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1.
Int J Mol Sci ; 22(6)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808697

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are a group of drugs whose main mechanism of action is binding to the PCSK-9 molecule, which reduces the degradation of the low-density lipoprotein receptor (LDL-R) and, hence, increases the uptake of low-density lipoprotein cholesterol (LDLc) from the bloodstream as well as reducing its concentration. The effectiveness of three monoclonal antibodies, namely, alirocumab (human IgG1/κ monoclonal antibody, genetically engineered in Chinese hamster ovary cells), evolocumab (the first fully human monoclonal antibody), and bococizumab (humanized mouse antibody), in inhibiting the action of PCSK-9 and reducing LDLc levels has been confirmed. The first two, after clinical trials, were approved by the Food and Drug Administration (FDA) and are used primarily in the treatment of autosomal familial hypercholesterolemia and in cases of statin intolerance. They are currently used both as monotherapy and in combination with statins and ezetimibe to intensify therapy and achieve therapeutic goals following the American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines. However, the lipid-lowering effect is not the only effect of action described by researchers that PCSK-9 inhibitors have. This paper is a review of the literature describing the pleiotropic effects of PCSK-9 inhibitors, which belong to a group of drugs that are being increasingly used, especially when standard lipid-lowering therapy fails. The article focuses on activities other than lipid-lowering, such as the anti-atherosclerotic effect and stabilization of atherosclerotic plaque, the anti-aggregation effect, the anticoagulant effect, the antineoplastic effect, and the ability to influence the course of bacterial infections. In this publication, we try to systematically review the current scientific data, both from our own scientific work and knowledge from international publications.


Assuntos
Pró-Proteína Convertase 9/antagonistas & inibidores , Inibidores de Proteases/farmacologia , Animais , Antibacterianos/farmacologia , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Humanos , Placa Aterosclerótica/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Agregação Patológica de Proteínas/tratamento farmacológico
2.
Medicine (Baltimore) ; 100(10): e25114, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725908

RESUMO

ABSTRACT: It remains uncertain whether statin/ezetimibe combination therapy serves as a useful and equivalent alternative to statin monotherapy for reducing atherosclerotic plaque inflammation. The aim of the present study was to compare the effects of statin/ezetimibe combination therapy and statin monotherapy on carotid atherosclerotic plaque inflammation using 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET)/computed tomography (CT) imaging. Data were pooled from 2 clinical trials that used serial 18FDG PET/CT examination to investigate the effects of cholesterol-lowering therapy on carotid atherosclerotic plaque inflammation. The primary outcome was the percent change in the target-to-background ratio (TBR) of the index vessel in the most diseased segment (MDS) at 6-month follow-up. Baseline characteristics were largely similar between the 2 groups. At the 6-month follow-up, the MDS TBR of the index vessel significantly decreased in both groups. The percent change in the MDS TBR of the index vessel (primary outcome) did not differ significantly between the 2 groups (-8.41 ±â€Š15.9% vs -8.08 ±â€Š17.0%, respectively, P = .936). Likewise, the percent change in the whole vessel TBR of the index vessel did not differ significantly between the 2 groups. There were significant decreases in total and LDL cholesterol levels in both groups at follow-up (P < .001). There were no significant correlations between the percent changes in MDS TBR of the index vessel, changes in the lipid, and high-sensitive C-reactive protein levels. The reduction in carotid atherosclerotic plaque inflammation by statin/ezetimibe combination therapy was equivalent to that by the statin monotherapy.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Doenças das Artérias Carótidas/tratamento farmacológico , Combinação Ezetimiba e Simvastatina/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Placa Aterosclerótica/tratamento farmacológico , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/imunologia , Idoso , Proteína C-Reativa/análise , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/imunologia , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/imunologia , LDL-Colesterol/sangue , Ensaios Clínicos como Assunto , Conjuntos de Dados como Assunto , Feminino , Seguimentos , Humanos , Inflamação/complicações , Inflamação/tratamento farmacológico , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/complicações , Placa Aterosclerótica/imunologia , Rosuvastatina Cálcica/administração & dosagem , Sinvastatina/administração & dosagem
3.
Exp Mol Pathol ; 118: 104604, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33434610

RESUMO

INTRODUCTION AND AIMS: Oxytocin (OT) is a neuropeptide hormone secreted by the posterior pituitary gland. Deficits in OT action have been observed in patients with behavioral and mood disorders, some of which correlate with an increased risk of cardiovascular disease (CVD). Recent research has revealed a wider systemic role that OT plays in inflammatory modulation and development of atherosclerotic plaques. This study investigated the role that OT plays in cholesterol transport and foam cell formation in LPS-stimulated THP-1 human macrophages. METHODS: THP-1 differentiated macrophages were treated with media, LPS (100 ng/ml), LPS + OT (10 pM), or LPS + OT (100 pM). Changes in gene expression and protein levels of cholesterol transporters were analyzed by real time quantitative PCR (RT-qPCR) and Western blot, while oxLDL uptake and cholesterol efflux capacity were evaluated with fluorometric assays. RESULTS: RT-qPCR analysis revealed a significant increase in ABCG1 gene expression upon OT + LPS treatment, compared to LPS alone (p = 0.0081), with Western blotting supporting the increase in expression of the ABCG1 protein. Analysis of oxLDL uptake showed a significantly lower fluorescent value in LPS + OT (100pM) -treated cells when compared to LPS alone (p < 0.0001). While not statistically significant (p = 0.06), cholesterol efflux capacity increased with LPS + OT treatment. CONCLUSION: We demonstrate here that OT can attenuate LPS-mediated lipid accumulation in THP-1 macrophages. These findings support the hypothesis that OT could be used to reduce pro-inflammatory and potentially atherogenic changes observed in patients with heightened CVD risk. This study suggests further exploration of OT effects on monocyte and macrophage cholesterol handling in vivo.


Assuntos
Aterosclerose/tratamento farmacológico , Colesterol/metabolismo , Células Espumosas/efeitos dos fármacos , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Ocitocina/farmacologia , Placa Aterosclerótica/tratamento farmacológico , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Aterosclerose/induzido quimicamente , Aterosclerose/metabolismo , Aterosclerose/patologia , Células Cultivadas , Células Espumosas/metabolismo , Células Espumosas/patologia , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Macrófagos/metabolismo , Macrófagos/patologia , Ocitócicos/farmacologia , Placa Aterosclerótica/induzido quimicamente , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Receptores de Ocitocina/metabolismo
4.
Molecules ; 26(2)2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33419179

RESUMO

A new conjugate of gallato zirconium (IV) phthalocyanine complexes (PcZrGallate) has been obtained from alkilamino-modified SiO2 nanocarriers (SiO2-(CH2)3-NH2NPs), which may potentially be used in photodynamic therapy of atherosclerosis. Its structure and morphology have been investigated. The photochemical properties of the composite material has been characterized. in saline environments when exposed to different light sources Reactive oxygen species (ROS) generation in DMSO suspension under near IR irradiation was evaluated. The PcZrGallate-SiO2 conjugate has been found to induce a cytotoxic effect on macrophages after IR irradiation, which did not correspond to ROS production. It was found that SiO2 as a carrier helps the photosensitizer to enter into the macrophages, a type of cells that play a key role in the development of atheroma. These properties of the novel conjugate may make it useful in the photodynamic therapy of coronary artery disease.


Assuntos
Complexos de Coordenação , Portadores de Fármacos , Indóis , Fotoquimioterapia , Fármacos Fotossensibilizantes , Placa Aterosclerótica , Dióxido de Silício , Zircônio , Animais , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Indóis/química , Indóis/farmacologia , Camundongos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Células RAW 264.7 , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Zircônio/química , Zircônio/farmacologia
5.
Phytomedicine ; 81: 153430, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33341451

RESUMO

BACKGROUND: Atherosclerosis is a chronic vascular disease and characterized by accumulation within the intima of inflammatory cells, smooth muscle cells, lipid, and connective tissue. PURPOSE: The purpose of the present study was to identify natural agents that commonly reverse advanced atherosclerotic plaque to early atherosclerotic plaque. METHODS: Differentially expressed genes (DEGs) were analyzed in silico. The differentially expressed genes from 9 intimal thickening and 8 fibrous cap atheroma tissue which were collected from GEO data were assessed by the connectivity map. Natural candidate securinine, a main compound from Securinega suffruticosa, was selected and administrated 1, 5 mg/kg/day in apolipoprotein-E-deficient (ApoE KO) mice for 18 weeks. RESULTS: Securinine significantly showed lowered blood pressure and improvement of metabolic parameters with hyperlipidemia. The impairment in vasorelaxation was remarkably decreased by treatment with securinine. H&E staining revealed that treatment with securinine reduced atherosclerotic lesions. Securinine suppressed the expression of adhesion molecules and matrix metalloproteinase-2/-9 in both ApoE KO and vascular endothelial cells (HUVEC). In HUVEC pretreatment with securinine significantly inhibited ROS generation and NF-κB activation. Growth curve assays using the real-time cell analyzer showed that securinine significantly decreased TNF-α-induced aortic smooth muscle cell proliferation and migration in a dose-dependent manner. CONCLUSION: Securinine may be a potential natural candidate for the treatment of atherosclerosis because it attenuates vascular inflammation and dysfunction as well as vascular lesion.


Assuntos
Aterosclerose/tratamento farmacológico , Azepinas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Compostos Heterocíclicos de Anel em Ponte/farmacologia , Lactonas/farmacologia , Piperidinas/farmacologia , Substâncias Protetoras/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Aterosclerose/metabolismo , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Knockout para ApoE , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , NF-kappa B/metabolismo , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/metabolismo , Vasodilatação/efeitos dos fármacos
6.
PLoS One ; 15(10): e0239953, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33048950

RESUMO

Atherosclerosis, a chronic inflammatory disorder of the arterial wall, is a complex process whose dynamics are affected by multiple factors. The disease control consists of restraining it by administering statins. Slowing down or halting the plaque growth depends on the patient age at which the statin treatment begins and on the thickness of the intima-media (IMT) at that time. In this paper, we propose a mathematical model to estimate the sets of atherosclerosis states, from which the use of statins can restrain the disease. Our model is control-theoretic, and the estimated sets are the viability kernels, in the parlance of viability theory. To our best knowledge, this way of modelling the atherosclerosis progression is original. We compute two viability kernels, each for a different statin-treatment dose. Each kernel is composed of the vector [age, IMT] from which the disease can be restrained. By extension, the disease can't be restrained from the kernel complements, this being mainly because of the disease and patient-age advancement. The kernels visualise tradeoffs between early and late treatments, which helps the clinician to decide when to start the statin treatment and which statin dose may be sufficient.


Assuntos
Aterosclerose/tratamento farmacológico , Artérias Carótidas , Doenças das Artérias Carótidas/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Placa Aterosclerótica/tratamento farmacológico , Adulto , Idoso , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/patologia , Progressão da Doença , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos
7.
Cochrane Database Syst Rev ; 5: CD012825, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32392374

RESUMO

BACKGROUND: An increasing body of evidence suggests that inflammation plays a key role in stroke, in particular stroke of atherosclerotic origin. Anti-inflammatory medications are a widely heterogeneous group of drugs that are used to suppress the innate inflammatory pathway and thus prevent persistent or recurrent inflammation. Anti-inflammatory agents have the potential to stabilise atherosclerotic plaques by impeding the inflammatory pathway. By targeting specific cytokines, the inflammatory pathway may be interrupted at various stages. OBJECTIVES: To assess the benefits and harms of anti-inflammatory medications plus standard care versus standard care with or without placebo for prevention of vascular events (stroke, myocardial infarction (MI), non-fatal cardiac arrest, unstable angina requiring revascularisation, vascular death) and all-cause mortality in people with a prior history of ischaemic stroke or transient ischaemic attack (TIA). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; last searched 29 May 2019); MEDLINE (1948 to 29 May 2019); Embase (1980 to 29 May 2019); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 29 May 2019); and Scopus (1995 to 29 May 2019). In an effort to identify additional published, unpublished, and ongoing trials, we searched several grey literature sources (last searched 30 May 2019). We incorporated all identified studies into the results section. We applied no restrictions with respect to language, date of publication, or study setting. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) and cluster-randomised controlled trials that evaluated anti-inflammatory medications for prevention of major cardiovascular events following ischaemic stroke or TIA. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed for inclusion titles and abstracts of studies identified by the search. Two review authors independently reviewed full-text articles for inclusion in this review. We planned to assess risk of bias and to apply the GRADE method. MAIN RESULTS: We identified no studies that met the inclusion criteria. AUTHORS' CONCLUSIONS: There is currently a paucity of evidence on the use of anti-inflammatory medications for prevention of major cardiovascular events following ischaemic stroke or TIA. RCTs are needed to assess whether use of anti-inflammatory medications in this setting is beneficial.


Assuntos
Angina Instável/prevenção & controle , Anti-Inflamatórios/uso terapêutico , Parada Cardíaca/prevenção & controle , Ataque Isquêmico Transitório/complicações , Infarto do Miocárdio/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Humanos , Placa Aterosclerótica/complicações , Placa Aterosclerótica/tratamento farmacológico , Prevenção Secundária/métodos , Acidente Vascular Cerebral/etiologia
8.
Life Sci ; 254: 117756, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32389832

RESUMO

Polydatin (PD) is a monocrystalline metabolite from the underground parts of Polygonum cuspidatum Sieb. et Zucc., a member of the Polygonaceae family, which has been traditionally used in Asian countries as both foodstuffs and medicine. PD, also reckoned as pieceid, 3,4',5-trihydroxystilbene-3-ß-D-glucoside, (E)-piceid, (E)-polydatin, and trans-polydatin. It possesses potent biological activities i.e. analgesic, anti-inflammatory, antidiabetic, anticancer, and anti-atherosclerotic properties. The initial part of this report specifically explains distinct sequential mechanisms underlying the initiation and development of atherosclerotic plaques and later part deals with the pharmacological efficacy of PD in the management of major cardiac event i.e. atherosclerotic cardiovascular diseases (ASCVD) via modulation of a set of molecular mechanisms i.e. antioxidant potential, lipid and lipoprotein metabolism including total cholesterol (TC) and low density lipoprotein (LDL) levels, ß-hydroxy-ß-methyl-glutaryl-CoA reductase (HMG-R) expression and functionality, SIRT signalling, LDL-receptor (LDL-R), LDL oxidation status (Ox-LDL), effects on endothelial cells (ECs), smooth muscle cells (SMCs), macrophage, foam cell formation and plaque stabilization, inflammatory signalling pathways and hypertension. In contrast, one of the major insight into the potential cardioprotective molecular mechanism is the PD-mediated targeting of proprotein convertase subtilisin/kexin type-9 (PCSK-9) and LDL-R pathway, both at transcriptional and protein functional level, which makes it a better alternative therapeutic medicinal candidate to treat hypercholesterolemia, especially for the patients facing inadequate lipid lowering with classical HMG-R inhibitors (statins) and statin intolerance. Finally, to sum up the whole, we concluded that PD may be promoted from alternative to mainstream medicine in targeting risk factors mediated ASCVD.


Assuntos
Aterosclerose/tratamento farmacológico , Glucosídeos/farmacologia , Estilbenos/farmacologia , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/metabolismo , Células Endoteliais/metabolismo , Fallopia japonica/metabolismo , Glucosídeos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Lipoproteínas LDL , Placa Aterosclerótica/tratamento farmacológico , Receptores de LDL/metabolismo , Fatores de Risco , Estilbenos/uso terapêutico
9.
J Pharmacol Exp Ther ; 373(3): 463-475, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32238453

RESUMO

Leonurine (LEO) is a bioactive small molecular compound that has protective effects on the cardiovascular system and prevents the early progression of atherosclerosis; however, it is not clear whether LEO is effective for plaque stability. A novel mouse atherosclerosis model involving tandem stenosis (TS) of the right carotid artery combined with western diet (WD) feeding was used. Apolipoprotein E gene-deficient mice were fed with a WD and received LEO administration daily for 13 weeks. TS was introduced 6 weeks after the onset of experiments. We found that LEO enhanced plaque stability by increasing fibrous cap thickness and collagen content while decreasing the population of CD68-positive cells. Enhanced plaque stability by LEO was associated with the nitric oxide synthase (NOS)-nitric oxide (NO) system. LEO restored the balance between endothelial NOS(E)- and inducible NOS(iNOS)-derived NO production; suppressed the NF-κB signaling pathway; reduced the level of the inflammatory infiltration in plaque, including cytokine interleukin 6; and downregulated the expression of adhesion molecules. These findings support the distinct role of LEO in plaque stabilization. In vitro studies with oxidized low-density lipoprotein-challenged human umbilical vein endothelial cells revealed that LEO balanced NO production and inhibited NF-κB/P65 nuclear translocation, thus mitigating inflammation. In conclusion, the restored balance of the NOS-NO system and mitigated inflammation contribute to the plaque-stabilizing effect of LEO. SIGNIFICANCE STATEMENT: LEO restored the balance between endothelial NOS and inducible NOS in NO production and inhibited excessive inflammation in atherosclerotic "unstable" and rupture-prone plaques in apolipoprotein E gene-deficient mice. The protective effect of LEO for stabilizing atherosclerotic plaques was due to improved collagen content, increased fibrous cap thickness, and decreased accumulation of macrophages/foam cells. So far, LEO has passed the safety and feasibility test of phase I clinical trial.


Assuntos
Aterosclerose/tratamento farmacológico , Ácido Gálico/análogos & derivados , Inflamação/tratamento farmacológico , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/metabolismo , Placa Aterosclerótica/tratamento farmacológico , Animais , Aterosclerose/metabolismo , Linhagem Celular , Ácido Gálico/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Placa Aterosclerótica/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
Annu Rev Med ; 71: 191-201, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31986087

RESUMO

The development of potent cholesterol-reducing medications in the last decade of the twentieth century has altered the approach to prevention and treatment of cardiovascular disease (CVD). Initial experience with statins, and more recently with the addition of PCSK9 inhibitors, has proven that human CVD, like that in animal models, can be halted and regressed. Available clinical data show that the lower the achieved level of low-density lipoprotein cholesterol, the greater the regression of disease. Investigative studies are now aimed to understand those factors that both accelerate and impede this healing process. Some of these are likely to be modifiable, and the future of atherosclerotic CVD treatment is likely to be early screening, use of measures to repair atherosclerotic arteries, and prevention of most CVD events.


Assuntos
Aterosclerose/metabolismo , Placa Aterosclerótica/metabolismo , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , Colesterol/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Quilomícrons/metabolismo , Angiografia por Tomografia Computadorizada , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Macrófagos/metabolismo , Imagem por Ressonância Magnética , Camundongos , Camundongos Knockout , Camundongos Knockout para ApoE , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/prevenção & controle , Pró-Proteína Convertase 9/antagonistas & inibidores , Coelhos , Ratos , Receptores de LDL/genética , Receptores de LDL/metabolismo , Indução de Remissão , Triglicerídeos/metabolismo , Ultrassonografia de Intervenção
11.
Biochem Biophys Res Commun ; 524(2): 308-316, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-31987499

RESUMO

BACKGROUND: Atherosclerotic plaque rupture is the major trigger of acute cardiovascular risk events, and manipulation of M1/M2 macrophage homeostasis is an effective strategy for regulating atherosclerotic plaque stability. This study was aimed to illuminate the effects of oleoylethanolamide (OEA) on macrophage polarization and plaque stability. METHODS: Macrophages derived from THP-1 were treated with OEA followed by LPS/IFN-γ, and the markers of M1, M2 macrophages were monitored by western blot, real-time PCR and immunofluorescence staining. The effect of OEA on macrophage polarization in the arch of aortic arteries was tested by immunofluorescence staining and western blot, and the plaque stability was completed by Masson's trichrome and hematoxylin and eosin (HE) in apolipoprotein E (ApoE)-/- mice. RESULTS: OEA treatment enhanced the expression of two classic M2 macrophage markers, macrophage mannose receptor (CD206) and transforming growth factor (TGF-ß), while the expression of iNOS (M1 macrophages) was decreased in THP-1-derived macrophages. Blocking of PPARα using siRNA and inhibition of AMP-activated protein kinase (AMPK) by its inhibitor compound C attenuated the OEA-induced expression of M2 macrophage markers. In addition, OEA significantly suppressed M1, promoted M2 macrophage polarization, increased collagen content and decreased necrotic core size in atherosclerotic plaques in ApoE-/- mice, which were linked with the expression of PPARα. CONCLUSIONS: OEA improved atherosclerotic plaque stability through regulating macrophage polarization via AMPK-PPARα pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/imunologia , Anti-Inflamatórios/uso terapêutico , Endocanabinoides/uso terapêutico , Macrófagos/efeitos dos fármacos , Ácidos Oleicos/uso terapêutico , PPAR alfa/imunologia , Placa Aterosclerótica/tratamento farmacológico , Animais , Humanos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Camundongos , Placa Aterosclerótica/imunologia , Placa Aterosclerótica/patologia , Transdução de Sinais/efeitos dos fármacos , Células THP-1
12.
Stroke ; 51(3): 938-943, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31893985

RESUMO

Background and Purpose- Atrial cardiopathy and atherosclerotic plaque are two potential mechanisms underlying embolic strokes of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. A better understanding of their association may inform targeted secondary prevention strategies. Methods- We examined the association between atrial cardiopathy and atherosclerotic plaque in the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), which enrolled 7213 patients with recent ESUS during 2014 to 2017. For this analysis, we included patients with data on left atrial dimension, location of brain infarction, and cervical large artery plaque. The variables of primary interest were left atrial diameter and cervical plaque ipsilateral to brain infarction. Secondary markers of atrial cardiopathy were premature atrial contractions on Holter monitoring and newly diagnosed atrial fibrillation. For descriptive purposes, left atrial enlargement was defined as ≥4.7 cm. Multivariable logistic regression was used to examine the association between atrial cardiopathy markers and ipsilateral plaque after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, current smoking, and hyperlipidemia. Results- Among 3983 eligible patients, 235 (5.9%) had left atrial enlargement, 939 (23.6%) had ipsilateral plaque, and 94 (2.4%) had both. Shared risk factors for left atrial enlargement and ipsilateral plaque were male sex, white race, hypertension, tobacco use, and coronary artery disease. Despite shared risk factors, increasing left atrial dimension was not associated with ipsilateral plaque after adjustment for covariates (odds ratio per cm, 1.1 [95% CI, 1.0-1.2]; P=0.08). We found no consistent associations between secondary markers of atrial cardiopathy and ipsilateral plaque. Conclusions- In a large population of patients with ESUS, we did not observe a notable association between atrial cardiopathy and atherosclerotic plaque, and few patients had both conditions. These findings suggest that atrial cardiopathy and atherosclerotic plaque may be distinct, nonoverlapping risk factors for stroke among ESUS patients.


Assuntos
Infarto Encefálico , Cardiomegalia , Embolia Intracraniana , Placa Aterosclerótica , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral , Idoso , Biomarcadores/sangue , Infarto Encefálico/sangue , Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/fisiopatologia , Cardiomegalia/sangue , Cardiomegalia/tratamento farmacológico , Cardiomegalia/fisiopatologia , Feminino , Átrios do Coração/fisiopatologia , Humanos , Embolia Intracraniana/sangue , Embolia Intracraniana/tratamento farmacológico , Embolia Intracraniana/fisiopatologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/fisiopatologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia
13.
Lipids Health Dis ; 19(1): 6, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931807

RESUMO

BACKGROUND: The HMG-CoA reductase is key enzyme of cholesterol biosynthesis which potentially contributes in management of hypercholesterolemia. The present study was designed to assess the inhibitory effect of phytoconstituents of an ethanolic extract of Prosopis cineraria pods on HMG - CoA reductase and regression potential of atherosclerotic plaque. METHODS: Healthy, adult male, albino rabbits in which hypercholesterolemia was induced by supplying the high fat diet and a supplement of cholesterol powder with coconut oil (500 mg/5 ml/Day/kg body weight) for 15 days, were used as a disease model. Phytochemical analysis of an ethanolic extract Prosopis cineraria pods was conducted using LCMS, GCMS and FTIR analysis. Further, in-vitro, in-vivo and in-silico assessments were performed. RESULTS: The in-vitro assessment of HMG -CoA reductase activity indicated a 67.1 and 97.3% inhibition by the extract and a standard drug (Pravastatin), respectively. Additionally, an in-silico evaluation was made using appropriate docking software and results also indicated as significant interactions of the identified compounds with the target enzyme. Treatment of rabbits with the ethanolic extract of P. cineraria pod resulted in significant (P ≤ 0.001) reductions in total cholesterol, LDL cholesterol, VLDL cholesterol, and triglyceride. Accordingly, reductions were occurred in atherosclerotic plaque, intima and media of aortal wall along with lumen volume of the aorta significantly increased (P ≤ 0.001). CONCLUSION: It can be illustrating that the ethanolic extract of Prosopis cineraria pod contains potent bioactive phytocompounds might be inhibit HMG - CoA reductase and have regression potential of atherosclerotic plaque.


Assuntos
Anticolesterolemiantes/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Placa Aterosclerótica/tratamento farmacológico , Prosopis/química , Animais , Anticolesterolemiantes/química , HDL-Colesterol/sangue , LDL-Colesterol/sangue , VLDL-Colesterol/sangue , Modelos Animais de Doenças , Hidroximetilglutaril-CoA Redutases/genética , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Hipercolesterolemia/tratamento farmacológico , Masculino , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Placa Aterosclerótica/sangue , Placa Aterosclerótica/patologia , Pravastatina/farmacologia , Coelhos , Triglicerídeos/sangue
14.
Artif Cells Nanomed Biotechnol ; 48(1): 169-179, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852323

RESUMO

Magnetic resonance imaging (MRI) is an essential tool for the diagnosis of atherosclerosis, a chronic cardiovascular disease. MRI primarily uses superparamagnetic iron oxide (SPIO) as a contrast agent. However, SPIO integrated with therapeutic drugs has rarely been studied. In this study, we explored biocompatible paramagnetic iron-oxide nanoparticles (NPs) in a complex with low pH-sensitive cyclodextrin for the diagnostic imaging and treatment of atherosclerosis. The NPs were conjugated with profilin-1 antibody (PFN1) to specifically target vascular smooth muscle cells (VSMCs) in the atherosclerotic plaque and integrated with the anti-inflammatory drug, rapamycin. The PFN1-CD-MNPs were easily binded to the VSMCs, indicating their good biocompatibility and low renal toxicity over the long term. Ex vivo near-infrared fluorescence (NIRF) imaging and in vivo MRI indicated the accumulation of PFN1-CD-MNPs in the atherosclerotic plaque. The RAP@PFN1-CD-MNPs alleviated the progression of arteriosclerosis. Thus, PFN1-CD-MNPs served not only as multifunctional imaging probes but also as nanovehicles for the treatment of atherosclerosis.


Assuntos
Imagem por Ressonância Magnética , Nanomedicina , Imagem Óptica , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/tratamento farmacológico , Animais , Apolipoproteínas E/deficiência , Meios de Contraste/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Lipídeos/sangue , Nanopartículas de Magnetita/química , Masculino , Camundongos , Placa Aterosclerótica/sangue , Placa Aterosclerótica/metabolismo , Sirolimo/química , Sirolimo/farmacologia , Sirolimo/uso terapêutico
15.
Biochem Biophys Res Commun ; 522(2): 512-517, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-31784089

RESUMO

Combined LXR ligand (T0901317) and MEK1/2 inhibitor (U0126) not only reduces atherosclerosis in apoE deficient mice, but also blocks LXR ligand-induced fatty liver and hypertriglyceridemia. However, the atheroprotective function of combined T0901317 and U0126 should be further investigated in LDLR deficient (LDLR-/-) mice since deficiency of LDLR not apoE can occur to humans with a high frequency. Herein, we validated the effectiveness of this combinational therapy on the development of atherosclerosis in LDLR-/- mice to demonstrate its potential application in clinic. We found although T0901317 or U0126 alone reduced atherosclerotic plaques in en face and aortic root areas in HFD-fed LDLR-/- mice, their combination inhibited lesions in a synergistic manner. Combined U0126 and T0901317 had no effect on serum total cholesterol levels. T0901317 deceased HDL-cholesterol levels, which was restored by combined U0126. Meanwhile, U0126 alleviated T0901317-induced triglyceride accumulation, the major adverse effect of T0901317 which limits its clinical utility. Mechanistically, U0126 reduced fatty acid de novo synthesis by inhibiting hepatic fatty acid synthase (FASN) expression, thereby correcting T0901317-induced triglyceride overproduction. In conclusion, our study demonstrates that combination of MEK1/2 inhibitor and LXR ligand can synergistically reduce atherosclerosis in LDLR deficient mice without lipogenic side effects.


Assuntos
Aterosclerose/tratamento farmacológico , Receptores X do Fígado/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Receptores de LDL/deficiência , Animais , Aterosclerose/sangue , Aterosclerose/complicações , Butadienos/farmacologia , Butadienos/uso terapêutico , Sinergismo Farmacológico , Fígado Gorduroso/sangue , Fígado Gorduroso/complicações , Fígado Gorduroso/tratamento farmacológico , Feminino , Hipertrigliceridemia/sangue , Hipertrigliceridemia/complicações , Ligantes , Lipídeos/sangue , Masculino , Camundongos Knockout , Nitrilos/farmacologia , Nitrilos/uso terapêutico , Placa Aterosclerótica/sangue , Placa Aterosclerótica/complicações , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/patologia , Receptores de LDL/metabolismo
16.
Biomed Pharmacother ; 123: 109729, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31887543

RESUMO

Tanshinone IIA (TS IIA) and Astragaloside IV (AS IV) are natural herbal products which exert anti-inflammatory and anti-oxidant effects in order to eliminate unstable plaque in atherosclerosis. However, the combined effect of these two drugs on atherosclerotic plaque vulnerability and its molecular mechanism remains unclear. In the current study, we evaluate the effects of TS IIA and AS IV on atherosclerotic unstable plaque stability, and then further explore the mechanism of TS IIA and AS IV intervention on unstable plaque in vivo and in vitro. Histological characterization of atherosclerotic plaques was measured by Hematoxylin-Eosin (HE), Masson's Trichrome and Oil Red O staining. Cellular lipid droplet was measured by Oil Red O staining. The size of atherosclerotic lesion areas and content of lipids and collagen in the right common carotid arteries of apoE-/- mice were examined by Hematoxylin-Eosin (HE), Oil-red O, and Masson staining, respectively. The protein expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α and C-reactive protein (CRP) in ApoE-/- mice and RAW264.7 cells were determined by enzyme-linked immunosorbent assay. The protein expression levels of matrix metalloproteinase-9 (MMP-9) and endothelial nitric oxide synthase (eNOS) in ApoE-/- mice and RAW264.7 cells were determined by western blotting. In addition, the PI3K/AKT and TRL4/NF-κB signaling were determined by western blotting. Our results revealed that the combination of TS IIA and AS IV significantly decreased lipid areas, increased collagen content and thickened fibrous cap in the right common carotid arteries compared with ApoE (-/-) mice model group. TS IIA and AS IV visibly reduced the cytoplasmic lipid droplet accumulation induced by oxLDL in RAW 264.7 macrophages. The ApoE-/- mice model group and oxLDL -stimulated RAW 264.7 macrophages treated with TS IIA and AS IV showed a downregulation in IL-6, MMP-9, TNF-α and CRP protein expression and upregulation in eNOS protein expression. Furthermore, TSIIA and AS IV may activate PI3K/AKT signaling and suppress TLR4/NF-κB signaling in vivo and in vitro. Additionally, blocking the PI3K/Akt signaling enhanced the translocation of NF-κB to the nucleus, TLR4, IL-6, MMP-9, TNF-α and CRP expression and inhibited eNOS expression in TS IIA and AS IV-treated RAW 264.7 macrophages. Therefore, the present study implicates that TS IIA and AS IV reinforces plaque stability via PI3K/AKT and TLR4/NF-κB signaling. TS IIA and AS IV administration may provide the basis for a potential therapeutic approach for the inhibition of vulnerable atherosclerotic plaques.


Assuntos
Abietanos/administração & dosagem , Apolipoproteínas E/genética , Placa Aterosclerótica/tratamento farmacológico , Saponinas/administração & dosagem , Triterpenos/administração & dosagem , Abietanos/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Modelos Animais de Doenças , Quimioterapia Combinada , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Knockout , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Placa Aterosclerótica/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células RAW 264.7 , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologia
17.
Redox Biol ; 28: 101338, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31634818

RESUMO

NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are instrumental in all inflammatory phases of atherosclerosis. Dysregulated histone deacetylase (HDAC)-related epigenetic pathways have been mechanistically linked to alterations in gene expression in experimental models of cardiovascular disorders. Hitherto, the relation between HDAC and Nox in atherosclerosis is not known. We aimed at uncovering whether HDAC plays a role in mediating Nox up-regulation, oxidative stress, inflammation, and atherosclerotic lesion progression. Human non-atherosclerotic and atherosclerotic arterial samples, ApoE-/- mice, and in vitro polarized monocyte-derived M1/M2-macrophages (Mac) were examined. Male ApoE-/- mice, maintained on normal or high-fat, cholesterol-rich diet, were randomized to receive 10 mg/kg suberoylanilide hydroxamic acid (SAHA), a pan-HDAC inhibitor, or its vehicle, for 4 weeks. In the human/animal studies, real-time PCR, Western blot, lipid staining, lucigenin-enhanced chemiluminescence assay, and enzyme-linked immunosorbent assay were employed. The protein levels of class I, class IIa, class IIb, and class IV HDAC isoenzymes were significantly elevated both in human atherosclerotic tissue samples and in atherosclerotic aorta of ApoE-/- mice. Treatment of ApoE-/- mice with SAHA reduced significantly the extent of atherosclerotic lesions, and the aortic expression of Nox subtypes, NADPH-stimulated ROS production, oxidative stress and pro-inflammatory markers. Significantly up-regulated HDAC and Nox subtypes were detected in inflammatory M1-Mac. In these cells, SAHA reduced the Nox1/2/4 transcript levels. Collectively, HDAC inhibition reduced atherosclerotic lesion progression in ApoE-/- mice, possibly by intertwined mechanisms involving negative regulation of Nox expression and inflammation. The data propose that HDAC-oriented pharmacological interventions could represent an effective therapeutic strategy in atherosclerosis.


Assuntos
Apolipoproteínas E/deficiência , Aterosclerose/etiologia , Aterosclerose/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , NADPH Oxidases/genética , Estresse Oxidativo/efeitos dos fármacos , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Biópsia , LDL-Colesterol/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Epigênese Genética , Humanos , Masculino , Camundongos , Camundongos Knockout , NADPH Oxidases/metabolismo , Oxirredução , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Espécies Reativas de Oxigênio/metabolismo
18.
Int J Cardiol ; 299: 249-253, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31409515

RESUMO

BACKGROUND: ATP-binding cassette A1 (ABCA1) and G1 (ABCG1) mediate cholesterol efflux from lipid-laden macrophages, thus promoting anti-atherosclerotic outcomes. The mechanism(s) linking treatment with statins and ABCA1/ABCG1 in human atherosclerosis are not fully understood and require further investigation. Therefore, we studied whether short-term treatment with low- or high-dose rosuvastatin may affect ABCA1 and ABCG1 expression in human atherosclerotic plaques. METHODS: Seventy patients with severe stenosis of the internal carotid artery were randomized to receive low (10 mg/day) or high (40 mg/day) dose rosuvastatin for 12 weeks before elective endarterectomy. As controls, we analyzed a reference group of 10 plaques from subjects with hypercholesterolemia but not receiving statin treatment and an additional set of 11 plaques collected from normocholesterolemic patients. On atherosclerotic plaques, ABCA1 and ABCG1 expression was evaluated at RNA level by qPCR and at protein level by immunoblotting and immunohistochemistry. RESULTS: Both rosuvastatin doses were associated with lower plaque ABCA1 mRNA levels and with a trend toward reduction for ABCG1. However, ABCA1 protein was paradoxically higher in patients treated with high-dose rosuvastatin and was associated with lower levels of miR-33b-5p, a microRNA known as a regulator of ABCA1. Multivariate analyses showed that the effect is cholesterol-independent. Finally, no effects were found for ABCG1 protein. CONCLUSIONS: High-dose rosuvastatin increases macrophage ABCA1 protein levels in human atherosclerotic plaque despite mRNA reduction in a mechanism unrelated to plasma cholesterol reduction and potentially involving miR-33b-5p. This pathway may reflect an additional feature contributing to the anti-atherosclerotic effect for high-dose rosuvastatin. TRIAL REGISTRATION: ISRCTN16590640.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/sangue , Colesterol/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Placa Aterosclerótica/sangue , Placa Aterosclerótica/tratamento farmacológico , Rosuvastatina Cálcica/administração & dosagem , Transportador 1 de Cassete de Ligação de ATP/biossíntese , Idoso , Idoso de 80 Anos ou mais , Anticolesterolemiantes/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino
19.
J Clin Lipidol ; 13(5): 847-853, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31783975

RESUMO

BACKGROUND: Statin therapy can improve plaque stability. However, the time course of effects of statin on adventitial angiogenesis and plaque neovascularization has not been studied. OBJECTIVE: The objective of the study was to investigate whether statin therapy reduces plaque neovascularization, associated with adventitial angiogenesis, over 24 months as assessed by using carotid dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: Forty-three lipid treatment-naïve subjects with asymptomatic carotid atherosclerosis received rosuvastatin (5-20 mg/d) to lower low-density lipoprotein cholesterol to <80 mg/dL for 24 months. Carotid DCE-MRI was performed at baseline, 3, 12 and 24 months. Vascularity (Vp = fractional plasma volume) and vascular permeability (Ktrans = transfer constant) derived from kinetic modeling of DCE-MRI were measured in both adventitia and plaque. RESULTS: Adventitia Vp and adventitia Ktrans were significantly correlated with plaque Vp and plaque Ktrans at baseline. Rosuvastatin significantly reduced both adventitial and plaque Vp significantly at 3 months from 0.121 ± 0.064 to 0.085 ± 0.049 (P = .008) and from 0.096 ± 0.052 to 0.067 ± 0.043 (P = .013). Adventitial and plaque Vp continued to decrease by 43% and 34% at 12 months and by 49% and 45% at 24 months. However, the continued reductions from 3 to 12 months and from 12 to 24 months were not statistically significant. Adventitial and plaque Ktrans showed similar trends, but nonstatistically significant decreases during the 24 months of treatment. CONCLUSIONS: Rosuvastatin therapy rapidly and significantly decreased adventitial and plaque neovascularization at 3 months followed by continued, but nonstatistically significant, decreases at 12 and 24 months.


Assuntos
Túnica Adventícia/patologia , Artérias Carótidas/patologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neovascularização Fisiológica/efeitos dos fármacos , Placa Aterosclerótica/tratamento farmacológico , Rosuvastatina Cálcica/uso terapêutico , Túnica Adventícia/diagnóstico por imagem , Túnica Adventícia/efeitos dos fármacos , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/efeitos dos fármacos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lipídeos/sangue , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico por imagem , Rosuvastatina Cálcica/farmacologia , Fatores de Tempo
20.
Sci Rep ; 9(1): 17937, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784656

RESUMO

Diabetes worsens atherosclerosis progression and leads to a defect in repair of arteries after cholesterol reduction, a process termed regression. Empagliflozin reduces blood glucose levels via inhibition of the sodium glucose cotransporter 2 (SGLT-2) in the kidney and has been shown to lead to a marked reduction in cardiovascular events in humans. To determine whether glucose lowering by empagliflozin accelerates atherosclerosis regression in a mouse model, male C57BL/6J mice were treated intraperitoneally with LDLR- and SRB1- antisense oligonucleotides and fed a high cholesterol diet for 16 weeks to induce severe hypercholesterolemia and atherosclerosis progression. At week 14 all mice were rendered diabetic by streptozotocin (STZ) injections. At week 16 a baseline group was sacrificed and displayed substantial atherosclerosis of the aortic root. In the remaining mice, plasma cholesterol was lowered by switching to chow diet and treatment with LDLR sense oligonucleotides to induce atherosclerosis regression. These mice then received either empagliflozin or vehicle for three weeks. Atherosclerotic plaques in the empagliflozin treated mice were significantly smaller, showed decreased lipid and CD68+ macrophage content, as well as greater collagen content. Proliferation of plaque resident macrophages and leukocyte adhesion to the vascular wall were significantly decreased in empagliflozin-treated mice. In summary, plasma glucose lowering by empagliflozin improves plaque regression in diabetic mice.


Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/etiologia , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Glucosídeos/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Animais , Aterosclerose/sangue , Glicemia/análise , Diabetes Mellitus Experimental/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Placa Aterosclerótica/sangue , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/etiologia
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