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1.
J Stroke Cerebrovasc Dis ; 30(1): 105463, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33242780

RESUMO

OBJECTIVES: There is a paucity of knowledge in the literature relating to the extent of clot burden and stroke etiology. In this study, we measured the Extracted Clot Area (ECA) retrieved during endovascular treatment (EVT) and investigated relationships with suspected etiology, administration of intravenous thrombolysis and recanalization. MATERIALS AND METHODS: As part of the multi-institutional RESTORE registry, the ECA retrieved during mechanical thrombectomy was quantified using ImageJ. The effect of stroke etiology (Large-artery atherosclerosis (LAA), Cardioembolism, Cryptogenic and other) and recombinant tissue plasminogen activator (rtPA) on ECA and recanalization outcome (mTICI) was assessed. Successful recanalization was described as mTICI 2c-3. RESULTS: A total of 550 patients who underwent EVT with any clot retrieved were included in the study. The ECA was significantly larger in the LAA group compared to all other etiologies. The average ECA size of each etiology was; LAA=109 mm2, Cardioembolic=52 mm2, Cryptogenic=47 mm2 and Other=52 mm2 (p=0.014*). LAA patients also had a significantly poorer rate of successful recanalization (mTICI 2c-3) compared to all other etiologies (p=0.003*). The administration of tPA was associated with a smaller ECA in both LAA (p=0.007*) and cardioembolic (p=0.035*) groups. CONCLUSION: The ECA of LAA clots was double the size of all other etiologies and this is associated with a lower rate of successful recanalization in LAA stroke subtype. rtPA administration prior to thrombectomy was associated with reduced ECA in LAA and CE clots.


Assuntos
Aterosclerose/terapia , Procedimentos Endovasculares , Trombectomia , Terapia Trombolítica , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Aterosclerose/fisiopatologia , Circulação Cerebrovascular , Procedimentos Endovasculares/efeitos adversos , Europa (Continente) , Humanos , /etiologia , Sistema de Registros , Medição de Risco , Fatores de Risco , Trombectomia/efeitos adversos , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
2.
Ann Vasc Surg ; 70: 528-541, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32800889

RESUMO

BACKGROUND: Shaggy aorta (SA) depicts the severe aortic surface degeneration, extremely friable, and likely to cause spontaneous peripheral and visceral embolization or during catheterization, aortic manipulation, surgery, or minimally invasive procedures. This study aims to provide the most accurate and up-to-date information on this disease. METHODS: Potentially eligible studies to be included were identified by searching the following databases: CENTRAL Library, ClinicalTrials.gov, MEDLINE, and CINAHL, using a combination of subject headings and text words to identify relevant studies: (Shaggy aorta) OR (aortic embolization) OR (aortic embolism) OR (aortic thrombus) OR (aortic plaque). From a total of 29,111 abstracts, and after applying inclusion and exclusion criteria, we considered 60 studies for inclusion in this review. RESULTS: Appropriate measurement and assessment of the aortic wall are pivotal in the modern era, in particular when percutaneous procedures are performed, as SA has been identified as an independent risk factor for spinal cord injury, mesenteric embolization, and cerebral infarction after endovascular aortic repair. Furthermore, SA increases the rate of cerebral complications during transcatheter aortic valve implantation. CONCLUSIONS: In conclusion, prompt diagnosis of SA syndrome and appropriate guidelines on the management of these conditions may help physicians to better assess the patient risk and to minimize the dreadful-related complications.


Assuntos
Doenças da Aorta , Aterosclerose , Embolia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças da Aorta/complicações , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/patologia , Doenças da Aorta/terapia , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Aterosclerose/terapia , Tomada de Decisão Clínica , Embolia/diagnóstico por imagem , Embolia/etiologia , Embolia/patologia , Embolia/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Síndrome
3.
Arterioscler Thromb Vasc Biol ; 40(9): 2002-2017, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32698685

RESUMO

Despite major advances in the primary and secondary prevention of atherosclerosis and its risk factors, atherosclerotic cardiovascular disease remains a major clinical and financial burden on individuals and health systems worldwide. In addition, neointima formation and proliferation due to mechanical trauma to the vessel wall during percutaneous coronary interventions can lead to vascular restenosis and limit the longevity and effectiveness of coronary revascularization. Long noncoding RNAs (lncRNAs) have emerged as a novel class of epigenetic regulators with critical roles in the pathogenesis of atherosclerosis and restenosis following vascular injury. Here, we provide an in-depth review of lncRNAs that regulate the development of atherosclerosis or contribute to the pathogenesis of restenosis following mechanical vascular injury. We describe the diverse array of intracellular mechanisms by which lncRNAs exert their regulatory effects. We highlight the utility and challenges of lncRNAs as biomarkers. Finally, we discuss the immense translational potential of lncRNAs and strategies for targeting them therapeutically using oligonucleotide-based therapeutics and novel gene therapy platforms.


Assuntos
Artérias/metabolismo , Aterosclerose/metabolismo , RNA Longo não Codificante/metabolismo , Lesões do Sistema Vascular/metabolismo , Animais , Artérias/patologia , Aterosclerose/genética , Aterosclerose/patologia , Aterosclerose/terapia , Constrição Patológica , Epigênese Genética , Marcadores Genéticos , Humanos , Oligonucleotídeos Antissenso/uso terapêutico , Placa Aterosclerótica , RNA Longo não Codificante/genética , RNA Longo não Codificante/uso terapêutico , Terapêutica com RNAi , Transdução de Sinais , Remodelação Vascular , Lesões do Sistema Vascular/genética , Lesões do Sistema Vascular/patologia , Lesões do Sistema Vascular/terapia
4.
Biomed Eng Online ; 19(1): 44, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522205

RESUMO

BACKGROUND: Restenosis remains a challenge in the treatment of atherosclerosis due to damage to the endothelial layer and induced proliferation of smooth muscle cells. A novel radiofrequency (RF) heating strategy was proposed to selectively ablate atherosclerosis plaque and to thermally inhibit the proliferation of smooth muscle cells while keeping the endothelial cells intact. METHODS: To realize the proposed strategy, a new radiofrequency balloon catheter, consisting of three ports, a three-channel tube, a balloon and an electrode patch, was designed. To evaluate the feasibility of this new design, a phantom experiment with thermocouples measuring temperatures with different voltages applied to the electrodes was conducted. A numerical model was established to obtain the 3D temperature distribution. The heating ability was also evaluated in ex vivo diseased artery samples. RESULTS: The experimental results showed that the highest temperature could be achieved in a distance from the surface of the balloon as designed. The temperature differences between the highest temperature at 0.78 mm and those of the surface reached 9.87 °C, 12.55 °C and 16.00 °C under applied 15 V, 17.5 V and 20 V heating, respectively. In the circumferential direction, the heating region (above 50 °C) spread from the middle of the two electrodes. The numerical results showed that the cooling effect counteracted the electrical energy deposition in the region close to the electrodes. The thermal lesion could be directed to cover the diseased media away from the catheter surface. The ex vivo heating experiment also confirmed the selective heating ability of the device. The temperature at the targeted site quickly reached the set value. The temperature of the external surface was higher than the inner wall surface temperature of the diseased artery lumen. CONCLUSION: Both the experimental and numerical results demonstrated the feasibility of the newly designed RF balloon catheter. The proposed RF microelectrodes heating together with the cooling water convection can realize the desired heating in the deeper site of the blood vessel wall while sparing the thin layer of the endothelium.


Assuntos
Angioplastia com Balão/instrumentação , Aterosclerose/terapia , Ondas de Rádio , Eletrodos , Imagens de Fantasmas , Temperatura
5.
Ann Vasc Surg ; 69: 190-196, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32554196

RESUMO

BACKGROUND: Atherosclerotic disease of the innominate artery (IA) is rare and can lead to cerebral, upper extremity, and vertebral steal symptoms. Nonocclusive lesions can be treated with endovascular interventions, often with a hybrid approach while performing a right carotid endarterectomy (RCEA). Calcified IA lesions have a high risk of embolization to bilateral cerebral hemispheres. Occlusive lesions may require treatment through a median sternotomy and bypass. The purpose of our study is to review our short-term and long-term outcomes of IA revascularization. METHODS: Our operative database was used to identify patients who underwent IA revascularization between January 1998 and December 2018. Patients who underwent innominate artery stenting (IAS), combined with RCEA and IAS as well as aortoinnominate bypass (AIB), were identified. Our primary end points were freedom from neurologic event, all-cause mortality, and need for reintervention. RESULTS: Thirty-three patients (18 females [55%]) who underwent IA revascularization were identified. Average age was 67 ± 8 years, and mean clinical follow-up was 51 ± 21 months. Most patients (30 [91%]) were on a statin and antiplatelet therapy. Twenty-one patients (64%) were symptomatic. Twelve patients (36%) were asymptomatic and underwent combined RCEA with retrograde IAS for critical right carotid stenosis and IA stenosis. Preoperative imaging included a carotid duplex and computed tomography angiography. Eighteen patients (55%) underwent RCEA + IAS, 11 patients (33%) underwent isolated IAS, and 4 patients (12%) underwent AIB. In our attempt to protect bilateral hemispheres during IAS for heavily calcified lesions, we used right common carotid artery (CCA) clamping although open exposure and left CCA embolic protection filter was placed through transfemoral approach. Patients who underwent AIB had chronic heavily calcified IA occlusions or occluded IA stents with failed endovascular interventions. Perioperative stroke rate was 3%, involving 1 patient who developed reperfusion syndrome after RCEA + IAS. Perioperative mortality was 0%. Long-term stroke rate was 0%, and long-term mortality was 15% (5 of 33) because of cardiac disease. Overall restenosis rate was 9%, involving 3 patients who required secondary interventions for IA in-stent restenosis. CONCLUSIONS: IA interventions through a hybrid approach or an open approach are safe, with acceptable perioperative stroke and mortality rates. Long-term patency of these interventions is acceptable. Bilateral cerebral embolic protection can be accomplished by clamping the right CCA through an open exposure and placing a filter in the left CCA through a transfemoral approach. Patients undergoing IAS appear to have a higher rate of restenosis compared with AIB, and therefore, close follow-up with noninvasive imaging is recommended.


Assuntos
Angioplastia com Balão , Aterosclerose/terapia , Implante de Prótese Vascular , Tronco Braquiocefálico/cirurgia , Estenose das Carótidas/terapia , Endarterectomia das Carótidas , Calcificação Vascular/terapia , Idoso , Idoso de 80 Anos ou mais , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/instrumentação , Angioplastia com Balão/mortalidade , Aterosclerose/diagnóstico por imagem , Aterosclerose/mortalidade , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Implante de Prótese Vascular/mortalidade , Tronco Braquiocefálico/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/mortalidade , Bases de Dados Factuais , Dispositivos de Proteção Embólica , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Retratamento , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/cirurgia
6.
Arch Biochem Biophys ; 689: 108453, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32524996

RESUMO

Nitric oxide (NO) deficiency and NADPH oxidase plays key roles in endothelial dysfunction and atherosclerotic plaque formation. Recent evidence demonstrates that nitrate-nitrite-NO pathway in vivo exerts beneficial effects upon the cardiovascular system. We aimed to investigate the effects of dietary nitrate on endothelial function and atherosclerosis in apolipoprotein E knockout (ApoE-/-) mice fed a high-fat diet. It was shown that dietary nitrate significantly attenuated aortic endothelial dysfunction and atherosclerosis in ApoE-/- mice. Mechanistic studies revealed that dietary nitrate significantly improved plasma nitrate/nitrite, inhibited vascular NADPH oxidase activity and oxidative stress in ApoE-/- mice, while xanthine oxidoreductase (XOR) expression and activity was enhanced in ApoE-/- mice in comparison with wide type animals. These beneficial effects of nitrate in ApoE-/- mice were abolished by PTIO (NO scavenger) and significantly prevented by febuxostat (XOR inhibitor). In the presence of nitrate, no further effect of apocynin (NADPH oxidase inhibitor) was observed, suggesting NADPH oxidase as a possible target. In vitro, NO donor significantly inhibited NADPH oxidase activity in vascular endothelial cells via the induction of heme oxygenase-1. Altogether, boosting this nitrate-nitrite-NO signaling pathway resulted in the decreases of vascular NADPH oxidase-derived oxidative stress and endothelial dysfunction, and consequently protected ApoE-/- mice against atherosclerosis. These findings may have novel nutritional implications for the preventive and therapeutic strategies against vascular endothelial dysfunction in atherosclerotic disease.


Assuntos
Aterosclerose/terapia , Endotélio Vascular/patologia , NADPH Oxidases/metabolismo , Nitratos/uso terapêutico , Animais , Apolipoproteínas E/genética , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Masculino , Camundongos , Camundongos Knockout , Nitratos/metabolismo , Nitritos/metabolismo , Estresse Oxidativo
7.
Biochem Biophys Res Commun ; 527(4): 979-984, 2020 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-32439159

RESUMO

Hepatic γ-secretase regulates low-density lipoprotein receptor (LDLR) cleavage and degradation, affecting clearance of plasma triglyceride (TG)-rich lipoproteins (TRLs). In this study, we investigated whether γ-secretase inhibition modulates risk of Western (high-fat/sucrose and high-cholesterol)-type diet (WTD)-induced hepatic steatosis, dyslipidemia and atherosclerosis. We evaluated liver and plasma lipids in WTD-fed mice with hepatocyte-specific ablation of the non-redundant γ-secretase-targeting subunit Nicastrin (L-Ncst). In parallel, we investigated the effect of liver-selective Ncst antisense oligonucleotides (ASO) on lipid metabolism and atherosclerosis in wildtype (WT) and ApoE knockout (ApoE-/-) mice fed normal chow or WTD. WTD-fed L-Ncst and Ncst ASO-treated WT mice showed reduced total cholesterol and LDL-cholesterol (LDL-C), as well as reduced hepatic lipid content as compared to Cre- and control ASO-treated WT mice. Treatment of WTD-fed ApoE-/- mice with Ncst ASO markedly lowered total and LDL cholesterol, hepatic TG and attenuated atherosclerotic lesions in the aorta, as compared to control ASO-treated mice. L-Ncst and Ncst ASO similarly showed reduced plasma glucose as compared to control mice. In conclusion, inhibition of hepatic γ-secretase reduces plasma glucose, and attenuates WTD-induced dyslipidemia, hepatic fat accumulation and atherosclerosis, suggesting potential pleiotropic application for diet-induced metabolic dysfunction.


Assuntos
Secretases da Proteína Precursora do Amiloide/genética , Aterosclerose/terapia , Dislipidemias/terapia , Fígado Gorduroso/terapia , Glicoproteínas de Membrana/genética , Oligonucleotídeos Antissenso/uso terapêutico , Animais , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/genética , Dieta Ocidental/efeitos adversos , Dislipidemias/sangue , Dislipidemias/etiologia , Dislipidemias/genética , Fígado Gorduroso/sangue , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Técnicas de Inativação de Genes , Terapia Genética , Lipídeos/análise , Lipídeos/sangue , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
8.
Sci Rep ; 10(1): 8227, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32427835

RESUMO

BACKGROUND: Neoatherosclerosis represents an accelerated manifestation of atherosclerosis in nascent neointima after stenting, associated with adverse events. We investigated whether improved reendothelialization using RGD-coated stents results in diminished vascular permeability and reduced foam cell formation compared to standard DES in atherosclerotic rabbits. METHODS AND RESULTS: Neointimal foam cell formation was induced in rabbits (n = 7). Enhanced endothelial integrity in RGD-coated stents resulted in decreased vascular permeability relative to DES, which was further confirmed by SEM and TEM. Cell culture experiments examined the effect of everolimus on endothelial integrity. Increasing concentrations of everolimus resulted in a dose-dependent decrease of endothelial cell junctions and foam cell transformation of monocytes, confirming the relevance of endothelial integrity in preventing permeability of LDL. CONCLUSION: Incomplete endothelial integrity was confirmed as a key factor of neointimal foam cell formation following stent implantation. Pro-healing stent coatings may facilitate reendothelialization and reduce the risk of neoatherosclerosis.


Assuntos
Aterosclerose/terapia , Stents , Cicatrização , Animais , Aterosclerose/patologia , Modelos Animais de Doenças , Células Espumosas/patologia , Masculino , Coelhos , Túnica Íntima/patologia
9.
Int J Mol Sci ; 21(8)2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32295055

RESUMO

Amyl nitrite was introduced in 1867 as the first molecule of a new class of agents for the treatment of angina pectoris. In the following 150 years, the nitric oxide pathway has been the subject of a number of pharmacological approaches, particularly since when this elusive mediator was identified as one of the most important modulators of vascular homeostasis beyond vasomotion, including platelet function, inflammation, and atherogenesis. While having potent antianginal and antiischemic properties, however, nitric oxide donors are also not devoid of side effects, including the induction of tolerance, and, as shown in the last decade, of oxidative stress and endothelial dysfunction. In turn, endothelial dysfunction is itself felt to be involved in all stages of atherogenesis, from the development of fatty streaks to plaque rupture and thrombosis. In the present review, we summarize the agents that act on the nitric oxide pathway, with a particular focus on their potentially beneficial antiatherosclerotic and unwanted pro-atherosclerotic effects.


Assuntos
Aterosclerose/prevenção & controle , Aterosclerose/terapia , Óxido Nítrico/uso terapêutico , Animais , Aterosclerose/etiologia , Aterosclerose/metabolismo , Endotélio Vascular/metabolismo , Humanos , Redes e Vias Metabólicas , Nicorandil/administração & dosagem , Nicorandil/química , Nicorandil/metabolismo , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/uso terapêutico
10.
Arterioscler Thromb Vasc Biol ; 40(5): 1123-1134, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32237905

RESUMO

Cardiovascular disease due to atherosclerosis is still the main cause of morbidity and mortality worldwide. This disease is a complex systemic disorder arising from a network of pathological processes within the arterial vessel wall, and, outside of the vasculature, in the hematopoietic system and organs involved in metabolism. Recent years have seen tremendous efforts in the development and validation of quantitative imaging technologies for the noninvasive evaluation of patients with atherosclerotic cardiovascular disease. Specifically, the advent of combined positron emission tomography and magnetic resonance imaging scanners has opened new exciting opportunities in cardiovascular imaging. In this review, we will describe how combined positron emission tomography/magnetic resonance imaging scanners can be leveraged to evaluate atherosclerotic cardiovascular disease at the whole-body level, with specific focus on preclinical animal models of disease, from mouse to nonhuman primates. We will broadly describe 3 major areas of application: (1) vascular imaging, for advanced atherosclerotic plaque phenotyping and evaluation of novel imaging tracers or therapeutic interventions; (2) assessment of the ischemic heart and brain; and (3) whole-body imaging of the hematopoietic system. Finally, we will provide insights on potential novel technical developments which may further increase the relevance of integrated positron emission tomography/magnetic resonance imaging in preclinical atherosclerosis studies.


Assuntos
Aterosclerose/diagnóstico por imagem , Imagem por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Imagem Corporal Total/métodos , Animais , Aterosclerose/patologia , Aterosclerose/terapia , Modelos Animais de Doenças , Desenho de Equipamento , Imagem por Ressonância Magnética/instrumentação , Camundongos , Imagem Multimodal , Tomografia por Emissão de Pósitrons/instrumentação , Valor Preditivo dos Testes , Primatas , Reprodutibilidade dos Testes , Imagem Corporal Total/instrumentação
11.
Thromb Haemost ; 120(4): 538-564, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32289858

RESUMO

Thrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.


Assuntos
Aterosclerose/imunologia , Doenças Cardiovasculares/imunologia , Endotélio Vascular/fisiologia , Inflamação/imunologia , Neutrófilos/imunologia , Tromboembolia Venosa/imunologia , Animais , Aterosclerose/diagnóstico , Aterosclerose/terapia , Coagulação Sanguínea , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/terapia , Prova Pericial , Humanos , Imunidade Inata , Trombose , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/terapia
12.
Arterioscler Thromb Vasc Biol ; 40(6): 1464-1478, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32268789

RESUMO

OBJECTIVE: Despite the current antiatherosclerotic and antithrombotic therapies, the incidence of advanced atherosclerosis-associated clinical events remains high. Whether long noncoding RNAs (lncRNAs) affect the progression of atherosclerosis and whether they are potential targets for the treatment of advanced atherosclerosis are poorly understood. Approach and Results: The progression of atherosclerotic lesions was accompanied by dynamic alterations in lncRNA expression, as revealed by RNA sequencing and quantitative polymerase chain reaction. Among the dynamically changing lncRNAs, we identified a novel lncRNA, lncRNA Associated with the Progression and Intervention of Atherosclerosis (RAPIA), that was highly expressed in advanced atherosclerotic lesions and in macrophages. Inhibition of RAPIA in vivo not only repressed the progression of atherosclerosis but also exerted atheroprotective effects similar to those of atorvastatin on advanced atherosclerotic plaques that had already formed. In vitro assays demonstrated that RAPIA promoted proliferation and reduced apoptosis of macrophages. A molecular sponge interaction between RAPIA and microRNA-183-5p was demonstrated by dual-luciferase reporter and RNA immunoprecipitation assays. Rescue assays indicated that RAPIA functioned at least in part by targeting the microRNA-183-5p/ITGB1 (integrin ß1) pathway in macrophages. In addition, the transcription factor FoxO1 (forkhead box O1) could bind to the RAPIA promoter region and facilitate the expression of RAPIA. CONCLUSIONS: The progression of atherosclerotic lesions was accompanied by dynamic changes in the expression of lncRNAs. Inhibition of the pivotal lncRNA RAPIA may be a novel preventive and therapeutic strategy for advanced atherosclerosis, especially in patients resistant or intolerant to statins.


Assuntos
Aterosclerose/terapia , Expressão Gênica , Macrófagos/metabolismo , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , Animais , Apoptose/efeitos dos fármacos , Aterosclerose/genética , Aterosclerose/prevenção & controle , Atorvastatina/farmacologia , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Proteína Forkhead Box O1/metabolismo , Humanos , Integrina beta1/metabolismo , Macrófagos/química , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , MicroRNAs/metabolismo , MicroRNAs/farmacologia , Regiões Promotoras Genéticas/fisiologia , Células RAW 264.7 , RNA Longo não Codificante/fisiologia
13.
Prog Cardiovasc Dis ; 63(3): 219-227, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32277995

RESUMO

Elevated circulating concentrations of lipoprotein(a) [Lp(a)] is strongly associated with increased risk of atherosclerotic cardiovascular disease (CVD) and degenerative aortic stenosis. This relationship was first observed in prospective observational studies, and the causal relationship was confirmed in genetic studies. Everybody should have their Lp(a) concentration measured once in their lifetime. CVD risk is elevated when Lp(a) concentrations are high i.e. > 50 mg/dL (≥100 mmol/L). Extremely high Lp(a) levels >180 mg/dL (≥430 mmol/L) are associated with CVD risk similar to that conferred by familial hypercholesterolemia. Elevated Lp(a) level was previously treated with niacin, which exerts a potent Lp(a)-lowering effect. However, niacin is currently not recommended because, despite the improvement in lipid profile, no improvements on clinical outcomes have been observed. Furthermore, niacin use has been associated with severe adverse effects. Post hoc analyses of clinical trials with proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors have shown that these drugs exert clinical benefits by lowering Lp(a), independent of their potent reduction of low-density lipoprotein cholesterol (LDL-C). It is not yet known whether PCSK9 inhibitors will be of clinical use in patients with elevated Lp(a). Apheresis is a very effective approach to Lp(a) reduction, which reduces CVD risk but is invasive and time-consuming and is thus reserved for patients with very high Lp(a) levels and progressive CVD. Studies are ongoing on the practical application of genetic approaches to therapy, including antisense oligonucleotides against apolipoprotein(a) and small interfering RNA (siRNA) technology, to reduce the synthesis of Lp(a).


Assuntos
Estenose da Valva Aórtica/sangue , Valva Aórtica/patologia , Artérias/metabolismo , Aterosclerose/sangue , Calcinose/sangue , Lipoproteína(a)/sangue , Placa Aterosclerótica , Animais , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/patologia , Estenose da Valva Aórtica/terapia , Artérias/patologia , Aterosclerose/epidemiologia , Aterosclerose/patologia , Aterosclerose/terapia , Biomarcadores/sangue , Calcinose/epidemiologia , Calcinose/patologia , Calcinose/terapia , Humanos , Lipoproteína(a)/química , Prognóstico , Fatores de Risco , Regulação para Cima
14.
Eur Respir Rev ; 29(155)2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32198215

RESUMO

Multimorbidity is increasingly common and current healthcare strategies are not always aligned to treat this complex burden of disease. COPD, type-2 diabetes mellitus (T2D) and cardiovascular disease, especially atherosclerosis, occur more frequently together than expected, even when risk factors such as smoking, obesity, inactivity and poverty are considered. This supports the possibility of unifying mechanisms that contribute to the pathogenesis or progression of each condition.Neutrophilic inflammation is causally associated with COPD, and increasingly recognised in the pathogenesis of atherosclerosis and T2D, potentially forming an aetiological link between conditions. This link might reflect an overspill of inflammation from one affected organ into the systemic circulation, exposing all organs to an increased milieu of proinflammatory cytokines. Additionally, increasing evidence supports the involvement of other processes in chronic disease pathogenesis, such as cellular senescence or changes in cellular phenotypes.This review explores the current scientific evidence for inflammation, cellular ageing and cellular processes, such as reactive oxygen species production and phenotypic changes in the pathogenesis of COPD, T2D and atherosclerosis; highlighting common mechanisms shared across these diseases. We identify emerging therapeutic approaches that target these areas, but also where more work is still required to improve our understanding of the underlying cellular biology in a multimorbid disease setting.


Assuntos
Aterosclerose/imunologia , Diabetes Mellitus Tipo 2/imunologia , Inflamação/imunologia , Neutrófilos/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Animais , Aterosclerose/epidemiologia , Aterosclerose/terapia , Senescência Celular , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Humanos , Imunossenescência , Inflamação/epidemiologia , Inflamação/terapia , Mediadores da Inflamação/metabolismo , Multimorbidade , Neutrófilos/metabolismo , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Medição de Risco , Fatores de Risco , Transdução de Sinais
15.
Nutrients ; 12(3)2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32110880

RESUMO

The importance of gut microbiota in health and disease is being highlighted by numerous research groups worldwide. Atherosclerosis, the leading cause of heart disease and stroke, is responsible for about 50% of all cardiovascular deaths. Recently, gut dysbiosis has been identified as a remarkable factor to be considered in the pathogenesis of cardiovascular diseases (CVDs). In this review, we briefly discuss how external factors such as dietary and physical activity habits influence host-microbiota and atherogenesis, the potential mechanisms of the influence of gut microbiota in host blood pressure and the alterations in the prevalence of those bacterial genera affecting vascular tone and the development of hypertension. We will also be examining the microbiota as a therapeutic target in the prevention of CVDs and the beneficial mechanisms of probiotic administration related to cardiovascular risks. All these new insights might lead to novel analysis and CVD therapeutics based on the microbiota.


Assuntos
Aterosclerose/microbiologia , Aterosclerose/patologia , Microbioma Gastrointestinal , Animais , Aterosclerose/prevenção & controle , Aterosclerose/terapia , Transplante de Microbiota Fecal , Humanos , Terapia de Alvo Molecular , Medicina de Precisão , Probióticos/uso terapêutico
16.
Arterioscler Thromb Vasc Biol ; 40(5): 1110-1122, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32131612

RESUMO

The immune system plays an important role in obesity-induced adipose tissue inflammation and the resultant metabolic dysfunction, which can lead to hypertension, dyslipidemia, and insulin resistance and their downstream sequelae of type 2 diabetes mellitus and cardiovascular disease. While macrophages are the most abundant immune cell type in adipose tissue, other immune cells are also present, such as B cells, which play important roles in regulating adipose tissue inflammation. This brief review will overview B-cell subsets, describe their localization in various adipose depots and summarize our knowledge about the function of these B-cell subsets in regulating adipose tissue inflammation, obesity-induced metabolic dysfunction and atherosclerosis.


Assuntos
Tecido Adiposo/imunologia , Aterosclerose/imunologia , Subpopulações de Linfócitos B/imunologia , Paniculite/imunologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Anti-Inflamatórios/uso terapêutico , Aterosclerose/diagnóstico , Aterosclerose/metabolismo , Aterosclerose/terapia , Autoimunidade , Subpopulações de Linfócitos B/efeitos dos fármacos , Subpopulações de Linfócitos B/metabolismo , Subpopulações de Linfócitos B/patologia , Comunicação Celular , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Imunoterapia , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Paniculite/diagnóstico , Paniculite/metabolismo , Paniculite/terapia , Fenótipo , Transdução de Sinais
17.
Front Biosci (Schol Ed) ; 12: 173-199, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32114454

RESUMO

Atherosclerosis is one of the leading causes of death from cardiovascular disease (CVD) that primarily involves  mid size and large arteries. Atherosclerosis is associated with disruption of lipid metabolism and chronic inflammatory processes. One approach for treatment of atherosclerosis is by virtue of epigenetic control by noncoding RNAs (ncRNA) including miRNA, siRNA and lncRNA,  commonly employing miRNA antagonists and mimic compounds. Here, we review such usages as well as other approaches for correcting the molecular lesions of atherosclerosis including specific activation of atheroprotective miRNAs, as well as use of siRNAs and lcRNA to control aberrant lipid metabolism.  We also discuss some of these technologies that have already shown to be effective in clinical trials and are likely to enter the clinical arena.


Assuntos
Aterosclerose/genética , Aterosclerose/terapia , Terapia Genética/métodos , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Epigênese Genética , Humanos , Metabolismo dos Lipídeos/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Interferente Pequeno/genética , RNA não Traduzido/metabolismo
18.
Expert Rev Med Devices ; 17(3): 189-200, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32101062

RESUMO

Introduction: Coronary bifurcation lesions are involved in up to 20% of all percutaneous coronary interventions (PCI). However, bifurcation lesion intervention is associated with a high complication rate, and optimal treatment of coronary bifurcation is an ongoing debate.Areas covered: Both different stenting techniques and a variety of devices have been suggested for bifurcation treatment, including the use of conventional coronary stents, bioresorbable vascular scaffolds (BVS), drug-eluting balloons (DEB), and stents dedicated to bifurcations. This review will summarize different therapeutic approaches with their advantages and shortcomings, with special emphasis on histopathologic and physiologic effects of each treatment strategy.Expert opinion: Histopathology and clinical data have shown that a more simple treatment strategy is beneficial in bifurcation lesions, achieving superior results. Bifurcation interventions through balloon angioplasty or placement of stents can importantly alter the bifurcation's geometry and accordingly modify local flow conditions. Computational fluid dynamics (CFD) studies have shown that the outcome of bifurcation interventions is governed by local hemodynamic shear conditions. Minimizing detrimental flow conditions as much as possible should be the ultimate strategy to achieve long-term success of bifurcation interventions.


Assuntos
Stents/tendências , Aterosclerose/terapia , Humanos , Tecidos Suporte/química , Resultado do Tratamento
19.
Biomed Res Int ; 2020: 3495682, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32047809

RESUMO

Atherosclerosis is an inflammatory disease characterized by lipid deposits in the subendothelial space leading to severe inflammation. Nonalcoholic fatty liver disease (NAFLD) shares several risk factors with atherosclerosis, including dyslipidemia, type 2 diabetes mellitus, and metabolic syndrome, all of which lead to lipid deposition in the liver causing inflammation and fibrosis. Several clinical trials have shown that certain Chinese herbal medicines with anti-inflammatory effects can be used as adjuvant therapy to prevent the development of cardiovascular events and liver disease. Ling Zhi 8 (LZ8) is an immunomodulatory protein isolated from a medicinal mushroom and has been well documented to possess a broad range of pharmacological properties. This study aimed to evaluate the protective effects of recombinant Lactococcus lactis expressing LZ8 protein on NAFLD and atherogenesis in a cholesterol-fed rabbit model. Twelve rabbits were divided into three groups and fed with syrup only, L. lactis vehicle, or recombinant L. lactis-LZ8 once a day on weekdays for five weeks, respectively. The gene expression of IL-1ß in the aorta was significantly suppressed after oral administration of L. lactis-LZ8. Moreover, in hematoxylin and eosin staining of the aorta, the intima-medial thickness was decreased, and foam cells were significantly reduced in the subendothelial space. LZ8 also inhibited the expression of IL-1ß in the liver, decreased fat droplet deposits and infiltration of inflammatory cells, and improved liver function by decreasing liver enzymes in an animal model. Our results suggest that the Lactococcus-expressing LZ8 appears to be a promising medicine for improving both NAFLD and early atherogenesis owing to its anti-inflammatory effect. Furthermore, it is available as a low-cost food-grade product.


Assuntos
Aterosclerose/terapia , Colesterol/efeitos adversos , Lactococcus lactis/metabolismo , Hepatopatia Gordurosa não Alcoólica/terapia , Proteínas Recombinantes/farmacologia , Administração Oral , Animais , Anti-Inflamatórios/farmacologia , Aorta/metabolismo , Aorta/patologia , Aterosclerose/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Proteínas Fúngicas/genética , Imunomodulação , Lactococcus lactis/genética , Lipídeos/sangue , Fígado/metabolismo , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Coelhos , Proteínas Recombinantes/genética
20.
J Cardiovasc Transl Res ; 13(5): 744-757, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32072564

RESUMO

The pathobiology of atherosclerosis and its current and potential future treatments are summarized, with a spotlight on three central cell types involved: (i) endothelial cells (ECs), (ii) macrophages, and (iii) vascular smooth muscle cells (VSMCs). (i) EC behaviour is regulated by the central transcription factors YAP/TAZ in reaction to biomechanical forces, such as hemodynamic shear stress. (ii) VSMC transdifferentiation (phenotype switching) to a macrophage-like phenotype contributes to the majority of cells positive for common cell surface macrophage markers in atherosclerotic plaques. (iii) Intra-plaque macrophages originate in a significant number from vascular resident macrophages. They can be activated via pattern recognition receptors on cell membrane (e.g. toll-like receptors) and inside cells (e.g. inflammasomes), requiring priming by neutrophil extracellular traps (NETs). ECs and macrophages can also be characterized by single-cell RNA sequencing. Adaptive immunity plays an important role in the inflammatory process. Future therapeutic options include vaccination, TRAF-STOPs, senolysis, or CD47 blockade. Graphical Abstract.


Assuntos
Aterosclerose/patologia , Células Endoteliais/patologia , Macrófagos/patologia , Miócitos de Músculo Liso/patologia , Imunidade Adaptativa , Animais , Aterosclerose/imunologia , Aterosclerose/metabolismo , Aterosclerose/terapia , Proliferação de Células , Transdiferenciação Celular , Células Endoteliais/imunologia , Células Endoteliais/metabolismo , Humanos , Ativação de Macrófagos , Macrófagos/imunologia , Macrófagos/metabolismo , Mecanotransdução Celular , Miócitos de Músculo Liso/imunologia , Miócitos de Músculo Liso/metabolismo , Estresse Mecânico
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