): 497, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33238890

RESUMO

BACKGROUND: Systematic investigation and analysis of cardiovascular health status (CVHS) of Chinese women is rare. This study aimed to assess CVHS and atherosclerotic cardiovascular disease (ASCVD) burden in the Chinese women physicians (CWP) and community-based non-physician cohort (NPC). METHODS: In this prospective, multicenter, observational study, CVHS using the American Heart Association (AHA) defined 7 metrics (such as smoking and fasting glucose) and ASCVD risk factors including hypertension, hyperlipidemia and type-2 diabetes were evaluated in CWP compared with NPC. RESULTS: Of 5832 CWP with a mean age of 44 ± 7 years, only 1.2% achieved the ideal CVHS and 90.1% showed at least 1 of the 7 AHA CVHS metrics at a poor level. Total CVHS score was significantly decreased and ASCVD risk burden was increased in postmenopausal subjects in CWP although ideal CVHS was not significantly influenced by menopause. Compared to 2596 NPC, fewer CWP had ≥ 2 risk factors (8% vs. 27%, P < 0.001); CWP scored significantly higher on healthy factors, a composite of total cholesterol, blood pressure, fasting glucose (P < 0.001), but, poorly on healthy behaviors (P < 0.001), specifically in the physical activity component; CWP also showed significantly higher levels of awareness and rates of treatment for hypertension and hyperlipidemia, but, not for type-2 diabetes. CONCLUSION: Chinese women's cardiovascular health is far from ideal and risk intervention is sub-optimal. Women physicians had lower ASCVD burden, scored higher in healthy factors, but, took part in less physical activity than the non-physician cohort. These results call for population-specific early and improved risk intervention.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32989612

RESUMO

Local factors of plaque rupture (e.g. lipid burden) are related to preprocedural thrombolysis in myocardial infarction (TIMI) flow grade during primary percutaneous coronary intervention (PCI). However, the pathological mechanism differs between plaque erosion and rupture. We aimed to identify the factors associated with reduced TIMI flow in plaque erosion. A total of 329 ST-segment elevation myocardial infarction (STEMI) patients with optical coherence tomography (OCT) identified plaque erosion were divided into 2 groups by preprocedural TIMI flow grade [TIMI 0-1 group (n = 219) and TIMI 2-3 group (n = 110)]. Patients in TIMI 0-1 group were older (age > 50 years, 68.5% vs. 51.8%, P = 0.003), and had more diabetes mellitus (18.3% vs. 8.2%, P = 0.015). Plaque erosion with TIMI flow 0-1 was less frequently located in the left anterior descending artery (LAD, 58.4% vs. 72.7%, P = 0.011), but more frequently located in the right coronary artery (RCA, 34.2% vs. 7.3%, P = 0.001) than those with TIMI flow 2-3. TIMI 0-1 group had more lipid plaques (53.9% vs. 41.8%, P = 0.039), macrophage accumulation (59.8% vs. 41.8%, P = 0.002), and calcification (34.2% vs. 21.8%, P = 0.020). In the multivariable analysis, age > 50 years, diabetes mellitus, RCA location, and macrophage accumulation were the independent predictors of reduced TIMI flow grade in STEMI patients with plaque erosion. Systemic factors (older age and diabetes mellitus) and local factors (RCA location and macrophage accumulation) were independently associated with reduced coronary flow in STEMI patients with plaque erosion. CLINICAL TRIAL REGISTRATION : ClinicalTrials.gov NCT03084991 May 17, 2017 (retrospectively registered).

7.
Circ Cardiovasc Interv ; 13(10): e009125, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32957793

RESUMO

BACKGROUND: Subclinical atherothrombosis and plaque healing may lead to rapid plaque progression. The histopathologic healed plaque has a layered appearance when imaged using optical coherence tomography. We assessed the frequency, predictors, distribution, and morphological characteristics of optical coherence tomography layered culprit and nonculprit plaques in patients with acute myocardial infarction. METHODS: A prospective series of 325 patients with acute myocardial infarction underwent optical coherence tomography imaging of all 3 native coronary arteries. Layered plaque phenotype had heterogeneous signal-rich layered tissue located close to the luminal surface that was clearly demarcated from the underlying plaque. RESULTS: Layered plaques were detected in 74.5% of patients with acute myocardial infarction. Patients with layered culprit plaques had more layered nonculprit plaques; and they more often had preinfarction angina, ST-segment-elevation myocardial infarction, higher low-density lipoprotein cholesterol, and absence of antiplatelet therapy. Layered plaques tended to cluster in the proximal segment of the left anterior descending artery and left circumflex artery but were more uniformly distributed in the right coronary artery. As compared with nonlayered plaques, layered plaques had greater optical coherence tomography lumen area stenosis at both culprit and nonculprit sites. The frequency of layered plaque phenotype (P=0.038) and maximum area of layered tissue (P<0.001) increased from nonculprit thin-cap fibroatheromas to nonculprit ruptures to culprit ruptures. CONCLUSIONS: Layered plaques were identified in 3-quarters of patients with acute myocardial infarction, especially in the culprit plaques of patients with ST-segment-elevation myocardial infarction. Layered plaques had a limited, focal distribution in the left anterior descending artery, and left circumflex artery but were more evenly distributed in the right coronary artery and were characterized by greater lumen narrowing at both culprit and nonculprit sites. Graphic Abstract: A graphic abstract is available for this article.

8.
Oxid Med Cell Longev ; 2020: 9173530, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733639

RESUMO

Cholesterol crystal- (CC-) induced endothelial cell inflammation and pyroptosis play an important role in the development of cardiovascular diseases, especially in atherosclerosis (AS). Increasing evidence suggests that cholesterol crystals are known to be a pivotal pathological marker of atherosclerotic plaque vulnerability. As a classical nonspecific anti-inflammatory drug, colchicine has been widely used in the treatment of acute gout. However, whether colchicine could alleviate CC-induced endothelial cell injury and the related mechanisms remains to be addressed. In this study, the protective effect of colchicine on human umbilical vein endothelial cells (HUVECs) was confirmed. Our results revealed that after cotreatment with colchicine and cholesterol crystals in endothelial cells, the uptake of cholesterol crystals was significantly decreased, the cell viability was obviously increased, and the release of lactate dehydrogenase (LDH) and the number of pyroptotic cells decreased significantly; then, the expression of NLRP3 inflammasome-related proteins and various inflammatory factors was also visibly suppressed; moreover, as a potent activator of NLRP3 inflammasome, the intracellular ROS level was clearly reduced, while mitochondrial membrane potential improved significantly. In addition, the expression levels of AMP-dependent kinase (AMPK) pathway-related proteins as well as various antioxidant enzymes were elevated notably in varying degrees. However, the above effects of colchicine were completely offset by the treatment of siRNA targeting AMPKα and Sirtuin1 (SIRT1). Therefore, we conclude that colchicine plays a crucial role in alleviating the intracellular inflammatory response and NLRP3 inflammation activation, attenuating the levels of cellular oxidative stress and pyroptosis in endothelial cells via regulating AMPK/SIRT1 signaling, which may be a concrete mechanism for the secondary prevention of cardiovascular diseases.

9.
Circ J ; 84(6): 985-993, 2020 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-32350230

RESUMO

BACKGROUND: Plaque erosion (PE) has been considered a secondary pathogenesis of ST-segment elevated myocardial infarction (STEMI) following plaque rupture (PR). Previous studies demonstrated that they had different demographic and histology characteristics and need different treatment strategy. But there are few non-invasive plasma biomarkers for distinguishing them. The present study aimed to identify non-invasive predictive biomarkers for PE and PR in patients with STEMI.Methods and Results:A total 108 patients were recruited and grouped into a PE group (n=36), a PR group (n=36), and an unstable angina pectoris (UAP) (n=36) group for analysis. A 9-plex tandem mass tag (TMT)-based proteomics was used to compare plasma protein profiles of PE, PR, and UAP. In total, 36 significant differential proteins (DPs) were identified among groups, 10 of which were screened out using bio-information analysis and validated with enzyme-linked immunosorbent assay (ELISA). The relationship of angiography and optical coherence tomography (OCT) imaging data and the 10 target DPs was analyzed statistically. Logistic regression showed elevated collagen type VI α-2 chain (COL6A2) and insulin-like growth factor 1 (IGF1), and decreased fermitin family homolog 3 (FERMT3), were positively associated with PE. Multivariate analysis indicated IGF1, FERMT3, and COL6A2 had independent predictive ability for PE. IGF1 was inversely correlated with lumen stenosis and the lipid arc of the plaque. CONCLUSIONS: IGF1, COL6A2, and FERMT3 are potential predictive biomarkers of PE in STEMI patients. And IGF1 was negatively correlated with the developing of culprit plaque.

11.
Stem Cell Res Ther ; 10(1): 404, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31862017

RESUMO

After publication of our article [1] we became aware that there were errors in Fig. 5b and Fig. 6c, namely that the immunofluorescence of EDU-positive cells of the CABLES1 transfection group in Fig. 5b (panel 2) and the cell cycle distribution of the combination group (treatment with the antimiR199a-3p and shRNA-CABLES1) in Fig. 6c (panel 3) were incorrectly presented.

12.
J Transl Med ; 17(1): 378, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730006

RESUMO

BACKGROUND: Atherosclerosis preferentially develops in regions of disturbed flow (DF). Emerging evidence indicates that yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which are both effectors of the Hippo pathway, sense different blood flow patterns and regulate atherosclerotic lesions. We previously found that methotrexate (MTX) reduces in-stent neoatherosclerosis, decreases the plaque burden, and has an effect on local fluid shear stress. Here, we investigated the atheroprotective effect of MTX under DF and the mechanisms underlying these properties. METHODS: Human umbilical vein endothelial cells (HUVECs) were subjected to biomechanical stretch using a parallel-plate flow system and treated with or without MTX at therapeutically relevant concentrations. Additionally, an extravascular device was used to induce DF in the left common carotid artery of C57BL/6 mice, followed by treatment with MTX or 0.9% saline. The artery was then assessed histopathologically after 4 weeks on a Western diet. RESULTS: We observed that MTX significantly inhibited DF-induced endothelial YAP/TAZ activation. Furthermore, it markedly decreased pro-inflammatory factor secretion and monocyte adhesion in HUVECs but had no effect on apoptosis. Mechanistically, AMPKa1 depletion attenuated these effects of MTX. Accordingly, MTX decreased DF-induced plaque formation, which was accompanied by YAP/TAZ downregulation in vivo. CONCLUSIONS: Taken together, we conclude that MTX exerts protective effects via the AMP-dependent kinase (AMPK)-YAP/TAZ pathway. These results provide a basis for the prevention and treatment of atherosclerosis via the inhibition of YAP/TAZ.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Aterosclerose/tratamento farmacológico , Hemorreologia , Metotrexato/uso terapêutico , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Adenilato Quinase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Aterosclerose/patologia , Atorvastatina/farmacologia , Núcleo Celular/metabolismo , Inativação Gênica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Metotrexato/farmacologia , Camundongos Endogâmicos C57BL , Modelos Biológicos , Fosforilação/efeitos dos fármacos , Placa Aterosclerótica/patologia
13.
Atherosclerosis ; 289: 94-100, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31487565

RESUMO

BACKGROUND AND AIMS: About 20% of patients with ST-segment elevated myocardial infarction (STEMI) are young adults. Morphological characteristics of culprit lesion in young STEMI patients have not been systematically evaluated in vivo. The present study aimed to investigate culprit lesion characteristics in young patients versus older patients using optical coherence tomography (OCT). METHODS: 1442 STEMI patients who underwent OCT examination of culprit lesion were included and divided into young group (age ≤50 years, n = 400) and older group (age >50 years, n = 1042). Clinical characteristics, angiography and OCT findings were compared between the two groups. RESULTS: Culprit lesions in STEMI patients aged ≤50 years had more plaque erosion (32.0% vs. 21.1%, p < 0.001) and larger minimal lumen area (2.3 ±â€¯1.7 mm2vs. 1.9 ±â€¯1.1 mm2, p < 0.001) than in those aged >50 years. As compared with older patients, lipid rich plaque (80.5% vs. 87.2%, p = 0.001), thin cap fibroatheroma (TCFA, 59.5% vs. 69.5%, p < 0.001), calcification (31.3% vs. 48.7%, p < 0.001), spotty calcification (25.3% vs. 36.1%, p < 0.001) and cholesterol crystals (26.3% vs. 38.4%, p < 0.001) were less frequently observed in young patients. A gradient increase in typical plaque vulnerability was observed from age ≤50 years to 50-70 years to >70 years. In multivariate regression analysis, age ≤50 years was independently associated with less frequency of plaque rupture, TCFA, spotty calcification, cholesterol crystals and smaller lumen area stenosis. CONCLUSIONS: Morphological characteristics of culprit lesion in young STEMI patients were different from those in older patients. Patients aged ≤50 years had more plaque erosion and less vulnerable plaque features.


Assuntos
Angiografia Coronária , Coração/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Tomografia de Coerência Óptica , Adulto , Idoso , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nitroglicerina/farmacologia , Estudos Prospectivos , Fatores de Risco
14.
Int Heart J ; 60(5): 1154-1160, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484855

RESUMO

In-stent neoatherosclerosis is an important problem after percutaneous coronary intervention. To explore the mechanisms and treatment of in-stent neoatherosclerosis, an animal model is needed. To avoid the disadvantages of current animal models, such as excessive use of X-rays and a high mortality rate, we attempted to develop an improved animal model. We explored a method that uses a short time interval to establish a rabbit model of in-stent neoatherosclerosis with a high survival rate and to evaluate its indicators. Sixty rabbits were divided into three equal groups: group A, the traditional method; group B, the standard intervention method; and group C, the improved method. In group C, we made two small incisions in each rabbit's neck, separated the common carotid, punctured it, and implanted a stent. The incision was then sutured. Four weeks later, we used optical coherence tomography (OCT) to scan all rabbits for neoatherosclerosis. We found no significant differences in OCT data between our new animal model and the traditional and interventional groups (P > 0.05). The technological success rate was higher in the new animal model (P < 0.001). We developed a new method to establish an animal model of neoatherosclerosis, which had similar results to the traditional and interventional methods.


Assuntos
Reestenose Coronária/diagnóstico por imagem , Estenose Coronária/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Stents/efeitos adversos , Tomografia de Coerência Óptica/métodos , Animais , Reestenose Coronária/mortalidade , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/mortalidade , Modelos Animais de Doenças , Humanos , Masculino , Neointima/diagnóstico por imagem , Neointima/patologia , Variações Dependentes do Observador , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/mortalidade , Falha de Prótese , Coelhos , Distribuição Aleatória , Fatores de Risco , Estatísticas não Paramétricas , Taxa de Sobrevida
15.
Biosci Rep ; 39(7)2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31239370

RESUMO

Background: Previous studies have found that hydrogen sulfide (H2S) has multiple functions such as anti-inflammatory, antioxidative in addition to biological effects among the various organs. Exaggerated proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMCs) is a key component of vascular remodeling. We hypothesized that endogenous bioactive molecular known to suppress endoplasmic reticulum (ER) stress signaling, like H2S, will inhibit the disruption of the ER-mitochondrial unit and prevent/reverse pulmonary arterial hypertension (PAH). Methods and results: A hypoxic model was established with PASMCs to investigate the possible role of H2S in PAH. Effects of H2S on proliferation of PASMCs were evaluated by CCK-8 and EdU assay treated with or without GYY4137 (donor of H2S). H2S significantly inhibited hypoxia-induced increase in PASMCs proliferation in a dose-dependent manner. H2S by intraperitoneal injection with rats both prevented and reversed chronic hypoxia-induced pulmonary hypertension in rats, decreasing pulmonary vascular resistance, pulmonary artery remodeling and right ventricular hypertrophy, and improving functional capacity without affecting systemic hemodynamic. Exogenous H2S suppressed ER stress indexes in vivo and in vitro, decreased activating transcription factor 6 activation, and inhibited the hypoxia-induced decrease in mitochondrial calcium and mitochondrial function.Conclusion: H2S effectively inhibits hypoxia-induced increase in cell proliferation, migration, and oxidative stress in PASMCs, and NOX-4 might be the underlying mechanism of PAH. Attenuating ER stress with exogenous H2S may be a novel therapeutic strategy in pulmonary hypertension with high translational potential.


Assuntos
Hipóxia Celular/genética , Sulfeto de Hidrogênio/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Morfolinas/farmacologia , Compostos Organotiofosforados/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Sulfeto de Hidrogênio/metabolismo , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/patologia , Hipóxia/complicações , Hipóxia/tratamento farmacológico , Hipóxia/genética , Hipóxia/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Morfolinas/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Compostos Organotiofosforados/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Ratos , Transdução de Sinais/efeitos dos fármacos
16.
EuroIntervention ; 15(9): e771-e778, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-30946013

RESUMO

AIMS: The aim of this study was to determine the prevalence and significance of plaque with a multilayered (ML) pattern in patients with acute coronary syndrome (ACS) versus stable angina pectoris (SAP) using OCT. METHODS AND RESULTS: Two hundred and four patients (144 ACS and 60 SAP) with OCT imaging of the culprit lesions before intervention were studied. ML plaques were identified by OCT as plaque with multiple layers of distinct optical signals. ML plaque was identified in 119 out of 204 (58.3%) patients. ML plaques were more frequently observed in SAP than ACS (75% vs 51.4%, p=0.001). Patients with prior myocardial infarction (MI) had a higher incidence of ML plaque compared with those without (74.4% vs 54.5%, p=0.024). ML plaque had a higher degree of luminal stenosis (p=0.006), longer lesion length (p=0.025), more complex lesion type (B2/C) (p<0.001) on angiography and non-significant larger plaque burden (p=0.07) on IVUS compared with those without an ML pattern. CONCLUSIONS: ML plaques, indicative of prior thrombosis, were frequently identified in patients with CAD, particularly more so in SAP and those with prior MI compared with ACS. The presence of an ML pattern is a marker of a greater extent and severity of CAD, suggesting a pathogenic link between plaque healing and lesion progression.


Assuntos
Síndrome Coronariana Aguda/patologia , Angina Estável/patologia , Placa Aterosclerótica/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Síndrome Coronariana Aguda/epidemiologia , Angina Estável/epidemiologia , Angiografia Coronária , Humanos , Infarto do Miocárdio , Placa Aterosclerótica/epidemiologia , Placa Aterosclerótica/patologia , Prevalência , Ultrassonografia de Intervenção
17.
Clin Sci (Lond) ; 133(7): 869-884, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30914441

RESUMO

Background: Early strut coverage after sirolimus-eluting stent (SES) implantation is associated with the activation of inflammation, but the underlying mechanisms are not completely understood. The present study aimed to identify the relationship between the anti-inflammatory cytokine interleukin (IL) 35 (IL-35) and early strut coverage in vivo and in vitro Methods: We utilized a retrospective study design to measure IL-35 levels in 68 stents from 68 patients with coronary artery disease and recorded serial optical coherence tomography (OCT) images (0 and 3 months) to assess stent endothelialization. The mechanism underlying the regulatory effects of IL-35 on macrophages and human umbilical vein endothelial cells (HUVECs) was also investigated. SESs were surgically implanted into the right common carotid arteries of 200 male New Zealand White rabbits receiving intravenous injections of IL-35 or a placebo.Results: At the 3-month OCT evaluation, complete endothelium coverage was correlated with IL-35 levels. IL-35 induced the activation of an anti-inflammatory M2-like macrophage phenotype by targeting the signal transducer and activators of transcription (STAT)1/4 signalling pathway, and IL-35-treated macrophages induced endothelial proliferation and alleviated endothelial dysfunction. IL-35-treated New Zealand White rabbits with implanted SESs showed lower percentages of cross-sections with an uncovered strut, elevated mean neointimal hyperplasia (NIH) thickness, and inhibited inflammatory responses.Conclusions: We investigated the effect of IL-35 expression on early stent endothelialization in vivo and in vitro and identified a crucial role for IL-35 in inducing the activation of an anti-inflammatory M2-like macrophage phenotype. The present study highlights a new therapeutic strategy for early stent endothelialization.


Assuntos
Proliferação de Células , Doença da Artéria Coronariana/terapia , Vasos Coronários/metabolismo , Stents Farmacológicos , Células Endoteliais/metabolismo , Interleucinas/sangue , Ativação de Macrófagos , Macrófagos/metabolismo , Intervenção Coronária Percutânea/instrumentação , Idoso , Animais , Biomarcadores/sangue , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Feminino , Humanos , Interleucinas/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Modelos Animais , Intervenção Coronária Percutânea/efeitos adversos , Coelhos , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Regulação para Cima
18.
J Clin Lipidol ; 13(2): 326-334.e2, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30665770

RESUMO

BACKGROUND: The role of high-density lipoprotein (HDL) subclasses in atherosclerotic diseases remains an open question. Previous clinical trials have attempted to explore the predictive effect of HDL subspecies on cardiovascular risk. However, no studies have assessed the connections between these subclasses and characteristics of plaque microstructure. OBJECTIVE: To investigate the relationship of HDL subclasses and coronary plaque stability assessed by optical coherence tomography (OCT). METHODS: Morphological characteristics of 160 nontarget lesions from 85 patients with coronary artery disease were assessed by OCT. HDL subclass profiles were analyzed using nondenaturing polyacrylamide gel electrophoresis. RESULTS: The plasma levels of small HDL subclass (percentage or concentration) were found to be positively associated with fibrous cap thickness (r = 0.232, P = .007; r = 0.243, P = .005) and negatively with maximum lipid arc (r = -0.240, P = .005; r = -0.252, P = .003) and lipid core length (r = -0.350, P < .001; r = -0.367, P < .001). Multivariate logistic regression analysis showed the small HDL subclass (percentage or concentration) (odds ratio [OR]: 0.457, 95% confidence interval [CI]: 0.214-0.974, P = .043; OR: 0.438, 95% CI: 0.204-0.938, P = .034) to be an independent factor in predicting OCT-detected thin-cap fibroatheroma of nontarget lesions. CONCLUSION: High levels of small HDL are associated with coronary nontarget plaque stability. Our findings suggest that the small HDL subtype might represent the atheroprotective activity of HDL.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Lipoproteínas HDL/sangue , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico por imagem , Tomografia de Coerência Óptica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
EuroIntervention ; 14(17): 1768-1775, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-30277462

RESUMO

AIMS: This study aimed to evaluate the relationship between pre-infarction angina (PIA) and in vivo culprit lesion characteristics as assessed by intravascular optical coherence tomography (OCT) in patients with a first ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: A total of 305 consecutive patients with a first STEMI who underwent OCT imaging of culprit lesions during primary percutaneous coronary intervention (PCI) were prospectively enrolled. OCT findings of the culprit plaque were compared between patients with (n=206) and without PIA (n=99). Patients with PIA showed lower rates of thin-cap fibroatheroma (TCFA) (62.6% vs. 80.8%, p=0.001) and plaque rupture (56.8% vs. 72.7%, p=0.007), smaller maximum ruptured cavity areas (1.10±1.04 mm2 vs. 1.53±1.20 mm2, p=0.002), and more severe residual luminal narrowing (p=0.015) with a higher incidence of white residual thrombus (68.4% vs. 50.0%, p=0.003) at the culprit lesions than patients without PIA. No significant differences in clinical outcomes were observed at the one-year follow-up. CONCLUSIONS: In patients with a first STEMI, PIA was significantly associated with a lower incidence of TCFA and plaque rupture, a smaller ruptured cavity area, more white residual thrombi, and more severe lumen stenosis at the culprit lesions.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Placa Aterosclerótica , Infarto do Miocárdio com Supradesnível do Segmento ST , Angiografia Coronária , Humanos , Infarto , Tomografia de Coerência Óptica
20.
Can J Cardiol ; 34(12): 1606-1612, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30527148

RESUMO

BACKGROUND: Patients with acute coronary syndrome show an inflammatory response that is known to affect platelet aggregation. We aimed to clarify the relationship between the inflammation severity and the effect of antiplatelet therapy after percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). METHODS: This retrospective, single-center study included 203 patients with STEMI who underwent primary PCI and were stratified on the basis of the antiplatelet therapy on admission (clopidogrel vs ticagrelor). Inflammation levels were defined as low, intermediate, and high, based on the tertiles of the distribution of high-specificity C-reactive protein levels pre-PCI. Platelet aggregation function during hospitalization and follow-up was quantified as residual adenosine diphosphate-induced platelet reactivity on light transmittance aggregometry. Inflammation markers were measured on admission and at 1 year post-PCI. RESULTS: At intermediate and high levels of inflammation, residual adenosine diphosphate-induced platelet aggregation was significantly higher among clopidogrel users than among ticagrelor users. In the clopidogrel group, statistically significant differences in platelet aggregation function were observed among the 3 levels of inflammation. At 1 year post-PCI, ticagrelor users had significantly lower levels of interleukin-1ß and higher levels of interleukin-35 and transforming growth factor-ß. CONCLUSION: At different inflammation levels, ticagrelor provides more potent platelet inhibition than clopidogrel, suggesting that ticagrelor might exert a more stable antiplatelet effect at higher levels of systemic inflammation. Furthermore, ticagrelor is associated with reduced indices of inflammation on follow-up after PCI, suggesting that anti-inflammatory effects might play a role in the clinical benefit observed with antiplatelet therapy, which would provide an additional rationale for using ticagrelor in patients with STEMI undergoing primary PCI.


Assuntos
Clopidogrel/uso terapêutico , Intervenção Coronária Percutânea , Agregação Plaquetária/efeitos dos fármacos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Ticagrelor/uso terapêutico , Biomarcadores/sangue , Proteína C-Reativa/análise , Feminino , Humanos , Interleucina-1beta/sangue , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Fator de Crescimento Transformador beta/sangue , Fator de Necrose Tumoral alfa/sangue
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