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1.
Biochem Biophys Res Commun ; 703: 149667, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38382362

RESUMO

Trimethylamine N-oxide (TMAO) is a novel risk factor for atherosclerosis, and its underlying regulatory mechanisms are under intensive investigation. Inflammation-related vascular endothelial damage is the major driver in atherogenic process. Pyroptosis, a type of proinflammatory programmed cell death, has been proved to promote the initiation and progression of atherosclerosis. In our study, we found that TMAO triggered endothelial cells excessive mitophagy, thereby facilitating pyroptosis. This process is mediated by the upexpression of phosphatidylethanolamine acyltransferase (LPEAT). These findings provide insights into TMAO-induced vascular endothelial cell damage and suggest that LPEAT may be a valuable target for the prevention and treatment of atherosclerosis.


Assuntos
Aterosclerose , Células Endoteliais , Humanos , Células Endoteliais/metabolismo , Piroptose , Mitofagia , Metilaminas/farmacologia , Metilaminas/metabolismo , Aterosclerose/metabolismo
2.
Nitric Oxide ; 142: 47-57, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38049061

RESUMO

BACKGROUND: Endothelial-mesenchymal transition (EndMT) induced by low shear stress plays an important role in the development of atherosclerosis. However, little is known about the correlation between hydrogen sulfide (H2S), a protective gaseous mediator in atherosclerosis and the process of EndMT. METHODS: We constructed a stable low-shear-stress-induced(2 dyn/cm2) EndMT model, acombined with the pretreatment method of hydrogen sulfide slow release agent(GYY4137). The level of MEST was detected in the common carotid artery of ApoE-/- mice with local carotid artery ligation. The effect of MEST on atherosclerosis development in vivo was verified using ApoE-/- mice were given tail-vein injection of endothelial-specific overexpressed and knock-down MEST adeno-associated virus (AAV). RESULTS: These findings confirmed that MEST is up-regulated in low-shear-stress-induced EndMT and atherosclerosis. In vivo experiments showed that MEST gene overexpression significantly promoted EndMT and aggravated the development of atherosclerotic plaques and MEST gene knockdown significantly inhibited EndMT and delayed the process of atherosclerosis. In vitro, H2S inhibits the expression of MEST and EndMT induced by low shear stress and inhibits EndMT induced by MEST overexpression. Knockdown of NFIL3 inhibit the up regulation of MEST and EndMT induced by low shear stress in HUVECs. CHIP-qPCR assay and Luciferase Reporter assay confirmed that NFIL3 binds to MEST DNA, increases its transcription and H2S inhibits the binding of NFIL3 and MEST DNA, weakening NFIL3's transcriptional promotion of MEST. Mechanistically, H2S increased the sulfhydrylation level of NFIL3, an important upstream transcription factors of MEST. In part, transcription factor NFIL3 restrain its binding to MEST DNA by sulfhydration. CONCLUSIONS: H2S negatively regulate the expression of MEST by sulfhydrylation of NFIL3, thereby inhibiting low-shear-stress-induced EndMT and atherosclerosis.


Assuntos
Aterosclerose , Sulfeto de Hidrogênio , Camundongos , Animais , Humanos , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/metabolismo , Transição Endotélio-Mesênquima , Aterosclerose/genética , Aterosclerose/metabolismo , Endotélio/metabolismo , DNA/metabolismo , Apolipoproteínas E/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Transição Epitelial-Mesenquimal
3.
Am J Pathol ; 193(10): 1485-1500, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37481069

RESUMO

Mitochondria are cellular power stations and essential organelles for maintaining cellular homeostasis. Dysfunctional mitochondria have emerged as a key factor in the occurrence and development of cardiovascular disease. This review focuses on advances in the relationship between mitochondrial dysfunction and cardiovascular diseases such as atherosclerosis, heart failure, myocardial ischemia reperfusion injury, and pulmonary arterial hypertension. The clinical value and challenges of mitochondria-targeted strategies, including mitochondria-targeted antioxidants, mitochondrial quality control modulators, mitochondrial function protectors, mitochondrial biogenesis promoters, and recently developed mitochondrial transplants, are also discussed.


Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Traumatismo por Reperfusão Miocárdica , Humanos , Doenças Cardiovasculares/terapia , Mitocôndrias , Antioxidantes
4.
Curr Med Chem ; 30(38): 4355-4373, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36464879

RESUMO

Atherosclerosis (AS) is the major factor of cardiovascular disease (CVD) and is characterized by a progressive and chronic inflammatory process in the arterial wall. Recent studies have shown that disruption of the mitochondrial membrane potential (deltapsi (m)) directly affects the electron transport chain (ETC), which in turn leads to oxidative stress, and furthermore, its alteration leads to apoptosis and activation of the NLRP3 inflammasome, thereby promoting the development of AS. Here, this review describes how deltapsi (m) contributes to the development of AS by mediating oxidative stress, apoptosis, and NLRP3 inflammasome activation, and potential AS intervention strategies by targeting oxidative stress, apoptosis, and NLRP3 inflammasome activation induced by deltapsi (m).


Assuntos
Aterosclerose , Inflamassomos , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Mitocôndrias/metabolismo , Potencial da Membrana Mitocondrial , Espécies Reativas de Oxigênio/metabolismo , Aterosclerose/metabolismo
5.
Front Cardiovasc Med ; 9: 909178, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035922

RESUMO

Hydrogen sulfide (H2S), a gas transmitter found in eukaryotic organisms, plays an essential role in several physiological processes. H2S is one of the three primary biological gas transmission signaling mediators, along with nitric oxide and carbon monoxide. Several animal and in vitro experiments have indicated that H2S can prevent coronary endothelial mesenchymal transition, reduce the expression of endothelial cell adhesion molecules, and stabilize intravascular plaques, suggesting its potential role in the treatment of atherosclerosis (AS). H2S donors are compounds that can release H2S under certain circumstances. Development of highly targeted H2S donors is a key imperative as these can allow for in-depth evaluation of the anti-atherosclerotic effects of exogenous H2S. More importantly, identification of an optimal H2S donor is critical for the creation of H2S anti-atherosclerotic prodrugs. In this review, we discuss a wide range of H2S donors with anti-AS potential along with their respective transport pathways and design-related limitations. We also discuss the utilization of nano-synthetic technologies to manufacture H2S donors. This innovative and effective design example sheds new light on the production of highly targeted H2S donors.

6.
DNA Cell Biol ; 41(10): 851-860, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36036955

RESUMO

Autophagy maintains intracellular homeostasis in the cardiovascular system, including in cardiomyocytes, endothelial cells (ECs), and arterial smooth muscle cells. Mitophagy, a selective autophagy that specifically removes damaged and dysfunctional mitochondria, is particularly important for cardiovascular homeostasis. Dysfunctional mitophagy contributes to cardiovascular disease, particularly atherosclerosis (AS). This review focuses on the advances of regulator mechanisms of mitophagy and its potential roles in AS. The findings are beneficial to understanding the pathological processes of atherosclerotic lesions and provide new ideas for the prevention and clinical treatment of AS.


Assuntos
Aterosclerose , Mitofagia , Humanos , Mitofagia/fisiologia , Células Endoteliais , Autofagia/fisiologia , Mitocôndrias/patologia , Aterosclerose/patologia
7.
DNA Cell Biol ; 41(3): 285-291, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35138943

RESUMO

Succinate is an important intermediate product of mitochondrial energy metabolism. Recent studies revealed that beyond its known traditional metabolic functions, succinate plays important roles in signal transduction, immunity, inflammation, and posttranslational modification. Recent studies showed that patients and mouse models with cardiovascular disease have high levels of serum succinate and succinate accumulation. Atherosclerosis (As) is the pathological basis of cardiovascular and peripheral vascular diseases, such as coronary heart disease, cerebral infarction, and peripheral vascular disease, and is a major factor affecting human health. This article reviews the progression of succinate in As diseases and its underlying mechanisms.


Assuntos
Aterosclerose/etiologia , Aterosclerose/metabolismo , Ácido Succínico/metabolismo , Animais , Aterosclerose/patologia , Progressão da Doença , Células Endoteliais/fisiologia , Humanos , Macrófagos/classificação , Macrófagos/fisiologia , Camundongos , Modelos Cardiovasculares , Miócitos de Músculo Liso/patologia , Miócitos de Músculo Liso/fisiologia , Estresse Oxidativo , Sistema Renina-Angiotensina/fisiologia , Transdução de Sinais
8.
Curr Med Chem ; 29(13): 2322-2333, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34365937

RESUMO

The tricarboxylic acid (TCA) cycle is the center of energy metabolism in eukaryotic cells and is dynamically adjusted according to the energy needs of cells. Macrophages are activated by inflammatory stimuli, and then two breakpoints in TCA cycle lead to the accumulation of intermediates. Atherosclerosis is a chronic inflammatory process. Here, the "non-metabolic" signaling functions of TCA cycle intermediates in the macrophage under inflammatory stimulation and the role of intermediates in the progression of atherosclerosis are discussed.


Assuntos
Aterosclerose , Ciclo do Ácido Cítrico , Aterosclerose/metabolismo , Metabolismo Energético , Humanos , Inflamação/metabolismo , Macrófagos/metabolismo
9.
DNA Cell Biol ; 40(12): 1495-1502, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34931866

RESUMO

The cytoskeleton is a biopolymer network composed of intermediate filaments, actin, and microtubules, which is the main mechanical structure of cells. Vimentin is an intermediate filament protein that regulates the mechanical and contractile properties of cells, thereby reflecting their mechanical properties. In recent years, the "nonmechanical function" of vimentin inside and outside of cells has attracted extensive attention. The content of vimentin in atherosclerotic plaques is increased, and the serum secretion of vimentin in patients with coronary heart disease is remarkably increased. In this review, the mechanistic and nonmechanistic roles of vimentin in atherosclerosis progression were summarized on the basis of current studies.


Assuntos
Aterosclerose/metabolismo , Vimentina/metabolismo , Animais , Doença das Coronárias/metabolismo , Citoesqueleto/metabolismo , Humanos
10.
Cell Cycle ; 20(15): 1477-1486, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34266366

RESUMO

Endothelial-mesenchymal transition (EndMT) is widely involved in the occurrence and development of cardiovascular diseases. Although there is no direct evidence, it is very promising as an effective target for the treatment of these diseases. Endothelial cells need to respond to the complex cardiovascular environment through EndMT, but sustained stimuli will cause the imbalance of EndMT. Blocking the signal transduction promoting EndMT is an effective method to control the imbalance of EndMT. In particular, we also discussed the potential role of endothelial cell apoptosis and autophagy in regulating the imbalance of EndMT. In addition, promoting mesenchymal-endothelial transformation (MEndT) is also a method to control the imbalance of EndMT. However, targeting EndMT to treat cardiovascular disease still faces many challenges. By reviewing the research progress of EndMT, we have put forward some insights and translated them into challenges and opportunities for new treatment strategies for cardiovascular diseases.


Assuntos
Doenças Cardiovasculares/patologia , Células Endoteliais/patologia , Transição Epitelial-Mesenquimal , Animais , Apoptose , Autofagia , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Plasticidade Celular , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Fenótipo , Transdução de Sinais
11.
Clin Chim Acta ; 519: 70-75, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33872608

RESUMO

Immunotherapy has become one of the most attraction cancer therapy strategies. The PD-1/PD-L1 pathway plays key roles in immune responses and autoimmunity by regulating T cell activity. Overactivation of this pathway dampens T cell and immune function, which allows tumor cells immune escape. Antibody or inhibitors of PD-1/PD-L1 immune targets have been implicated in clinic anti-cancer therapy and gain great clinic outcoming for their high efficiency. However, recent studies showed that the PD-1/PD-L1 immunotherapy in some tumor patients was found to accelerate T cell-driven inflammatory and the progression of atherosclerotic lesions. This article reviews the research progression of PD-1/PD-L1 in tumors and atherosclerosis, and the possible mechanisms of anti-PD-1/PD-L1 immunotherapy increasing the risk of atherosclerotic lesions.


Assuntos
Aterosclerose , Neoplasias , Antígeno B7-H1 , Humanos , Imunoterapia , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1
12.
Biochem Biophys Res Commun ; 545: 20-26, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33535102

RESUMO

Atherosclerotic cardiovascular disease is the major cause of death worldwide. Low shear stress plays key roles on the initiation and progression of atherosclerosis (As). However, its underlying mechanism remains unclear. In this study, the effect of low shear stress on endothelial mesenchymal transformation (EndMT) and its underlying mechanism were explored. Results showed that in cultured human umbilical vein endothelial cells, low shear stress down-regulated the expression of TET2 and promoted EndMT. Loss of TET2 promoted EndMT with the Wnt/ß-catenin signaling pathway. The enhancement in EndMT induced by low shear stress was attenuated by TET2 overexpression. In apoE-/- mice subjected to carotid artery local ligation, the EndMT and atherosclerotic lesions induced by low shear stress was attenuated by TET2 overexpression. Taken together, low shear stress promoted EndMT through the down-regulation of TET2, indicating that intervention with EndMT or the up-regulation of TET2 might be an alternative strategy for preventing As.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Animais , Aterosclerose/etiologia , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Dioxigenases , Regulação para Baixo , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/fisiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Knockout para ApoE , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , RNA Interferente Pequeno/genética , Estresse Mecânico , Regulação para Cima , Via de Sinalização Wnt
13.
Curr Med Chem ; 28(1): 152-168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32141415

RESUMO

Atherosclerosis is a chronic inflammatory vascular disease. Atherosclerotic cardiovascular disease is the main cause of death in both developed and developing countries. Many pathophysiological factors, including abnormal cholesterol metabolism, vascular inflammatory response, endothelial dysfunction and vascular smooth muscle cell proliferation and apoptosis, contribute to the development of atherosclerosis and the molecular mechanisms underlying the development of atherosclerosis are not fully understood. Ubiquitination is a multistep post-translational protein modification that participates in many important cellular processes. Emerging evidence suggests that ubiquitination plays important roles in the pathogenesis of atherosclerosis in many ways, including regulation of vascular inflammation, endothelial cell and vascular smooth muscle cell function, lipid metabolism and atherosclerotic plaque stability. This review summarizes important contributions of various E3 ligases to the development of atherosclerosis. Targeting ubiquitin E3 ligases may provide a novel strategy for the prevention of the progression of atherosclerosis.


Assuntos
Aterosclerose/enzimologia , Ubiquitina-Proteína Ligases , Ubiquitinação , Células Endoteliais/metabolismo , Humanos , Inflamação , Metabolismo dos Lipídeos , Miócitos de Músculo Liso/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
14.
Free Radic Biol Med ; 162: 582-591, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33248263

RESUMO

Vascular endothelial cell (VEC) inflammation induced by low shear stress plays key roles in the initiation and progression of atherosclerosis (As). Pyroptosis is a form of inflammatory programmed cell death that is critical for As. However, the effect of low shear stress on VEC pyroptosis and the underlying mechanisms were not clear. Here we show that low shear stress promoted VEC pyroptosis and reduced the expression of Ten-Eleven Translocation 2 (TET2) methylcytosine dioxygenase. Loss of TET2 resulted in the upregulation of the expression and activity of mitochondrial respiratory complex II subunit succinate dehydrogenase B (SDHB) by decreasing the recruitment of histone deacetylase 2, independent of DNA demethylation modification. The overexpression of SDHB mediated mitochondrial injury and increased the production of reactive oxygen species (ROS). The administration of ROS scavenger NAC alleviated VEC pyroptosis induced by SDHB overexpression and TET2 shRNA. These findings show that low shear stress induced endothelial cell pyroptosis through the TET2/SDHB/ROS pathway and offer new insights into As.


Assuntos
Aterosclerose , Piroptose , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dioxigenases , Células Endoteliais/metabolismo , Humanos , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Succinato Desidrogenase
15.
Curr Med Chem ; 28(18): 3666-3680, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33200693

RESUMO

Atherosclerosis is a chronic arterial wall illness that forms atherosclerotic plaques within the arteries. Plaque formation and endothelial dysfunction are atherosclerosis' characteristics. It is believed that the occurrence and development of atherosclerosis mainly include endothelial cell damage, lipoprotein deposition, inflammation and fibrous cap formation, but its molecular mechanism has not been elucidated. Therefore, protecting the vascular endothelium from damage is one of the key factors against atherosclerosis. The factors and processes involved in vascular endothelial injury are complex. Finding out the key factors and mechanisms of atherosclerosis caused by vascular endothelial injury is an important target for reversing and preventing atherosclerosis. Changes in cell adhesion are the early characteristics of EndMT, and cell adhesion is related to vascular endothelial injury and atherosclerosis. Recent researches have exhibited that endothelial-mesenchymal transition (EndMT) can urge atherosclerosis' progress, and it is expected that inhibition of EndMT will be an object for anti-atherosclerosis. We speculate whether inhibition of EndMT can become an effective target for reversing atherosclerosis by improving cell adhesion changes and vascular endothelial injury. Studies have shown that H2S has a strong cardiovascular protective effect. As H2S has anti- inflammatory, anti-oxidant, inhibiting foam cell formation, regulating ion channels and enhancing cell adhesion and endothelial functions, the current research on H2S in cardiovascular aspects is increasing, but anti-atherosclerosis's molecular mechanism and the function of H2S in EndMT have not been explicit. In order to explore the mechanism of H2S against atherosclerosis, to find an effective target to reverse atherosclerosis, we sum up the progress of EndMT promoting atherosclerosis, and Hydrogen sulfide's potential anti- EndMT effect is discussed in this review.


Assuntos
Aterosclerose , Placa Aterosclerótica , Aterosclerose/tratamento farmacológico , Células Endoteliais , Transição Epitelial-Mesenquimal , Humanos , Transdução de Sinais
16.
Placenta ; 101: 176-184, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33010604

RESUMO

INTRODUCTION: MiR-124-3p is one of the aberrantly expressed miRNAs in the placentas of patients with preeclampsia (PE), a severe obstetric complication characterised by hypertension and proteinuria. This study aimed to investigate the role of miR-124-3p in the invasion, migration and death of trophoblast cells and explore the potential mechanisms. METHODS: MiR-124-3p expression in placental tissues was compared with that in normal placenta. HTR8/SVneo cells were then transfected with miR-124-3p mimics to examine cellular apoptosis, migration and invasion. Furthermore, the expression of pyroptosis-related molecular NLRP3, Pro-caspase1, caspase1, IL-1ß and GSDMD was examined with Western blot. Dual luciferase reporter assay was performed to confirm that placental growth factor (PLGF) is a direct target of miR-124-3p, and HTR-8/SVneo cells were transfected with small interfering RNA PLGF (siPLGF) to determine whether PLGF knockdown promotes HTR-8/SVneo pyroptosis. Finally, intracellular ROS was diminished with N-acetyl-l-cysteine (NAC) to observe whether the pro-pyroptosis effect of PLGF knockdown is alleviated. RESULTS: Results in this study showed that miR-124-3p expression was remarkably increased in the placenta of patients with PE. Moreover, the transfection of miR-124-3p mimics in trophoblastic cells significantly decreased cell migration and invasion but increased cell apoptosis and the expression of NLRP3, pro-caspase1, caspase1, IL-1ß and GSDMD. Therefore, PLGF was confirmed as a direct target of miR-124-3p. Finally, siPLGF transfection can mimic the effects of miR-124-3p, and NAC can inhibit this effect. CONCLUSION: In summary, miR-124-3p is upregulated in PE, and in vitro functional analysis revealed that this mRNA inhibits trophoblast invasion and migration but promotes cell pyroptosis partly via the PLGF-ROS pathway.


Assuntos
MicroRNAs/metabolismo , Fator de Crescimento Placentário/metabolismo , Pré-Eclâmpsia/metabolismo , Piroptose , Trofoblastos/fisiologia , Adulto , Estudos de Casos e Controles , Linhagem Celular , Feminino , Humanos , Pré-Eclâmpsia/etiologia , Gravidez
17.
DNA Cell Biol ; 39(4): 661-670, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32101022

RESUMO

Fibroblast growth factor 21 (FGF21) is a hormone-like member of the FGF family that is associated with cell death in atherosclerosis. However, its underlying mechanisms remain unclear. In this study, the effect of FGF21 on endothelial cell pyroptosis and its potential mechanisms were investigated. Results showed that FGF21 inhibits oxidized low-density lipoprotein (ox-LDL)-induced pyroptosis and related molecular expression in human umbilical vein endothelial cells (HUVECs). Mitochondrial function was damaged by ox-LDL and restored by FGF21. A mechanism proved that ubiquinol cytochrome c reductase core protein I (UQCRC1) was downregulated by ox-LDL and upregulated by FGF21. Further, the silencing of UQCRC1 aggravated HUVEC pyroptosis and impaired mitochondrial function and reactive oxygen species (ROS) production. Moreover, Tet methylcytosine dioxygenase (TET2) was involved in the regulation of UQCRC1 expression and pyroptosis. In summary, FGF21 inhibited ox-LDL-induced HUVEC pyroptosis through the TET2-UQCRC1-ROS pathway.


Assuntos
Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Lipoproteínas LDL/metabolismo , Piroptose/fisiologia , Aterosclerose/patologia , Sobrevivência Celular , Células Cultivadas , Proteínas de Ligação a DNA/metabolismo , Dioxigenases , Complexo III da Cadeia de Transporte de Elétrons/genética , Fatores de Crescimento de Fibroblastos/genética , Humanos , Potencial da Membrana Mitocondrial/fisiologia , Mitocôndrias/metabolismo , Estresse Oxidativo/fisiologia , Proteínas Proto-Oncogênicas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
18.
Cardiovasc Drugs Ther ; 34(1): 113-121, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32090295

RESUMO

Hydrogen sulfide (H2S), a novel gaseous signaling molecule, is a vital physiological signal in mammals. H2S protects the cardiovascular system via modulation of vasodilation, vascular remodeling, and inhibition of vascular calcification, and also has anti-atherosclerosis properties. Autophagy is a lysosomal-mediated intracellular degradation mechanism for excessive or abnormal proteins and lipids. The contribution of autophagy to normal and disease-state cell physiology is extremely complicated. Autophagy acts as a double-edged sword in the cardiovascular system. It can defend against damage to cells caused by environmental changes and it can also induce active cell death under certain conditions. In recent years, accumulating evidence indicates that H2S can up- or downregulate autophagy in many pathological processes, thereby switching from a harmful to a beneficial role. In this review, we summarize progress on understanding the mechanism by which H2S regulates autophagy in cardiovascular disease. We also discuss a H2S switch phenomenon that regulates autophagy and provides protection in cardiovascular diseases.


Assuntos
Autofagia , Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/metabolismo , Sulfeto de Hidrogênio/metabolismo , Animais , Apoptose , Autofagia/efeitos dos fármacos , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/patologia , Sistema Cardiovascular/fisiopatologia , Humanos , Sulfeto de Hidrogênio/uso terapêutico , Transdução de Sinais
19.
J Cell Physiol ; 235(10): 6582-6591, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32012263

RESUMO

Trimethylamine N-oxide (TMAO) is produced from the phosphatidylcholine metabolism of gut flora and acts as a risk factor of cardiovascular disease. However, the underlying mechanisms for its proatherogenic action remain unclear. This study aimed to observe the effect of TMAO on endothelial cell pyroptosis and explore the underlying mechanisms. Our results showed that TMAO promoted the progression of atherosclerotic lesions in apolipoprotein E-deficient (apoE-/- ) mice fed a high-fat diet. Pyroptosis and succinate dehydrogenase complex subunit B (SDHB) upregulation were detected in the vascular endothelial cells of apoE-/- mice and in cultured human umbilical vein endothelial cells (HUVECs) treated with TMAO. Overexpression of SDHB in HUVECs enhanced pyroptosis and impaired mitochondria and high reactive oxygen species (ROS) level. Pyroptosis in the SDHB overexpression of endothelial cells was inhibited by the ROS scavenger NAC. In summary, TMAO promotes vascular endothelial cell pyroptosis via ROS induced through SDHB upregulation, thereby contributing to the progression of atherosclerotic lesions.


Assuntos
Apolipoproteínas E/metabolismo , Aterosclerose/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Metilaminas/farmacologia , Piroptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Succinato Desidrogenase/metabolismo , Animais , Células Cultivadas , Humanos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
20.
DNA Cell Biol ; 39(1): 8-15, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31825254

RESUMO

Atherosclerosis is a major disease that seriously harms human health and is known as the "number one killer" in developed countries and the leading cause of death worldwide. Glutamine is the most abundant nonessential amino acid in the human blood that has multifaceted effects on the body. Recent studies showed that glutamine is negatively corrected with the progression of atherosclerotic lesions. In this review, we focused on the relationship of glutamine with macrophage polarization, nitrification stress, oxidative stress injury, myocardial ischemia-reperfusion injury, and therapeutic angiogenesis to review its roles in atherosclerotic cardiovascular disease.


Assuntos
Aterosclerose/sangue , Doenças Cardiovasculares/sangue , Glutamina/sangue , Ativação de Macrófagos , Estresse Oxidativo , Animais , Aterosclerose/patologia , Doenças Cardiovasculares/patologia , Progressão da Doença , Humanos , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Neovascularização Patológica/sangue , Neovascularização Patológica/fisiopatologia
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