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1.
Yakugaku Zasshi ; 142(5): 465-471, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35491150

RESUMO

In adult diseases, chronic inflammation-related angiopathy is the main pathological condition of organ disorders such as arteriosclerosis, chronic kidney disease, and non-alcoholic steatohepatitis (NASH). Macrophages play an important role in chronic inflammation. For example, macrophage foaming is important for atherosclerosis development. In our study using Apolipoprotein E knockout mice, hyperglycemia caused by the administration of nicotinamide-streptozotocin, which is a non-obese type 2 diabetes model, promoted arteriosclerosis, while the administration of sodium glucose co-transporter 2 inhibitor markedly reduced lesions. In further studies, arteriosclerosis was ameliorated in resistin like molecule ß knockout mice, or by xanthine inhibitors. Xanthine oxidase (XO) inhibitors also improved kidney damage in a diabetic renal disorder model using KK/Ay mice and liver damage in a NASH model using high-fat, high-sucrose trans fatty acid loading. These studies suggested that atherosclerosis can be ameliorated independently of glucose and/or lipid lowering therapy, by interventions targeting macrophages. In a study using J774.1 cells, acetylated low density lipoprotein (LDL), which is a typical denatured LDL, is taken up by macrophages regardless of glucose concentrations, but very low density lipoprotein (VLDL) is taken up into cells in a glucose-dependent manner. The glucose concentration-dependent uptake of VLDL was suppressed by XO inhibitors. In addition, the overexpression of XO increased the VLDL uptake and the VLDLR expression was also increased. The glucose and nucleic acid metabolism, which are associated with its metabolism, are involved in the uptake of VLDL. In conclusion, it was strongly suggested that macrophages regulate inflammation and intracellular lipids depending on metabolism and that they may be involved in angiopathy in adult diseases.


Assuntos
Aterosclerose , Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Aterosclerose/etiologia , Glucose , Inflamação , Lipoproteínas VLDL/metabolismo , Camundongos , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/etiologia
2.
J Nutr Sci Vitaminol (Tokyo) ; 68(2): 87-96, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35491209

RESUMO

Atherosclerosis is a chronic inflammatory disease that leads to tissue ischemia. As the biologically active form of folic acid, L-5-methyltetrahydrofolate (L-5-MTHF) can improve endothelial function. And Seal oil plays a beneficial role in the progression of atherosclerosis. The study aims to evaluate beneficial effects of L-5-MTHF alone or in combination with Seal oil on atherosclerosis. Seventy-two male Wistar rats were randomly divided into 6 groups: control (normal diet), atherosclerosis (high-fat diet), folic acid (high-fat+3 mg/kg folic acid), low-dose L-5-MTHF (high-fat+3 mg/kg L-5-MTHF), low-dose L-5-MTHF+Seal oil (high-fat+3 mg/kg L-5-MTHF+0.5 g/kg Seal oil), high-dose L-5-MTHF (high-fat+10 mg/kg L-5-MTHF). After 13 wk, rats were sacrificed. Rats exhibiting atherosclerosis had dyslipidemia and serious aortic lesions. Supplementation with low-dose L-5-MTHF+Seal oil or use of high-dose L-5-MTHF increased serum folate concentrations, decreased homocysteine levels, improved the serum lipid profile, up-regulated expression of NO and NOS, enhancement of the antioxidant properties of GSH-Px activity and reduction in the concentration of MDA, levels of Olr1 and RelA mRNA decreased in aortic tissues, and expression of inflammatory factors, TNF-α, IL-6, IL-1ß and endothelial cell injury factors ET-1 and sICAM-1, were also down-regulated. In addition, HD-L-5-MTHF increased the antioxidant activity of serum SOD. We conclude that L-5-MTHF has obvious anti-inflammatory and antioxidant effects on diseased blood vessels. The intervention of L-5-MTHF alone or in combination with Seal oil can improve atherosclerosis in rats and reduce the occurrence of aortic lesions. The anti-atherosclerotic mechanism may be related to down-regulation of Olr1 and RelA expression.


Assuntos
Aterosclerose , Tetra-Hidrofolatos , Animais , Antioxidantes/farmacologia , Aterosclerose/tratamento farmacológico , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Ácido Fólico/farmacologia , Masculino , Ratos , Ratos Wistar
3.
Adv Gerontol ; 35(1): 34-43, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35522107

RESUMO

Cardiovascular diseases, including atheroscleroscoronary and cerebral arteries, are an important medical and social problem of the population, especially among the elderly and seniors. The proportion of older persons is about 80% among deaths from complications of atherosclerosis and over 60% among all detected cases of myocardial infarction in the Russian Federation. Age changes in the body negatively affect the course of the disease. Analysis of the scientific literature found age-related morphofunctional metamorphoses of the vascular wall, blood forms, lipid and carbohydrate metabolism, immune system, redox balance, microbiota. These changes exacerbate atherogenesis, as atherosclerosis is found to be a multi-factor disease with a wide range of causal relationships. Research demonstrates the possibility of developing measures that can affect different pathogenetic links of the disease. A study of transendothelial transport of lipoproteins, the role of different macrophage populations on the course of atherosclerosis, seems promising. Preventive measures aimed at preventing, early detection of both atherosclerosis itself and its complications, as well as expanding the spectrum of targeted therapy, can significantly improve the quality of life of the older generation.


Assuntos
Aterosclerose , Infarto do Miocárdio , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Metabolismo dos Carboidratos , Humanos , Infarto do Miocárdio/complicações , Qualidade de Vida
4.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35443433

RESUMO

SLE patients have an increased burden of atherosclerosis leading to adverse cardiovascular events.Alterations in endothelial function, dysregulated immune system and increased oxidative stress are implicated in their development and progression. Carotid Artery Ultrasound has been recommended by the AHA/ACC to assess and follow progression of subclinical atherosclerosis & correlate with traditional /non traditional CV risk factors in SLE. To study the correlation between Carotid Intima Media Thickness, traditional/non traditional CV risk factors in SLE. MATERIAL: Hospital based descriptive, cross sectional study.Patients with Systemic Lupus Erythematosus, diagnosed by SLICC 2012 criteria, aged > 12 years, irrespective of therapy status, between April 2019 to August 2020, were recruited by consecutive sampling. Non consenting patients, individuals with preexisting cardiovascular disease, history of MACE, hypothyroidism (detected prior to diagnosis of SLE/disease onset), smokers, PLHIV,individuals with neck surgical, radiation, were excluded. OBSERVATION: 55 SLE patients were observed. No individuals were lost to follow up. Subgroup analysis was performed between SLE with Nephritis (36) and those without Nephritis (19) as presenting features. The mean age of the study subjects is 33 years with mean disease duration of 4.6 years.SLE nephritis patients had longer disease duration,younger age of disease onset & longer duration of steroid usage.The mean Systolic BP is 134+/-20mmHg, observed to be significantly higher in SLE nephritis patients. Framingham Risk scores were positively correlated with duration of SLE disease & SLEDAI 2K scores & duration of steroid therapy. The mean CIMT of the study population is 0.91mm with 10.9% plaque prevalence whereas Mean CIMT of Lupus nephritis patients is 1.02+/- 0.27mm; but no statistically significant difference in CIMT was observed between two subgroups. Carotid Intima Media thickness was positively correlated in bivariate analysis with anti DSDNA ab levels, Framingham Risk Scores,anaemia, SLE Disease activity scores, 24hr urine proteinuria,duration of steroid usage, Serum Creatinine & CRP. No correlation between CIMT and age of subjects,FPG,TG,serum homocysteine was observed. CONCLUSION: SLE patients have a high atherosclerosis burden and are at increased risk of adverse cardiovascular events. Carotid intima media thickness measurement by USG doppler is a reliable, non invasive, inexpensive tool which helps to detect subclinical atherosclerosis and plaques in SLE patients. In this study,Lupus Nephritis patients, Neuropsychiatric SLE and SLE with secondary APS, early age of lupus onset, longer disease duration with prolonged steroid therapy,significant proteinuria, higher antiDSDNA ab levels and hypocomplementemia are observed to have higher mean CIMT and plaque formation.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Doenças das Artérias Carótidas , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Adulto , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Doenças Cardiovasculares/complicações , Espessura Intima-Media Carotídea , Estudos Transversais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Proteinúria , Fatores de Risco
5.
Int J Mol Sci ; 23(7)2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35409148

RESUMO

Atherosclerosis, accompanied by inflammation and metabolic disorders, is the primary cause of clinical cardiovascular death. In recent years, unhealthy lifestyles (e.g., sedentary lifestyles) have contributed to a worldwide epidemic of atherosclerosis. Exercise is a known treatment of atherosclerosis, but the precise mechanisms are still unknown. Here, we show that 12 weeks of regular exercise training on a treadmill significantly decreased lipid accumulation and foam cell formation in ApoE-/- mice fed with a Western diet, which plays a critical role in the process of atherosclerosis. This was associated with an increase in ß-hydroxybutyric acid (BHB) levels in the serum. We provide evidence that BHB treatment in vivo or in vitro increases the protein levels of cholesterol transporters, including ABCA1, ABCG1, and SR-BI, and is capable of reducing lipid accumulation. It also ameliorated autophagy in macrophages and atherosclerosis plaques, which play an important role in the step of cholesterol efflux. Altogether, an increase in serum BHB levels after regular exercise is an important mechanism of exercise inhibiting the development of atherosclerosis. This provides a novel treatment for atherosclerotic patients who are unable to undertake regular exercise for whatever reason. They will gain a benefit from receiving additional BHB.


Assuntos
Aterosclerose , Ácido 3-Hidroxibutírico/metabolismo , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Animais , Aterosclerose/etiologia , Colesterol/metabolismo , Células Espumosas/metabolismo , Humanos , Macrófagos/metabolismo , Camundongos
6.
J Thorac Cardiovasc Surg ; 163(5): 1739-1750.e4, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35241276

RESUMO

OBJECTIVE: The study objective was to evaluate the safety and effectiveness of the second-generation, low-profile RelayPro (Terumo Aortic) thoracic endograft for the treatment of descending thoracic aortic aneurysm or penetrating atherosclerotic ulcer. METHOD: A prospective, international, nonblinded, nonrandomized, pivotal trial analyzed a primary safety end point of major adverse events at 30 days (death, myocardial infarction, stroke, renal/respiratory failure, paralysis, bowel ischemia, procedural blood loss) and a primary effectiveness end point of treatment success at 1 year (technical success, patency, absence of aneurysm rupture, type I/III endoleaks, stent fractures, reinterventions, aneurysm expansion, and migration) compared with performance goals from the previous generation Relay pivotal study. The study was conducted in 36 centers in the United States and Japan and enrolled participants between 2017 and 2019. RESULTS: The study population of 110 patients had a median (interquartile range) age of 76 (70-81) years, 69 (62.7%) were male, and 43 (39.1%) were Asian. Patients were treated for 76 fusiform aneurysms (69%), 24 saccular aneurysms (22%), and 10 penetrating atherosclerotic ulcers (9%). Most patients (82.7%) were treated with a non-bare stent configuration. Technical success was 100%. The median (interquartile range) procedure time was 91 (64-131) minutes, and the deployment time was 16 (10-25) minutes. A total of 50 patients (73.5%) in the US cohort had percutaneous access, whereas centers in Japan used only surgical cutdown. The 30-day composite major adverse events rate was 6.4% (95% upper confidence interval, 11.6%; P = .0002): 2 strokes, 2 procedural blood losses greater than 1000 mL requiring transfusion, 2 paralysis events, and 1 renal failure. Primary effectiveness was 89.2% (lower 95% confidence interval, 81.8%; P = .0185). Nine subjects experienced 11 events (1 aneurysm expansion, 6 secondary interventions, and 4 type I endoleaks). There was no loss of stent-graft patency, no rupture, no fractures, and no migration. CONCLUSIONS: The low-profile RelayPro thoracic endograft met the study primary end points and demonstrated satisfactory 30-day safety and 1-year effectiveness for the treatment of patients with aneurysms of the descending thoracic aorta or penetrating atherosclerotic ulcers. Follow-up is ongoing to evaluate longer-term outcomes and durability.


Assuntos
Aneurisma da Aorta Torácica , Aterosclerose , Implante de Prótese Vascular , Procedimentos Endovasculares , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/etiologia , Aneurisma da Aorta Torácica/cirurgia , Aterosclerose/etiologia , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Endoleak/etiologia , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Paralisia/etiologia , Paralisia/cirurgia , Estudos Prospectivos , Desenho de Prótese , Stents , Resultado do Tratamento , Úlcera/diagnóstico por imagem , Úlcera/cirurgia , Estados Unidos
8.
Int J Mol Sci ; 23(5)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35269807

RESUMO

Cardiovascular complications are associated with advanced atherosclerosis. Although atherosclerosis is still regarded as an incurable disease, at least in its more advanced stages, the discovery of endothelial progenitor cells (EPCs), with their ability to replace old and injured cells and differentiate into healthy and functional mature endothelial cells, has shifted our view of atherosclerosis as an incurable disease, and merged traditional theories of atherosclerosis pathogenesis with evolving concepts of vascular biology. EPC alterations are involved in the pathogenesis of vascular abnormalities in atherosclerosis, but many questions remain unanswered. Many currently available drugs that impact cardiovascular morbidity and mortality have shown a positive effect on EPC biology. This review examines the role of endothelial progenitor cells in atherosclerosis development, and the impact standard antilipemic drugs, including statins, fibrates, and ezetimibe, as well as more novel treatments such as proprotein convertase subtilisin/kexin type 9 (PCSK9) modulating agents and angiopoietin-like proteins (Angtpl3) inhibitors have on EPC biology.


Assuntos
Anticolesterolemiantes , Aterosclerose , Células Progenitoras Endoteliais , Aterosclerose/tratamento farmacológico , Aterosclerose/etiologia , Aterosclerose/metabolismo , Células Progenitoras Endoteliais/metabolismo , Ezetimiba , Humanos , Pró-Proteína Convertase 9/metabolismo
9.
Endocrine ; 76(2): 324-330, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35262845

RESUMO

AIMS: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the general population. However, such a role in patients with familial hypercholesterolemia (FH) is less documented. The purpose of this study was to evaluate the association between Lp(a) concentrations and ASCVD prevalence in adult patients with FH. METHODS: This was a cross-sectional study from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Patients were categorized into 3 tertiles according to Lp(a) levels. RESULTS: A total of 541 adult patients (249 males) with possible/probable/definite FH heterozygous FH (HeFH) were included (mean age 48.5 ± 15.0 years at registration, 40.8 ± 15.9 years at diagnosis). Median (interquartile range) Lp(a) concentrations in the 1st, 2nd and 3rd Lp(a) tertile were 6.4 (3.0-9.7), 22.4 (16.0-29.1) and 77.0 (55.0-102.0) mg/dL, respectively. There was no difference in lipid profile across Lp(a) tertiles. The overall prevalence of ASCVD was 9.4% in the first, 16.1% in the second and 20.6% in the third tertile (p = 0.012 among tertiles). This was also the case for premature ASCVD, with prevalence rates of 8.5, 13.4 and 19.8%, respectively (p = 0.010 among tertiles). A trend for increasing prevalence of coronary artery disease (8.3, 12.2 and 16.1%, respectively; p = 0.076 among tertiles) was also observed. No difference in the prevalence of stroke and peripheral artery disease was found across tertiles. CONCLUSIONS: Elevated Lp(a) concentrations are significantly associated with increased prevalence of ASCVD in patients with possible/probable/definite HeFH.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Hiperlipoproteinemia Tipo II , Adulto , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos Transversais , Feminino , Humanos , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/epidemiologia , Lipoproteína(a) , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
10.
Diabetes Res Clin Pract ; 186: 109857, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35351535

RESUMO

BACKGROUND: Inflammation is closely associated with atherosclerosis and plays a crucial role in the development of cardiovascular disease. Metformin sensitizes body cells to insulin, which may cause a reduction of atherogenic lipid fractions. Low neuregulin-4 (Nrg-4) levels, an adipokine, are linked to obesity, insulin resistance, impaired glucose tolerance and type 2 diabetes. OBJECTIVES: We assessed the effect of oral supplementation with metformin on glycemic control, neuregulin-4 levels and carotid intima media thickness (CIMT) as a marker for subclinical atherosclerosis in adolescents with type 1 diabetes mellitus (T1DM) and microvascular complications. METHODS: This randomized placebo-controlled trial included 80 type 1 diabetic patients with microvascular complications who were randomly divided to receive either 24 weeks of metformin 500 mg/day or matching placebo. Fasting blood glucose (FBG), HbA1c, C-reactive protein (CRP), urinary albumin creatinine ratio (UACR), lipid profile, Nrg-4 and CIMT were assessed at baseline and study end. RESULTS: Both groups were well-matched as regards baseline clinical and laboratory data (p greater than 0.05). After 24-weeks, metformin therapy for the intervention group resulted in a significant decrease of HbA1c, CRP, UACR, total cholesterol and CIMT while Nrg-4 levels were increased compared with baseline levels (p < 0.001) and with placebo group(p < 0.001). Baseline Nrg-4 levels were negatively correlated to FBG, HbA1c, total cholesterol, CRP and CIMT. Metformin was well-tolerated. CONCLUSIONS: Oral metformin supplementation once daily for 24 weeks as an adjuvant therapy to intensive insulin in pediatric T1DM was safe and effective in improving glycemic control, dyslipidemia and Nrg-4 levels; hence, it decreased inflammation, microvascular complications and subclinical atherosclerosis.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Metformina , Adolescente , Aterosclerose/tratamento farmacológico , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Glicemia , Proteína C-Reativa , Doenças Cardiovasculares/tratamento farmacológico , Espessura Intima-Media Carotídea , Criança , Colesterol , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/uso terapêutico , Inflamação/complicações , Insulina/uso terapêutico , Lipídeos , Metformina/uso terapêutico , Neurregulinas
11.
Methods Mol Biol ; 2419: 3-19, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35237955

RESUMO

Atherosclerosis is the principal cause of cardiovascular disease that continues to be a substantial drain on healthcare systems, being responsible for about 31% of all global deaths. Atherogenesis is influenced by a range of factors, including oxidative stress, inflammation, hypertension, and hyperlipidemia, and is ultimately driven by the accumulation of low-density lipoprotein cholesterol within the arterial wall of medium and large arteries. Lipoprotein accumulation stimulates the infiltration of immune cells (such as monocytes/macrophages and T-lymphocytes), some of which take up the lipoprotein, leading to the formation of lipid-laden foam cells. Foam cell death results in increased accumulation of dead cells, cellular debris and extracellular cholesterol, forming a lipid-rich necrotic core. Vascular smooth muscle cells from the arterial media also migrate into the intima layer and proliferate, taking up the available lipids to become foam cells and producing extracellular matrix proteins such as collagen and elastin. Plaque progression is characterized by the formation of a fibrous cap composed of extracellular matrix proteins and smooth muscle cells, which acts to stabilize the atherosclerotic plaque. Degradation, thinning, and subsequent rupture of the fibrous cap leads to lumen-occlusive atherothrombosis, most commonly resulting in heart attack or stroke. This chapter describes the pathogenesis of atherosclerosis, current and emerging therapies, key challenges, and future directions of research.


Assuntos
Aterosclerose , Placa Aterosclerótica , Artérias , Aterosclerose/etiologia , Aterosclerose/terapia , Células Espumosas/patologia , Humanos , Inflamação/patologia , Placa Aterosclerótica/patologia
12.
J Autoimmun ; 128: 102813, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35247655

RESUMO

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPL) (lupus anticoagulant, anticardiolipin antibodies and anti-beta2glycoprotein I (anti-ß2GPI) antibodies) and a plethora of macro- and micro-vascular manifestations, affecting predominantly young adults. Cardiovascular events are the leading causes of morbidity and mortality in APS. APL-mediated thrombo-inflammation and atherothrombosis are emerging pathogenetic mechanisms of cardiovascular disease (CVD) in APS, involving endothelial cell and monocyte activation, cytokines and adhesion molecules expression, complement and neutrophils activation, neutrophil extracellular traps formation, platelet cell activation and aggregation, and subsequent thrombin generation, in parallel with an oxidized low-density lipoprotein (oxLDL)-ß2GPI complex induced macrophage differentiation to foam cells. High risk aPL profile, especially the presence of lupus anticoagulant and triple aPL positivity (all three aPL subtypes), co-existence with Systemic Lupus Erythematosus (SLE), as well as traditional risk factors such as smoking, hypertension, hyperlipemia and obesity are associated with both subclinical atherosclerosis and cardiovascular events in APS. Increased awareness of CVD risk by the physicians and patients, regular assessment and strict control of traditional risk factors, and lifestyle modifications are recommended. Use of low-dose aspirin should be considered for cardiovascular prevention in asymptomatic aPL carriers or SLE patients with high-risk aPL profile. The role of older agents such as hydroxychloroquine and statins or new potential targeted treatments against immuno- and athero-thrombosis has been demonstrated by experimental and some clinical studies and needs to be further evaluated by randomized controlled studies. This review summarizes the available evidence about the pathogenetic mechanisms and prevalence of cardiovascular events and subclinical atherosclerosis, the interrelationship between traditional and disease-related CVD risk factors, and the cardiovascular risk assessment and management in APS.


Assuntos
Síndrome Antifosfolipídica , Aterosclerose , Doenças Cardiovasculares , Lúpus Eritematoso Sistêmico , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Humanos , Inflamação/complicações , Inibidor de Coagulação do Lúpus , Adulto Jovem , beta 2-Glicoproteína I
13.
Oxid Med Cell Longev ; 2022: 4121173, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35300174

RESUMO

With the development of the times, cardiovascular diseases have become the biggest cause of death in the global aging society, causing a serious social burden. Atherosclerosis is a chronic inflammatory disease, which can occur in large and medium-sized blood vessels in the whole body. It takes atherosclerotic plaque as the typical pathological change and endothelial injury as the core pathophysiological mechanism. It is the pathological basis of coronary heart disease, peripheral artery disease, cerebrovascular disease, and other diseases. Recent studies have shown that chronic stress plays an important role in the occurrence and development of atherosclerosis, endothelial injury, lipid metabolism, and chronic inflammation. This process involves a large number of molecular targets. It is usually the cause of atherosclerotic cardiovascular and cerebrovascular diseases. If chronic stress factors exist for a long time, patients have genetic susceptibility, and the combination of environmental factors triggers the pathogenesis, which may eventually lead to complete blockage of the blood vessels, unstable rupture of plaques, and serious adverse cardiovascular events. This paper reviews the role of chronic stress in the occurrence and development of atherosclerosis, focusing on the pathophysiological mechanism.


Assuntos
Aterosclerose/metabolismo , Estresse Fisiológico , Animais , Aterosclerose/etiologia , Humanos
14.
Semin Immunopathol ; 44(3): 363-374, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35238952

RESUMO

Atherosclerosis is a chronic inflammatory disease of the vascular system that is characterized by the deposition of modified lipoproteins, accumulation of immune cells, and formation of fibrous tissue within the vessel wall. The disease occurs in vessels throughout the body and affects the functions of almost all organs including the lymphoid system, bone marrow, heart, brain, pancreas, adipose tissue, liver, kidneys, and gastrointestinal tract. Atherosclerosis and associated factors influence these tissues via the modulation of local vascular functions, induction of cholesterol-associated pathologies, and regulation of local immune responses. In this review, we discuss how atherosclerosis interferers with functions of different organs via several common pathways and how the disturbance of immunity in atherosclerosis can result in disease-provoking dysfunctions in multiple tissues. Our growing appreciation of the implication of atherosclerosis and associated microenvironmental conditions in the multi-organ pathology promises to influence our understanding of CVD-associated disease pathologies and to provide new therapeutic opportunities.


Assuntos
Aterosclerose , Tecido Adiposo , Aterosclerose/etiologia , Trato Gastrointestinal , Humanos , Rim , Fígado
15.
Vasc Health Risk Manag ; 18: 61-71, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35221689

RESUMO

BACKGROUND: QoL assessment within surgical treatment is seldom investigated and sparsely reported in the medical literature. This study aimed to compare QoL in a randomized fashion in the patients treated with either a laparoscopic aortobifemoral bypass (LABFB) or an open aortobifemoral bypass (OABFB) for the treatment of AIOD. PATIENTS AND METHODS: Seventy-one consecutive patients with AIOD, Trans-Atlantic Inter-Society Consensus II Type D lesions (TASC II, Type D) were randomized to LABFB or OABFB. Thirty-five patients in the LABFB and thirty-six in the OABFB groups were compared for the changes in the QoL, with the short-form health survey (SF-36), EuroQol 5 dimensions (EQ-5D), and EQ-5D visual analog scale (VAS) preoperatively, and postoperatively at 1, 3, 6, 12 and 24 months. Mann-Whitney U-Test and Wilcoxon sign-rank test were used for group comparison. Mixed model analysis was performed to examine the effect of different variables on the QoL. RESULTS: In the patients treated with LABFB, physical component score (PCS) and mental component score (MCS) in SF-36 were significantly higher than OABFB, at 1 and 3 months postoperatively. PCS was also significantly higher in the LABFB group than OABFB at 24 months postoperatively. The preoperative QoL scores for both the laparoscopy and the open group were significantly lower than the age-matched general Norwegian population. EQ-5D median scores were significantly higher in the LABFB at all postoperative follow-up time points up to 12 months. The patients in the LABFB group also had a statistically significant increase in EQ-5D VAS compared to OABFB, at 1 and 12 months postoperatively (p = 0.005, and p = 0.037, respectively). CONCLUSION: QoL seems better in patients treated with LABFB than OABFB, particularly during the early months after surgery.


Assuntos
Aterosclerose , Laparoscopia , Aterosclerose/etiologia , Inquéritos Epidemiológicos , Humanos , Laparoscopia/efeitos adversos , Medição da Dor , Qualidade de Vida , Inquéritos e Questionários
16.
Environ Res ; 209: 112803, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35120890

RESUMO

BACKGROUND: Traffic-related air pollution (TRAP) is a critical risk factor and major contributor to respiratory and cardiovascular disease (CVD). The effects of TRAP beyond the lungs can be related to changes in circulatory proteins. However, such TRAP-mediated changes have not been defined in an unbiased manner using a controlled human model. OBJECTIVE: To detail global protein changes (the proteome) in plasma following exposure to inhaled diesel exhaust (DE), a paradigm of TRAP, using controlled human exposures. METHODS: In one protocol, ex-smokers and never-smokers were exposed to filtered air (FA) and DE (300 µg PM2.5/m3), on order-randomized days, for 2 h. In a second protocol, independent never-smoking participants were exposed to lower concentrations of DE (20, 50 or 150 µg PM2.5/m3) and FA, for 4 h, on order-randomized days. Each exposure was separated by 4 weeks of washout. Plasma samples obtained 24 h post-exposure from ex-smokers (n = 6) were first probed using Slow off-rate modified aptamer proteomic array. Plasma from never-smokers (n = 11) was used for independent assessment of proteins selected from the proteomics study by immunoblotting. RESULTS: Proteomics analyses revealed that DE significantly altered 342 proteins in plasma of ex-smokers (n = 6). The top 20 proteins therein were primarily associated with inflammation and CVD. Plasma from never-smokers (n = 11) was used for independent assessment of 6 proteins, amongst the top 10 proteins increased by DE in the proteomics study, for immunoblotting. The abundance of all six proteins (fractalkine, apolipoproteins (APOB and APOM), IL18R1, MIP-3 and MMP-12) was significantly increased by DE in plasma of these never-smokers. DE-mediated increase was shown to be concentration-dependent for fractalkine, APOB and MMP-12, all biomarkers of atherosclerosis, which correlated with plasma levels of IL-6, a subclinical marker of CVD, in independent participants. CONCLUSION: This investigation details changes in the human plasma proteome due to TRAP. We identify specific atherosclerosis-related proteins that increase concentration-dependently across a range of TRAP levels applicable worldwide.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Aterosclerose , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Aterosclerose/induzido quimicamente , Aterosclerose/etiologia , Aterosclerose/metabolismo , Humanos , Proteoma , Proteômica , Distribuição Aleatória , Emissões de Veículos/análise , Emissões de Veículos/toxicidade
17.
Arterioscler Thromb Vasc Biol ; 42(3): e74-e84, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35109671

RESUMO

Clonal expansion is a process that can drive pathogenesis in human diseases, with atherosclerosis being a prominent example. Despite advances in understanding the etiology of atherosclerosis, clonality studies of vascular cells remain in an early stage. Recently, several paradigm-shifting preclinical studies have identified clonal expansion of progenitor cells in the vasculature in response to atherosclerosis. This review provides an overview of cell clonality in atherosclerotic progression, focusing particularly on smooth muscle cells and macrophages. We discuss key findings from the latest research that give insight into the mechanisms by which clonal expansion of vascular cells contributes to disease pathology. The further probing of these mechanisms will provide innovative directions for future progress in the understanding and therapy of atherosclerosis and its associated cardiovascular diseases.


Assuntos
Aterosclerose/patologia , Miócitos de Músculo Liso/patologia , Animais , Aterosclerose/etiologia , Linhagem da Célula , Proliferação de Células , Células Clonais/patologia , Modelos Animais de Doenças , Humanos , Macrófagos/patologia , Camundongos , Camundongos Transgênicos , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/patologia , Células-Tronco/patologia
18.
J Am Coll Cardiol ; 79(6): 577-593, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35144750

RESUMO

Immune checkpoint inhibitor therapy has revolutionized the treatment of advanced malignancies in recent years. Numerous reports have detailed the myriad of possible adverse inflammatory effects of immune checkpoint therapies, including within the cardiovascular system. However, these reports have been largely limited to myocarditis. The critical role of inflammation and adaptive immunity in atherosclerosis has been well characterized in preclinical studies, and several emerging clinical studies indicate a potential role of immune checkpoint targeting therapies in the development and exacerbation of atherosclerosis. In this review, we provide an overview of the role of T-cell immunity in atherogenesis and describe the molecular effects and clinical associations of both approved and investigational immune checkpoint therapy on atherosclerosis. We also highlight the role of cholesterol metabolism in oncogenesis and discuss the implications of these associations on future treatment and monitoring of atherosclerotic cardiovascular disease in the oncologic population receiving immune checkpoint therapy.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Aterosclerose/etiologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/tratamento farmacológico , Linfócitos T/imunologia , Humanos
20.
Arterioscler Thromb Vasc Biol ; 42(3): 243-252, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35109673

RESUMO

The development of innovative single-cell technologies has allowed the high-dimensional transcriptomic and proteomic profiling of individual blood and tissue cells. Recent single-cell studies revealed a new cellular heterogeneity of atherosclerotic plaque tissue and allowed a better understanding of distinct immune functional states in the context of atherosclerosis. In this brief review, we describe how single-cell technologies have shed a new light on the cellular composition of atherosclerotic plaques, and their response to diet perturbations or genetic manipulation in mouse models of atherosclerosis. We discuss how single-cell RNA sequencing, cellular indexing of transcriptomes and epitopes by sequencing, transposase-accessible chromatin with high-throughput sequencing, and cytometry by time-of-flight platforms have empowered the identification of discrete immune, endothelial, and smooth muscle cell alterations in atherosclerosis progression and regression. Finally, we review how single-cell approaches have allowed mapping the cellular and molecular composition of human atherosclerotic plaques and the discovery of new immune alterations in plaques from patients with stroke.


Assuntos
Aterosclerose/etiologia , Análise de Célula Única/métodos , Animais , Aterosclerose/imunologia , Aterosclerose/patologia , Modelos Animais de Doenças , Progressão da Doença , Perfilação da Expressão Gênica , Humanos , Camundongos , Camundongos Transgênicos , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/imunologia , Placa Aterosclerótica/patologia , Medicina de Precisão/tendências , RNA-Seq
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