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1.
Ultrasonics ; 127: 106826, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36058188

RESUMO

Carotid artery atherosclerosis is a significant cause of stroke. Ultrasound imaging has been widely used in the diagnosis of atherosclerosis. Therefore, segmenting the atherosclerotic carotid plaque in an ultrasound image is an important task. Accurate plaque segmentation is helpful for the measurement of carotid plaque burden. This study proposes an automatic method for atherosclerotic plaque segmentation by using correntropy-based level sets (CLS) with learning-based initialization. We introduce the CLS model, containing the point-based local bias-field corrected image fitting method and correntropy-based distance measurement, to overcome the limitations of the ultrasound images. A supervised learning algorithm is employed to solve the automatic initialization problem of the variational methods. The proposed atherosclerotic plaque segmentation method is validated on 29 carotid ultrasound images, obtaining a Dice ratio of 90.6 ± 1.9% and an overlap index of 83.6 ± 3.2%. Moreover, by comparing the standard deviation of each evaluation index, it can be found that the proposed method is more robust for segmenting the atherosclerotic plaque. Our work shows that our proposed method can be more helpful than other variational models for measuring the carotid plaque burden.


Assuntos
Aterosclerose , Placa Aterosclerótica , Algoritmos , Aterosclerose/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Humanos , Placa Aterosclerótica/diagnóstico por imagem , Ultrassonografia/métodos
2.
J Colloid Interface Sci ; 629(Pt A): 399-408, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36088689

RESUMO

In vitro or in vivo fluorescence imaging based on quantum dots (QDs) has shown promise for the noninvasive diagnosis of atherosclerosis. However, simultaneous in vitro and in vivo imaging remains challenging due to the limitation of the current synthesis method of dual-emission QDs (dual-emitting hybrid QDs, and broad-spectrum emitting QDs). Herein, we fabricate a dual-emission (visible region and near-infrared region emission) QDs (ZAISe/ZnS) via the "bottom to up" method of a quaternary inorganic compound for the foam cells and atherosclerosis plaque imaging simultaneously without the intricate size modulation and the strict optical filter requirements. The oil-soluble ZAISe/ZnS is further encapsulated with bovine serum albumin (BSA) to realize phase transfer and ultimately possess the inflammation-targeting properties via biomimetic treatment with MMV (macrophage-derived micro-vesicle). The results first indicate that the as-constructed ZAISe/ZnS@BSA@MMV could accurately locate the foam cells and conduct long-term imaging of the atherosclerotic plaque, which provides a new strategy for the early and noninvasive diagnosis of atherosclerosis.


Assuntos
Aterosclerose , Placa Aterosclerótica , Pontos Quânticos , Humanos , Soroalbumina Bovina , Células Espumosas , Placa Aterosclerótica/diagnóstico por imagem , Compostos de Zinco , Sulfetos , Aterosclerose/diagnóstico por imagem
3.
Curr Probl Cardiol ; 48(1): 101424, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36167223

RESUMO

Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in revascularization of left main coronary artery (LMCA) disease has been evaluated in previous studies. However, there has been minimal study of the relationship between co-existing non-coronary atherosclerosis (NCA) and LMCA disease revascularization. We aim to examine this relationship. The Gulf-LM study is a retrospective analysis of unprotected LMCA revascularization cases undergoing PCI with second generation drug-eluting stent vs CABG across 14 centers within 3 Gulf countries between January 2015 and December 2019. A total of 2138 patients were included, 381 with coexisting NCA and 1757 without. Outcomes examined included major adverse cardiovascular and cerebrovascular events (MACCE), cardiac and non-cardiac death, and all bleeding. In patients with NCA, preexisting myocardial infarction and congestive heart failure were more common, with PCI being the most common revascularization strategy. A statistically significant reduction in in-hospital MACCE and all bleeding was noted in patients with NCA undergoing PCI as compared to CABG. At a median follow-up of 15 months, MACCE and major bleeding outcomes continued to favor the PCI group, though no such difference was identified between revascularization strategies in patients without NCA.In this multicenter retrospective study of patients with and without NCA who require revascularization (PCI and CABG) for unprotected LMCA disease, PCI demonstrated a better clinical outcome in MACCE both in-hospital and during the short-term follow-up in patients with NCA. However, no such difference was observed in patients without NCA.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Humanos , Stents Farmacológicos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/etiologia , Sistema de Registros , Aterosclerose/etiologia , Fatores de Risco , Estudos Multicêntricos como Assunto
4.
Rheum Dis Clin North Am ; 49(1): 151-163, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36424022

RESUMO

Immune and inflammatory mediators in autoimmune rheumatic diseases induce modification in the activity of enzymes pivotal for lipid metabolism and promote a proatherogenic serum lipid profile. However, disturbances in low- and high-density lipoprotein composition and increased lipid oxidation also occur. Therefore, lipoprotein dysfunction causes intracellular cholesterol accumulation in macrophages, smooth muscle cells, and platelets. Overall, both plaque progression and acute cardiovascular events are promoted. Single rheumatic diseases may present a particular pattern of lipid disturbances so that standard methods to evaluate cardiovascular risk may not be accurate enough. In general, antirheumatic drugs positively affect lipid metabolism in these patients.


Assuntos
Antirreumáticos , Aterosclerose , Doenças Autoimunes , Doenças Reumáticas , Humanos , Lipoproteínas , Aterosclerose/etiologia , Doenças Autoimunes/complicações , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológico
5.
Rheum Dis Clin North Am ; 49(1): 19-43, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36424025

RESUMO

Cardiovascular disease (CVD) risk is increased in most inflammatory rheumatic diseases (IRDs), reiterating the role of inflammation in the initiation and progression of atherosclerosis. An inverse association of CVD risk with body weight and lipid levels has been described in IRDs. Coronary artery calcium scores, plaque burden and characteristics, and carotid plaques on ultrasound optimize CVD risk estimate in IRDs. Biomarkers of cardiac injury, autoantibodies, lipid biomarkers, and cytokines also improve risk assessment in IRDs. Machine learning and deep learning algorithms for phenotype and image analysis hold promise to improve CVD risk stratification in IRDs.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Placa Aterosclerótica , Doenças Reumáticas , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco , Aterosclerose/etiologia , Placa Aterosclerótica/diagnóstico por imagem , Doenças Reumáticas/complicações , Biomarcadores , Lipídeos
6.
Rheum Dis Clin North Am ; 49(1): 81-96, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36424028

RESUMO

Takayasu's arteritis (TAK) and giant cell arteritis (GCA) are the 2 most common primary large vessel vasculitides (LVV). They share common vascular targets, clinical presentations, and histopathology, but target a strikingly different patient demographic. While GCA predominantly affects elderly people of northern European ancestry, TAK preferentially targets young women of Asian heritage. Cardiovascular diseases (CVD), including ischemic heart disease, cerebrovascular disease, aortic disease, and thromboses, are significantly increased in LVV. In this review, we will compare and contrast the issue of CVD in patients with TAK and GCA, with respect to prevalence, risk factors, and mechanisms of events to gain an understanding of the relative contributions of active vasculitis, vascular damage, and accelerated atherosclerosis. Controversies and possible mitigation strategies will be discussed.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Arterite de Células Gigantes , Arterite de Takayasu , Humanos , Feminino , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/terapia , Arterite de Células Gigantes/epidemiologia , Arterite de Células Gigantes/terapia , Arterite de Takayasu/epidemiologia , Arterite de Takayasu/terapia , Fatores de Risco
7.
Curr Probl Cardiol ; 48(1): 101436, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36183978

RESUMO

Based on the assessment of the long-term results of various surgical treatment strategies for patients with combined hemodynamically significant lesions of the coronary basin and internal carotid arteries, to develop a model for choosing the optimal revascularization strategy for patients with multifocal atherosclerosis. In 391 patients with combined hemodynamically significant atherosclerotic lesions of the coronary bed and internal carotid arteries, various options for reconstructive operations were performed. 1 - Staged surgery in the volume of coronary artery bypass grafting followed by carotid endarterectomy (n = 151, 38.6%); 2 - Combined coronary bypass surgery and carotid endarterectomy (n=141, 36%); 3 - Hybrid revascularization in the volume of percutaneous coronary intervention and carotidal endarterectomy (n = 28, 7.2%); 4 - Phased surgery in the volume of carotidal endarterectomyand subsequent coronary bypass surgery (n = 71, 18.2%). The study analyzed the frequency and structure of complications in the remote postoperative period (33.95±12.05 months - for of the total sample of patients). To select the optimal tactics of revascularization, the prognostic coefficients of all levels of risk factors for each tactic were evaluated and, on their basis, integral indicators characterizing a comprehensive assessment of risk factors for the corresponding surgical tactics were calculated. The developed model of personalized choice of the optimal surgical strategy, based on a comprehensive assessment of risk factors for an unfavorable outcome (clinical-demographic, coronary and cerebrovascular), makes it possible to predict the likelihood of developing unfavorable cardiovascular ones.


Assuntos
Aterosclerose , Estenose das Carótidas , Doença da Artéria Coronariana , Humanos , Estenose das Carótidas/complicações , Estenose das Carótidas/cirurgia , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/complicações , Estudos Retrospectivos , Resultado do Tratamento , Modelos Teóricos
8.
Maturitas ; 167: 53-59, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36306667

RESUMO

OBJECTIVES: Atherosclerosis has become a leading public health problem. Previous studies suggest that enhanced muscle strength and muscle-derived cytokines (myokines) are linked with atherosclerosis. However, no previous prospective study has examined the relationship between grip strength (GS) and carotid atherosclerosis (CAS) in middle-aged and older adults. We therefore designed a cohort study to investigate the association between GS and the incidence of CAS in a population aged 45 years and over. METHODS: The cohort study (n = 1258; follow-up range: 1-6 years, median: 4.0 years, age range: 45-85 years) was performed from 2013 to 2019 in Tianjin, China. CAS was measured using a carotid artery B-mode ultrasound system and defined by increased carotid intima-media thickness and plaques. GS was measured using a handheld digital dynamometer. Adjusted Cox proportional hazards regression models were used to assess the association between quartiles of GS and CAS. RESULTS: The incidence of CAS was 122 cases per 1000 person-years. In the final multivariable models, the adjusted hazard ratios (HRs) [95 % confidence interval (CI)] for CAS across quartiles of weight-adjusted GS (Q1-Q4) were as follows: 1.00 (reference), 0.82 (0.63, 1.06), 0.92 (0.71, 1.19), 0.69 (0.52, 0.91) and the HRs (95 % CI) across quartiles of GS (Q1-Q4) were as follows: 1.00 (reference), 1.06 (0.83, 1.36), 0.78 (0.59, 1.02), 0.76 (0.58, 0.995). For one unit and one standard deviation (SD) increase in weight-adjusted GS, the adjusted HRs (95 % CI) of CAS were 0.16 (0.05, 0.52) and 0.82 (0.72, 0.93), respectively. For one unit and one SD increase in GS, the adjusted HRs (95 % CI) of CAS were 0.98 (0.96, 0.995), and 0.47 (0.26, 0.83), respectively. CONCLUSIONS: Higher GS was associated with a lower incidence of carotid atherosclerosis in middle-aged and older adults. Further studies are required to clarify the causality.


Assuntos
Aterosclerose , Doenças das Artérias Carótidas , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Espessura Intima-Media Carotídea , Estudos de Coortes , Fatores de Risco , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Força da Mão , Artérias Carótidas/diagnóstico por imagem
9.
Phytomedicine ; 108: 154536, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36395561

RESUMO

BACKGROUND: Atherosclerosis (AS) is the pathological basis of multiple cardiovascular diseases. The pathogenesis of AS is closely related to the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). Nuciferine, an aporphine alkaloid from lotus leaf, has various pharmacological activities. However, the effect and mechanism of nuciferine on regulating proliferation and migration of VSMCs against AS is still unclear. PURPOSE: To elucidate the pharmacological effect and molecular mechanism of nuciferine on AS in ApoE(-/-) mice fed with High-Fat-Diet (HFD). STUDY DESIGN: HFD-fed ApoE(-/-) mice and 3% fetal bovine serum (FBS) induced mouse aortic vascular smooth muscle cells (MOVAS) were used to investigate the protective effect and mechanism of nuciferine on AS. METHODS: Oil red O staining was used to detect the atherosclerotic lesions. Western blotting and immunofluorescence were used to determine calmodulin 4 (Calm4) expression and localization. CCK-8 assay, transwell and wound-healing assays were used to measure the migration and proliferation of MOVAS cells. RESULTS: Nuciferine at 40 mg/kg significantly ameliorated the aortic lesion and vascular plaque in AS model, which was equal to the effect of the positive control drug (atorvastatin). In addition, nuciferine attenuated the migration and proliferation of VSMCs in vivo and in vitro. Importantly, nuciferine down-regulated the increase of Calm4 induced by HFD-fed in ApoE(-/-) mice or 3% FBS induced MOVAS cells. However, the inhibitory effect of nuciferine on the migration and proliferation of MOVAS cells was blocked when Calm4 was overexpressed. Furthermore, we found that nuciferine suppressed MMP12 and PI3K/Akt signaling pathway via Calm4. CONCLUSION: Our results illustrated that Calm4 promoted the proliferation and motility of MOVAS by activating MMP12/Akt signaling pathway in AS. Nuciferine has a significant anti-atherogenic effect by regulating the proliferation and migration of VSMCs through the Calm4/MMP12/AKT signaling pathway. Thus, Calm4 could potentially be a new target for AS therapy, and nuciferine could be a potential drug against AS.


Assuntos
Aporfinas , Aterosclerose , Animais , Camundongos , Apolipoproteínas E , Aporfinas/farmacologia , Aterosclerose/metabolismo , Movimento Celular , Proliferação de Células , Dieta Hiperlipídica , Metaloproteinase 12 da Matriz/metabolismo , Músculo Liso Vascular , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 286: 122017, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36323086

RESUMO

Visualizing lipid droplets (LDs) using fluorescence imaging is highly desirable for the diagnosis and treatment of atherosclerotic heart diseases. However, the imaging performance of the current commercial lipid probes is unsatisfactory. In this study, we prepared two probes (TTM and MeO-TTM) with aggregation-induced emission (AIE) properties for LD imaging with efficiency. Interestingly, TTM and MeO-TTM showed low emissions in H2O but their emissions were significantly increased in oil. Moreover, TTM and MeO-TTM showed great biocompatibility and intracellular LDs would be specifically illuminated by these probes with good resistance to photobleaching. In addition, TTM and MeO-TTM also exhibited great imaging performance in studying the spatial distribution of LDs in mouse atherosclerotic plaques. This work not only provides a simple tool for studying atherosclerosis but also hopes to enhance the development of fluorescent probes for LDs-specific imaging applications.


Assuntos
Aterosclerose , Placa Aterosclerótica , Camundongos , Animais , Gotículas Lipídicas , Corantes Fluorescentes , Placa Aterosclerótica/diagnóstico por imagem , Imagem Óptica , Aterosclerose/diagnóstico por imagem
11.
Ann Anat ; 245: 152006, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36183939

RESUMO

BACKGROUND: Cell-cell communication through extracellular vesicles (EVs) including exosomes, microvesicles and apoptotic bodies has been shown to be important in physiological homoeostasis as well as pathological processes such as atherosclerosis. However, while the cellular machinery controlling EV formation and composition has been studied during the past decade, less is known about the morphological process of their formation and release. METHODS: Using different electron microscopic approaches including transmission-, scanning-, immun-, and serial block face electron microscopy we studied the morphogenetic events of EV formation and release. We analysed the different steps of EV formation and release in cultured myocardial endothelial (MyEnd) and aortic endothelial (AoEnd) cell lines under serum starvation and under inflammatory conditions. RESULTS: We show that in a narrow time frame, the number of active cells and microvesicle (MV) producing cells increased in dependence of time spent in cultivation and additional stimulation by TNF-α. However, MV secretion was a highly heterogeneous process which couldn´t be seen in all cells cultivated under the same conditions. Release of MVs could be observed all over the cells' surface with no preferred release site. While no single specific microscopic approach applied was sufficient to provide a comprehensive analysis of EV biogenesis, we show that the limitations of one technique could be compensated by the qualities of the respective other applied techniques, thus enabling us to provide a detailed ultrastructural analysis of MV and exosome biogenesis. Surprisingly, exosome release in endothelial cells occurred via a yet undescribed process indicating that MVBs were incorporated into a novel distinct cellular compartment covered by fenestrated endothelium before exosome release. Lastly, we could show that TNF-α stimulation of AoEnd cells leads not only to the upregulation of CD44 in parental cells, but also to incorporation of CD44 into the membranes of generated MVs and exosomes. CONCLUSIONS: Taken together, our data contribute to a better understanding of biogenesis and release of EVs. We conclude that under inflammatory conditions, EVs can mediate the transfer of CD44 from endothelial cells to target cells at distant sites including vessel wall cells and this could be a mechanism by which MVs may change the and thus contribute to the development and progression of atherosclerotic lesions.


Assuntos
Aterosclerose , Exossomos , Vesículas Extracelulares , Humanos , Células Endoteliais , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo , Vesículas Extracelulares/metabolismo , Exossomos/química , Exossomos/metabolismo , Exossomos/ultraestrutura , Endotélio
12.
J Ethnopharmacol ; 301: 115749, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181983

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Atherosclerosis (AS) is a common systemic disease with increasing morbidity and mortality worldwide. Traditional Chinese medicine (TCM) with characteristics of multiple pathways and targets, presents advantages in the diagnosis and treatment of atherosclerosis. AIM OF THE STUDY: With the modernization of TCM, the active ingredients and molecular mechanisms of TCM for AS treatment have been gradually revealed. Therefore, it is necessary to examine the existing studies on TCM therapies aimed at regulating AS over the past two decades. MATERIALS AND METHODS: Using "atherosclerosis" and "Traditional Chinese medicine" as keywords, all relevant TCM literature published in the last 10 years was collected from electronic databases (such as Elsevier, Springer, PubMed, CNKI, and Web of Science), books and papers until March 2022, and the critical information was statistically analyzed. RESULTS: In this review, we highlighted extracts of 8 single herbs, a total of 41 single active ingredients, 20 TCM formulae, and 25 patented drugs, which were described with chemical structure, source, model, efficacy and potential mechanism. CONCLUSION: We summarized the cytopathological basis for the development of atherosclerosis involving vascular endothelial cells, macrophages and vascular smooth muscle cells, and categorically elaborated the medicinal TCM used for AS, all of which provide the current evidence on the better management of atherosclerosis by TCM.


Assuntos
Aterosclerose , Medicamentos de Ervas Chinesas , Humanos , Medicina Tradicional Chinesa , Células Endoteliais , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Miócitos de Músculo Liso , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química
13.
J Ethnopharmacol ; 301: 115787, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36206868

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Atherosclerosis (AS) is a common pathogenesis of cardiovascular diseases. Qingre Huoxue Decoction (QRHX) is an herbal formula used for the prevention and treatment of AS. However, the potential mechanism of QRHX is not clear. AIM OF THE STUDY: In our study, RNA sequencing combined with preclinical models were used to analyse the effect and mechanism of QRHX for the treatment of AS. MATERIALS AND METHODS: For in vivo studies, ApoE-/- mice were fed with a high-fat diet to induce AS. We measured weight, blood lipid, inflammatory cytokines, lipid deposition, plaque, and the M1/M2 macrophage. For in vitro studies, RAW264.7 were induced by lipopolysaccharides and treated with different concentrations of QRHX. We focusd on the relationship between QRHX, the NF-κB pathway, and macrophage polarisation, and performed simultaneous RNA sequencing both in vivo and in vitro. RESULTS: In vivo, QRHX decreased weight, improved blood lipid, relieved the degree of lipid deposition, reduced plaque area, decreased the levels of inflammatory cytokines (MCP-1, NLRP3, and TNFα), down-regulated the expression of iNOS, and up-regulated the expression of Arg-1. In vitro, QRHX down-regulated M1 markers, iNOS and CCR7, with lower concentrations of IL-1ß; furthermore, QRHX up-regulated M2 markers, Arg-1, CD163, Ym-1, and Fizz-1, with higher concentrations of IL-4 and IL-10. RNA sequencing of both samples in vivo and in vitro suggested that NF-κB was the target pathway of QRHX to regulate macrophage polarisation; this result was validated at the gene and protein levels. CONCLUSIONS: QRHX induced M2 polarisation, reduced an inflammatory response, and played a role in stabilising plaque by mediating the NF-κB signalling pathway.


Assuntos
Aterosclerose , Placa Aterosclerótica , Camundongos , Animais , NF-kappa B/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Aterosclerose/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Macrófagos , Lipopolissacarídeos/farmacologia , Citocinas/metabolismo , Placa Aterosclerótica/patologia
14.
Adv Exp Med Biol ; 1396: 139-156, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36454465

RESUMO

Despite successive advancement of genome editing technology with zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), the recent breakthrough in the field has been related to clustered regularly interspaced short palindromic repeats/associated proteins (CRISPR/Cas). The high efficiency and convenience of CRIPSR/Cas systems dramatically accelerate pre- and clinical experimentations of dyslipidemia and atherosclerosis. In this chapter, we review the latest state of genome editing in translational research of dyslipidemia and atherosclerosis. We highlight recent progress in therapeutic development for familial dyslipidemia by genome editing. We point to the challenges in maximizing efficacy and minimizing safety issues related to the once-and-done therapy focusing on CRISPR/Cas systems. We give an outlook on the potential gene targets prioritized by large-scale genetic studies of cardiovascular diseases and genome editing in precision medicine of dyslipidemia and atherosclerosis.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Dislipidemias , Humanos , Edição de Genes , Dislipidemias/genética , Dislipidemias/terapia , Aterosclerose/genética , Aterosclerose/terapia , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição
15.
J Intern Med ; 293(1): 48-62, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35982610

RESUMO

The prognosis in systemic lupus erythematosus (SLE) has improved due to better treatment and care, but cardiovascular disease (CVD) still remains an important clinical problem, since the risk of CVD in SLE is much higher than among controls. Atherosclerosis is the main cause of CVD in the general population, and in SLE, increased atherosclerosis, especially the prevalence of atherosclerotic plaques, has been demonstrated. Atherosclerosis is an inflammatory condition, where immunity plays an important role. Interestingly, oxidized low-density lipoprotein, defective clearance of dead cells, and inflammation, with a pro-inflammatory T-cell profile are characteristics of both atherosclerosis and SLE. In addition to atherosclerosis as an underlying cause of CVD in SLE, there are also other non-mutually exclusive mechanisms, and the most important of these are antiphospholipid antibodies (aPL) leading to the antiphospholipid antibody syndrome with both arterial and venous thrombosis. aPL can cause direct pro-inflammatory and prothrombotic effects on endothelial and other cells and also interfere with the coagulation, for example, by inhibiting annexin A5 from its antithrombotic and protective effects. Antibodies against phosphorylcholine (anti-PC) and other small lipid-related epitopes, sometimes called natural antibodies, are negatively associated with CVD and atherosclerosis in SLE. Taken together, a combination of traditional risk factors such as hypertension and dyslipidemia, and nontraditional ones, especially aPL, inflammation, and low anti-PC are implicated in the increased risk of CVD in SLE. Close monitoring of both traditional risk factors and nontraditional ones, including treatment of disease manifestations, not lest renal disease in SLE, is warranted.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Lúpus Eritematoso Sistêmico , Humanos , Doenças Cardiovasculares/complicações , Lúpus Eritematoso Sistêmico/complicações , Anticorpos Antifosfolipídeos , Fatores de Risco , Fosforilcolina , Inflamação/complicações
16.
PET Clin ; 18(1): 71-80, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36442967

RESUMO

Assessment of molecular changes by PET has introduced a new paradigm in atherosclerosis imaging, which has traditionally relied on anatomic changes visualized by conventional angiography or computed tomography. The use of 18F-fluorodeoxyglucose (FDG) to identify atherosclerotic changes in the vessel wall was first described more than 2 decades ago. Since then, PET tracers targeting macrophage activity, neoangiogenesis, smooth muscle activity, and other aspects of atherogenic changes have been proposed. The evolving roles of PET tracers including frontrunners FDG and 18F-sodium fluoride, which show arterial wall inflammation and microcalcification, respectively, are discussed.


Assuntos
Aterosclerose , Fluordesoxiglucose F18 , Humanos , Tomografia por Emissão de Pósitrons , Aterosclerose/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Inflamação
17.
J Mech Behav Biomed Mater ; 137: 105545, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36368188

RESUMO

Complex patterns of hemodynamic wall shear stress occur in regions of arterial branching and curvature. Areas within these regions can be highly susceptible to atherosclerosis. Although many studies have characterized the response of vascular endothelial cells to shear stress in a categorical manner, our study herein addresses the need of characterizing endothelial behaviors over a continuous range of shear stress conditions that reflect the extensive variations seen in the vasculature. We evaluated the response of human umbilical vein endothelial cell monolayers to orbital flow at 120, 250, and 350 revolutions per minute (RPM) for 24 and 72 h. The orbital shaker model uniquely provides a continuous range of shear stress conditions from low and multidirectional at the center of each well of a culture plate to high and unidirectional at the periphery. We found distinct patterns of endothelial nuclear area, nuclear major and minor diameters, nuclear aspect ratio, and expression of endothelial nitric oxide synthase over this range of shear conditions and relationships were fit with linear and, where appropriate, power functions. Nuclear area was particularly sensitive with increases in the low and multidirectional WSS region that incrementally decreased as WSS became higher in magnitude and more unidirectional over the radius of the cell layers. The patterns of all endothelial behaviors exhibited high correlations (positive and negative) with metrics of shear stress magnitude and directionality that have been shown to strongly associate with atherosclerosis. Our findings demonstrate the exquisite sensitivity of these endothelial behaviors to incremental changes in shear stress magnitude and directionality, and provide critical quantitation of these relationships for predicting the susceptibility of an arterial segment to diseases such as atherosclerosis, particularly within complex flow environments in the vasculature such as around bifurcations.


Assuntos
Aterosclerose , Óxido Nítrico Sintase Tipo III , Humanos , Óxido Nítrico Sintase Tipo III/metabolismo , Endotélio Vascular , Estresse Mecânico , Células Endoteliais da Veia Umbilical Humana
18.
Oxid Med Cell Longev ; 2022: 8803404, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457729

RESUMO

Energy intake and metabolic balance are the pillars of health preservation. Overnutrition causes nonspecific, persistently low inflammatory state known as metabolic inflammation. This condition contributes to the pathophysiology of various metabolic disorders, such as atherosclerosis, obesity, diabetes mellitus, and metabolic syndrome. The mitochondria maintain the balance of energy metabolism. Excessive energy stress can lead to mitochondrial dysfunction, which promotes metabolic inflammation. The inflammatory environment further impairs mitochondrial function. Accordingly, excellent organism design keeps the body metabolically healthy in the context of mitochondrial dysfunction, and moderate mitochondrial stress can have a beneficial effect. This review summarises the research progress on the multifaceted characterisation of mitochondrial dysfunction and its role in metabolic inflammation.


Assuntos
Aterosclerose , Mitocôndrias , Humanos , Inflamação , Metabolismo Energético , Homeostase
19.
Front Cell Infect Microbiol ; 12: 1044957, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457852

RESUMO

Background: Metabolic syndrome (MS) is a growing public health problem worldwide. The clinical impact of fecal microbiota transplantation (FMT) from healthy donors in MS patients is unclear, especially in southern Chinese populations. This study aimed to investigate the effect of washed microbiota transplantation (WMT) in MS patients in southern China. Methods: The clinical data of patients with different indications receiving 1-3 courses of WMT were retrospectively collected. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared, such as fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c)), high-density lipoprotein cholesterol (HDL-c), non-high-density lipoprotein (non-HDL-c), systolic blood pressure (SBP), diastolic blood pressure (DBP), etc. At the same time, comprehensive efficacy evaluation and atherosclerotic cardiovascular disease (ASCVD) grade assessment were performed on MS patients. Finally, 16S rRNA gene amplicon sequencing was performed on fecal samples of MS patients before and after transplantation. Results: A total of 237 patients were included, including 42 in the MS group and 195 in the non-MS group. For MS patients, WMT significantly improved the comprehensive efficacy of MS in short term 40.48% (p<0.001), medium term 36.00% (p=0.003), and long term 46.15% (p=0.020). Short-term significantly reduced FBG (p=0.023), TG (p=0.030), SBP (p=0.026) and BMI (p=0.031), and increased HDL-c (p=0.036). The medium term had a significant reduction in FBG (p=0.048), TC (p=0.022), LDL-c (p=0.043), non-HDL-c (p=0.024) and BMI (p=0.048). WMT had a significant short term (p=0.029) and medium term (p=0.011) ASCVD downgrading effect in the high-risk group of MS patients. WMT improved gut microbiota in MS patients. Conclusion: WMT had a significant improvement effect on MS patients and a significant downgrade effect on ASCVD risk in the high-risk group of patients with MS. WMT could restore gut microbiota homeostasis in MS patients. Therefore, the regulation of gut microbiota by WMT may provide a new clinical approach for the treatment of MS.


Assuntos
Aterosclerose , Microbioma Gastrointestinal , Síndrome Metabólica , Humanos , Síndrome Metabólica/terapia , LDL-Colesterol , RNA Ribossômico 16S/genética , Estudos Retrospectivos , China , Triglicerídeos
20.
Gen Physiol Biophys ; 41(6): 535-547, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36454114

RESUMO

This study clarified the effect of homocysteine on adventitial fibroblasts (AFs) and its relationship with angiotensin II type 1 receptor (AT1R). Hyperhomocysteinemia aggravated the plaque area and increased the expression of IL-6, MCP-1, and macrophage infiltration in the plaque and adventitia of the aorta, whereas telmisartan improved this effect. Hyperhomocysteinemia induced the occurrence of the AFs marker protein ER-TR7 in the plaque and entire layer of the aorta, whereas telmisartan improved these effects, indicating that homocysteine induced AFs migration and that AT1R mediated this process. The migration experiments of AFs also reached the same conclusion. Homocysteine increased the phosphorylation levels of PKC and ERK1/2 in the AFs and HEK293A cells transfected with the AT1R plasmid, whereas telmisartan inhibited this effect, indicating that homocysteine activated AT1R intracellular signaling pathway. Homocysteine also increased the AFs At1R expression. Conclusion, homocysteine promoted adventitial inflammation, induced AFs migration, and aggravated atherosclerosis by activating AT1R.


Assuntos
Aterosclerose , Hiper-Homocisteinemia , Humanos , Túnica Adventícia , Homocisteína , Receptor Tipo 1 de Angiotensina , Telmisartan , Fibroblastos
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