Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.830
Filtrar
1.
Prog Cardiovasc Dis ; 84: 43-50, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38734044

RESUMO

Atherosclerotic cardiovascular (CV) disease (ASCVD) prevention encompasses interventions across the lifecourse: from primordial to primary and secondary prevention. Primordial prevention begins in childhood and involves the promotion of ideal CV health (CVH) via optimizing physical activity, body mass index, blood glucose levels, total cholesterol levels, blood pressure, and sleep while minimizing tobacco use. Primary and secondary prevention of ASCVD thereafter centers around mitigating ASCVD risk factors via medical therapy and lifestyle interventions. Disparities in optimal preventive efforts exist among historically marginalized groups in each of these three prongs of ASCVD prevention. Children and adults with a high burden of social determinants of health also face inequity in preventive measures. Inadequate screening, risk factor management and prescription of preventive therapeutics permeate the care of certain groups, especially women, Black, and Hispanic individuals in the United States. Beyond this, individuals belonging to historically marginalized groups also are much more likely to experience other ASCVD risk-enhancing factors, placing them at higher risk for ASCVD over their lifetime. These disparities translate to worse outcomes, with higher rates of ASCVD and CV mortality among these groups. Possible solutions to promoting equity involve community-based youth lifestyle interventions, improved risk-factor screening, and increasing accessibility to healthcare resources and novel preventive diagnostics and therapeutics.


Assuntos
Aterosclerose , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Humanos , Disparidades em Assistência à Saúde/etnologia , Aterosclerose/prevenção & controle , Aterosclerose/epidemiologia , Aterosclerose/terapia , Aterosclerose/etnologia , Determinantes Sociais da Saúde , Medição de Risco , Prevenção Primária , Fatores de Risco de Doenças Cardíacas , Prevenção Secundária/métodos , Comportamento de Redução do Risco , Fatores de Risco , Feminino , Acessibilidade aos Serviços de Saúde , Serviços Preventivos de Saúde , Masculino , Estilo de Vida Saudável , Estados Unidos/epidemiologia
2.
PLoS One ; 19(5): e0300745, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38696494

RESUMO

OBJECTIVE: This study aimed to investigate the impacts of continuity of care (COC) between patients and multiple providers, i.e., doctors and community pharmacists, on clinical and economic outcomes. METHODS: This is a retrospective cohort study and analyzed Korean national claims data for ambulatory care setting between 2007 and 2018. Patients with dyslipidemia newly diagnosed in 2008 were identified. COC between providers and patients was computed using the continuity of care index (COCI). Based on COCIs, the study patients were allocated to four groups: HM/HP, HM/LP, LM/HP, and LM/LP. Each symbol represents H for high, L for low, M for doctor, and P for pharmacist. The primary study outcome was the incidence of atherosclerotic cardiovascular disease (ASCVD). RESULTS: 126,710 patients were included. Percentages of patients in the four study groups were as follows: HM/HP 35%, HM/LP 19%, LM/HP 12%, and LM/LP 34%. During the seven-year outcome period, 8,337 patients (6.6%) developed an ASCVD, and percentages in the study groups were as follows; HM/HP 6.2%, HM/LP 6.3%, LM/HP 6.8%, and LM/LP 7.1%. After adjusting for confounding covariates, only the LM/LP group had a significantly higher risk of ASCVD than the reference group, HM/HP (aHR = 1.16 [95% confidence interval = 1.10~1.22]). The risk of inappropriate medication adherence gradually increased 1.03-fold in the HM/LP group, 1.67-fold in the LM/HP, and 2.26-fold in the LM/LP group versus the HM/HP group after adjusting for covariates. Disease-related costs were lower in the HM/HP and LM/HP groups. CONCLUSIONS: The study shows that patients with high relational care continuity with doctors and pharmacists achieved better clinical results and utilized health care less, resulting in reduced expenses. Further exploration for the group that exhibits an ongoing relationship solely with pharmacists is warranted.


Assuntos
Continuidade da Assistência ao Paciente , Dislipidemias , Humanos , Masculino , Feminino , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , República da Coreia/epidemiologia , Farmacêuticos , Idoso , Adulto , Médicos , Aterosclerose/epidemiologia , Aterosclerose/terapia , Estudos de Coortes
3.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732155

RESUMO

The goal of this Special Issue was to collect original pieces as well as state-of-the-art review articles from scientists and research groups with specific interests in atherosclerosis research [...].


Assuntos
Aterosclerose , Humanos , Aterosclerose/metabolismo , Aterosclerose/terapia , Aterosclerose/genética , Animais , Cardiologia/métodos
4.
Sci Rep ; 14(1): 7835, 2024 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570516

RESUMO

Cardiovascular risk increases during the aging process in women with atherosclerosis and exercise training is a strategy for management of cardiac risks in at-risk populations. Therefore, the aims of this study were to evaluate: (1) the influence of the aging process on cardiac function, hemodynamics, cardiovascular autonomic modulation, and baroreflex sensitivity in females with atherosclerosis at the onset of reproductive senescence; and (2) the impact of exercise training on age-related dysfunctions in this model. Eighteen Apolipoprotein-E knockout female mice were divided equally into young (Y), middle-aged (MA), and trained middle-aged (MAT). Echocardiographic exams were performed to verify cardiac morphology and function. Cannulation for direct recording of blood pressure and heart rate, and analysis of cardiovascular autonomic modulation, baroreflex sensitivity were performed. The MA had lower cardiac diastolic function (E'/A' ratio), and higher aortic thickness, heart rate and mean arterial pressure, lower heart rate variability and baroreflex sensitivity compared with Y. There were no differences between Y and MAT in these parameters. Positive correlation coefficients were found between aortic wall thickness with hemodynamics data. The aging process causes a series of deleterious effects such as hemodynamic overload and dysautonomia in female with atherosclerosis. Exercise training was effective in mitigating aged-related dysfunctions.


Assuntos
Aterosclerose , Doenças do Sistema Nervoso Autônomo , Sistema Cardiovascular , Humanos , Pessoa de Meia-Idade , Feminino , Camundongos , Animais , Idoso , Coração , Hemodinâmica , Pressão Sanguínea/fisiologia , Frequência Cardíaca , Aterosclerose/terapia
5.
Zhen Ci Yan Jiu ; 49(4): 376-383, 2024 Apr 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38649205

RESUMO

OBJECTIVES: To observe the effects of moxibustion on blood lipid metabolism, pathological morphology of thoracic aorta, and the expression of silent information regulator 1 (SIRT1) and forkhead box transcription factor O3a (FOXO3a) in ApoE-/- atherosclerosis (AS) mice, so as to explore the potential mechanism of moxibustion in preventing and treating AS. METHODS: Ten C57BL/6J mice were fed a normal diet as the control group, and 30 ApoE-/- mice were fed a high-fat diet to establish the AS model, which were randomly divided into the model group, simvastatin group, and moxibustion group, with 10 mice in each group. From the first day of modeling, mice in the moxibustion group received mild moxibustion treatment at "Shenque"(CV8), "Yinlingquan"(SP9), bilateral "Neiguan"(PC6) and "Xuehai"(SP10) for 30 min per time;the mice in the simvastatin group were given simvastatin orally (2.5 mg·kg-1·d-1), with both treatments given once daily, 5 times a week, with a total intervention period of 12 weeks. The body weight and general condition of the mice were observed and recorded during the intervention period. After the intervention, the contents of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automated biochemistry analyzer. Hematoxylin eosin (HE) staining was used to observe the pathological morphology of the thoracic aorta. ELISA was used to measure the contents of serum oxidized low-density lipoprotein (ox-LDL) and superoxide dismutase (SOD) activity. Western blot and real-time fluorescent quantitative PCR analysis were used to detect the expression levels of SIRT1 and FOXO3a protein and mRNA in the thoracic aorta. RESULTS: Compared with the control group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of the model group mice were significantly increased(P<0.05, P<0.01), while the HDL-C contents, SOD activity, and the expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly decreased(P<0.05, P<0.01). HE staining showed thickening of the aortic intima, endothelial cell degeneration, swelling, and shedding. Compared with the model group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of mice in the simvastatin group and moxibustion group were significantly decreased(P<0.01), while the serum SOD activity, expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly increased(P<0.01). The HDL-C contents were significantly increased in the simvastatin group(P<0.05). The thoracic aortic structure was more intact in both groups, with a more regular lumen and orderly arrangement of the elastic membrane in the media, and a slight amount of endothelial cell degeneration and swelling in the intima. There was no significant difference in the evaluated indexes between the moxibustion group and the simvastatin group and the pathological changes in the thoracic aorta were similar between the two groups. CONCLUSIONS: Moxibustion can reduce the body weight of AS model mice, regulate lipid levels, repair vascular intima, and alleviate endothelial damage. Its mechanism of action may be related to the regulation of the SIRT1/FOXO3a signaling pathway to improve oxidative damage.


Assuntos
Apolipoproteínas E , Aterosclerose , Proteína Forkhead Box O3 , Moxibustão , Sirtuína 1 , Animais , Humanos , Masculino , Camundongos , Pontos de Acupuntura , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerose/metabolismo , Aterosclerose/genética , Aterosclerose/terapia , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais , Sirtuína 1/metabolismo , Sirtuína 1/genética , Triglicerídeos/sangue , Triglicerídeos/metabolismo
6.
Prog Mol Biol Transl Sci ; 204: 1-43, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38458734

RESUMO

Atherosclerosis represents a pathological state that affects the arterial system of the organism. This chronic, progressive condition is typified by the accumulation of atheroma within arterial walls. Modulation of RNA molecules through RNA-based therapies has expanded the range of therapeutic options available for neurodegenerative diseases, infectious diseases, cancer, and, more recently, cardiovascular disease (CVD). Presently, microRNAs and small interfering RNAs (siRNAs) are the most widely employed therapeutic strategies for targeting RNA molecules, and for regulating gene expression and protein production. Nevertheless, for these agents to be developed into effective medications, various obstacles must be overcome, including inadequate binding affinity, instability, challenges of delivering to the tissues, immunogenicity, and off-target toxicity. In this comprehensive review, we discuss in detail the current state of RNA interference (RNAi)-based therapies.


Assuntos
Aterosclerose , MicroRNAs , Neoplasias , Humanos , Interferência de RNA , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Interferente Pequeno/uso terapêutico , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Neoplasias/terapia , Aterosclerose/terapia , Aterosclerose/tratamento farmacológico
7.
Med Clin North Am ; 108(3): 419-425, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38548454

RESUMO

Chronic coronary heart disease encompasses a broad spectrum of disorders that range in severity from trivial to imminently life-threatening. The primary care physician encounters coronary disease at all stages. The number of available diagnostic and therapeutic options for evaluating and treating coronary disease is vast, presenting a complex selection strategy challenge when making choices for the individual patient. The primary care physician is responsible to tailor evaluation and management strategies to each individual patient based on his/her particular disease characteristics. There are many categories of diagnostic studies and therapeutic interventions that have been shown at the population level in clinical trials to improve patient outcomes. Blindly applying the findings of all demonstrated studies and therapies to a patient with coronary disease would saddle him/her with an unsustainable burden of diagnostic tests and therapies. The core principle of the approach outlined in this article is to tailor diagnostic and therapeutic choices to the operative pathophysiology that drives a particular patient's disorder. This introductory article is intended to provide a conceptual framework for studying and applying the specialized topics discussed in the articles that follow.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Doença da Artéria Coronariana , Isquemia Miocárdica , Humanos , Feminino , Masculino , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/terapia , Isquemia Miocárdica/diagnóstico , Aterosclerose/diagnóstico , Aterosclerose/terapia , Doença Crônica
8.
Ageing Res Rev ; 96: 102273, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492810

RESUMO

Cardiovascular disease is currently the largest cause of mortality and disability globally, surpassing communicable diseases, and atherosclerosis is the main contributor to this epidemic. Aging is intimately linked to atherosclerosis development and progression, however, the mechanism of aging in atherosclerosis is not well known. To emphasize the significant research on the involvement of senescent cells in atherosclerosis, we begin by outlining compelling evidence that indicates various types of senescent cells and SASP factors linked to atherosclerotic phenotypes. We subsequently provide a comprehensive summary of the existing knowledge, shedding light on the intricate mechanisms through which cellular senescence contributes to the pathogenesis of atherosclerosis. Further, we cover that senescence can be identified by both structural changes and several senescence-associated biomarkers. Finally, we discuss that preventing accelerated cellular senescence represents an important therapeutic potential, as permanent changes may occur in advanced atherosclerosis. Together, the review summarizes the relationship between cellular senescence and atherosclerosis, and inspects the molecular knowledge, and potential clinical significance of senescent cells in developing senescent-based therapy, thus providing crucial insights into their biology and potential therapeutic exploration.


Assuntos
Aterosclerose , Senescência Celular , Humanos , Envelhecimento , Biomarcadores , Fenótipo , Aterosclerose/terapia
9.
Curr Opin Cardiol ; 39(4): 292-299, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38547148

RESUMO

PURPOSE OF REVIEW: RNA interference (RNAi)-based therapies that target specific gene products have impacted clinical medicine with 16 FDA approved drugs. RNAi therapy focused on reducing plasma lipoprotein(a) [Lp(a)] levels are under evaluation. RECENT FINDINGS: RNAi-based therapies have made significant progress over the past 2 decades and currently consist of antisense oligonucleotides (ASO) and small interfering RNA (siRNA). Chemical modification of the RNA backbone and conjugation of siRNA enables efficient gene silencing in hepatocytes allowing development of effective cholesterol lowering therapies. Multiple lines of evidence suggest a causative role for Lp(a) in atherosclerotic cardiovascular disease, and recent analyses indicate that Lp(a) is more atherogenic than low density lipoprotein- cholesterol (LDL-C). These findings have led to the 'Lp(a) hypothesis' that lowering Lp(a) may significantly improve cardiovascular outcomes. Four RNAi-based drugs have completed early phase clinical trials demonstrating >80% reduction in plasma Lp(a) levels. Phase 3 clinical trials examining clinical outcomes with these agents are currently underway. SUMMARY: Currently, four RNAi-based drugs have been shown to be effective in significantly lowering plasma Lp(a) levels. Clinical outcome data from phase 3 trials will evaluate the Lp(a) hypothesis.


Assuntos
Lipoproteína(a) , Interferência de RNA , RNA Interferente Pequeno , Humanos , Lipoproteína(a)/sangue , RNA Interferente Pequeno/uso terapêutico , Oligonucleotídeos Antissenso/uso terapêutico , Aterosclerose/terapia , Aterosclerose/tratamento farmacológico , Terapêutica com RNAi/métodos
10.
Cell Res ; 34(6): 407-427, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38491170

RESUMO

Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1+ T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without Fc-binding capability. Our analysis shows that anti-PD-1 mAb with Fc-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without Fc-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans.


Assuntos
Aterosclerose , Receptor de Morte Celular Programada 1 , Linfócitos T , Humanos , Aterosclerose/imunologia , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Aterosclerose/terapia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inflamação/patologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/farmacologia , Feminino , Masculino , Estudos Retrospectivos , Receptores de IgG/metabolismo , Placa Aterosclerótica/patologia , Placa Aterosclerótica/imunologia , Placa Aterosclerótica/terapia , Placa Aterosclerótica/tratamento farmacológico , Pessoa de Meia-Idade
11.
Int Immunopharmacol ; 132: 111856, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38537537

RESUMO

BACKGROUND AND AIMS: Inflammation and atherosclerosis (AS) are closely associated to Secreted Protein Acidic and Rich in Cysteine (SPARC) and its related factors. This study attempted to define the role and the potential mechanism of SPARC and its related factors in ameliorating hyperlipidemia and AS by aerobic exercise intervention. METHODS: The AS rat model was established with a high-fat diet plus vitamin D3 intraperitoneal injection. Treadmill exercises training (5 days/week at 14 m/min for 60 min/day) for 6 weeks was carried out for AS rat intervention method. Western blotting and qRT-PCR were used to analyze the mRNA and protein expression of SPARC and its related factors, respectively. H&E staining was applied to evaluate the morphological changes and inflammation damage. Von Kossa staining was used to measure the degree of vascular calcification. Fluorescence immunohistochemistry staining was used to detect the expression and distribution of SPARC signal molecules. RESULTS: SPARC was highly expressed and co-localization with the smooth muscle marker α-SMC in the AS rat. And its downstream factors, NF-κB, Caspase-1, IL-1ß and IL-18 were upregulated (P < 0.05 or P < 0.01), FNDC5 expression was downregulated in AS rat model. However, slight declined body weight, delayed AS progression, decreased hyperlipidemia and favorable morphology of skeletal muscle and blood vessels have been detected in AS rat with aerobic exercise intervention. Moreover, the expression of SPARC and its downstream factors were decreased (P < 0.05 or P < 0.01), while elevated the expression of FNDC5 (P < 0.01) was observed after aerobic exercise intervention. CONCLUSIONS: This study suggested that aerobic exercise ameliorated hyperlipidemia and AS by effectively inhibiting SPARC signal, and vascular smooth muscle cells may contribute greatly to the protection of AS.


Assuntos
Aterosclerose , Dieta Hiperlipídica , Osteonectina , Condicionamento Físico Animal , Ratos Sprague-Dawley , Animais , Osteonectina/metabolismo , Osteonectina/genética , Aterosclerose/terapia , Aterosclerose/metabolismo , Masculino , Ratos , Transdução de Sinais , Modelos Animais de Doenças , Hiperlipidemias/terapia , Hiperlipidemias/metabolismo , Colecalciferol/metabolismo
12.
Zhongguo Zhen Jiu ; 44(2): 169-174, 2024 Feb 12.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38373762

RESUMO

OBJECTIVES: To observe the effects of Lizhong Tongmai acupuncture (acupuncture for regulating middle jiao and promoting meridians) on trimethylamine-N-oxide (TMAO), CD36 expression, and cholesterol deposition in atherosclerotic (AS) mice, exploring potential mechanism of electroacupuncture (EA) in treating AS. METHODS: A total of 31 male SPF-grade C57BL/6J ApoE-/- mice were fed with high-fat diet for 8 weeks to establish AS model. After successful modeling, the remaining 30 mice were randomly divided into a model group, a medication group, and an EA group, with 10 mice in each group. An additional 10 normal mice of the same strain were selected as a blank group. The mice in the blank group and the model group received no intervention. The mice in the medication group were treated with intragastric administration of atorvastatin calcium. The mice in the EA group were treated with EA at "Neiguan" (PC 6), "Tianshu" (ST 25) and "Zusanli" (ST 36). The same-side "Neiguan" (PC 6) and "Zusanli" (ST 36), "Tianshu" (ST 25) and the tail of the mice were connected to the EA apparatus, with disperse-dense wave, a frequency of 2 Hz/15 Hz, and a current intensity of 0.3 mA for 10 min per session. Acupuncture was performed unilaterally per session, alternating between the left and right sides, with a frequency of once every other day. After intervention, HE staining was used to observe the pathological morphology of the aorta. Microplate assays were conducted to measure triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels in serum. Ultra high performance liquid chromatography-mass spectrometry technique (UPLC-MS) was employed to detect TMAO level in plasma. Western blot was performed to assess CD36 protein expression level in the aorta. Microanalysis was used to measure cholesterol ester (CE) level in the aorta and the CE/TC ratio was calculated. RESULTS: Compared with the blank group, the mice in the model group exhibited significant pathological changes of atherosclerosis, serum TG, TC, LDL-C levels were increased (P<0.01), and HDL-C level was decreased (P<0.01); the plasma TMAO level, aortic CE level, and the CE/TC ratio were increased (P<0.01), along with elevated CD36 protein expression level in the aorta (P<0.01). Compared with the model group, the mice in the medication group and the EA group showed improvements in aortic pathology, serum TG, TC, LDL-C levels were reduced, HDL-C levels were increased (P<0.05); plasma TMAO levels, aortic CE levels, and the CE/TC ratio were decreased (P<0.01), and CD36 protein expression levels were lowered (P<0.05). The serum TG and TC levels in the EA group were higher than those in the medication group (P<0.05). CONCLUSIONS: The Lizhong Tongmai acupuncture can ameliorate aortic pathological changes, regulate blood lipid levels, reduce plasma TMAO level, inhibit CD36 protein expression in the aorta, and decrease cholesterol deposition. These effects may contribute to the therapeutic mechanism of EA in treating AS.


Assuntos
Aterosclerose , Eletroacupuntura , Metilaminas , Masculino , Camundongos , Animais , Antígenos CD36/genética , LDL-Colesterol/metabolismo , Cromatografia Líquida , Camundongos Endogâmicos C57BL , Pontos de Acupuntura , Camundongos Knockout para ApoE , Espectrometria de Massas em Tandem , Aterosclerose/genética , Aterosclerose/terapia , Aterosclerose/metabolismo
13.
Sci Rep ; 14(1): 2762, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307884

RESUMO

Lipoprotein apheresis (LA) is a therapeutic option for hyperlipoproteinemia(a) (hyper-Lp(a)) and atherosclerotic cardiovascular disease (ASCVD). LA improves blood rheology, reduces oxidative stress parameters and improves endothelial function. The underlying molecular mechanisms of LA beneficial effects are unknown, but it has been suggested that LA exhibits multiple activities beyond simply removing lipoproteins. We hypothesized that LA removes not only lipoproteins, but also extracellular vesicles (EVs). To test this hypothesis, we performed a prospective study in 22 patients undergoing LA for hyper-Lp(a) and ASCVD. Different EVs subtypes were measured before and directly after LA, and after 7 days. We used calibrated flow cytometry to detect total particle concentration (diameter > ~ 100 nm), total lipoproteins concentration (diameter > 200 nm, RI > 1.51), total EV concentration (diameter > 200 nm, RI < 1.41), concentrations of EVs derived from erythrocytes (CD235a+; diameter > 200 nm, RI < 1.41), leukocytes (CD45+; diameter > 200 nm, RI < 1.41) and platelets (CD61+, PEVs; diameter > 200 nm, RI < 1.41). LA reduced the concentrations of all investigated EVs subtypes and lipoproteins. Lp(a) concentration was lowered by 64.5% [(58% - 71%); p < 0.001]. Plasma concentrations of EVs > 200 nm in diameter derived from platelets (CD61 +), leukocytes (CD45+) and erythrocytes (CD235a+) decreased after single LA procedure by 42.7% [(12.8-54.7); p = 0.005], 42.6% [(29.7-54.1); p = 0.030] and 26.7% [(1.0-62.7); p = 0.018], respectively, compared to baseline. All EV subtypes returned to the baseline concentrations in blood plasma after 7 days. To conclude, LA removes not only Lp(a), but also cell-derived EVs, which may contribute to LA beneficial effects.


Assuntos
Aterosclerose , Remoção de Componentes Sanguíneos , Vesículas Extracelulares , Hiperlipoproteinemias , Humanos , Estudos Prospectivos , Lipoproteína(a) , Remoção de Componentes Sanguíneos/métodos , Aterosclerose/terapia
14.
Adv Sci (Weinh) ; 11(17): e2308298, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38368274

RESUMO

Atherosclerosis, a multifaceted chronic inflammatory disease, has a profound impact on cardiovascular health. However, the critical limitations of atherosclerosis management include the delayed detection of advanced stages, the intricate assessment of plaque stability, and the absence of efficacious therapeutic strategies. Nanotheranostic based on nanotechnology offers a novel paradigm for addressing these challenges by amalgamating advanced imaging capabilities with targeted therapeutic interventions. Meanwhile, iron oxide nanoparticles have emerged as compelling candidates for theranostic applications in atherosclerosis due to their magnetic resonance imaging capability and biosafety. This review delineates the current state and prospects of iron oxide nanoparticle-based nanotheranostics in the realm of atherosclerosis, including pivotal aspects of atherosclerosis development, the pertinent targeting strategies involved in disease pathogenesis, and the diagnostic and therapeutic roles of iron oxide nanoparticles. Furthermore, this review provides a comprehensive overview of theranostic nanomedicine approaches employing iron oxide nanoparticles, encompassing chemical therapy, physical stimulation therapy, and biological therapy. Finally, this review proposes and discusses the challenges and prospects associated with translating these innovative strategies into clinically viable anti-atherosclerosis interventions. In conclusion, this review offers new insights into the future of atherosclerosis theranostic, showcasing the remarkable potential of iron oxide-based nanoparticles as versatile tools in the battle against atherosclerosis.


Assuntos
Aterosclerose , Nanopartículas Magnéticas de Óxido de Ferro , Nanomedicina Teranóstica , Nanomedicina Teranóstica/métodos , Aterosclerose/terapia , Humanos , Nanopartículas Magnéticas de Óxido de Ferro/química , Animais , Compostos Férricos/química , Compostos Férricos/uso terapêutico , Nanopartículas/uso terapêutico , Nanopartículas/química
15.
ACS Biomater Sci Eng ; 10(3): 1190-1206, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38343186

RESUMO

Cardiovascular disease poses a significant threat to human health in today's society. A major contributor to cardiovascular disease is atherosclerosis (AS). The development of plaque in the affected areas involves a complex pathological environment, and the disease progresses rapidly. Nanotechnology, combined with emerging diagnostic and treatment methods, offers the potential for the management of this condition. This paper presents the latest advancements in environment-intelligent responsive controlled-release nanoparticles designed specifically for the pathological environment of AS, which includes characteristics such as low pH, high reactive oxygen species levels, high shear stress, and multienzymes. Additionally, the paper summarizes the applications and features of nanotechnology in interventional therapy for AS, including percutaneous transluminal coronary angioplasty and drug-eluting stents. Furthermore, the application of nanotechnology in the diagnosis of AS shows promising real-time, accurate, and continuous effects. Lastly, the paper explores the future prospects of nanotechnology, highlighting the tremendous potential in the diagnosis and treatment of atherosclerotic diseases, especially with the ongoing development in nano gas, quantum dots, and Metal-Organic Frameworks materials.


Assuntos
Angioplastia Coronária com Balão , Aterosclerose , Doenças Cardiovasculares , Stents Farmacológicos , Nanopartículas , Humanos , Aterosclerose/diagnóstico , Aterosclerose/terapia , Aterosclerose/patologia , Nanopartículas/uso terapêutico
17.
Transpl Immunol ; 83: 102000, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38262540

RESUMO

Cardiovascular diseases (CVD) are one of the most challenging diseases and many factors have been demonstrated to affect their pathogenesis. One of the major factors that affect CVDs, especially atherosclerosis, is the gut microbiota (GM). Genetics play a key role in linking CVDs with GM, in addition to some environmental factors which can be either beneficial or harmful. The interplay between GM and CVDs is complex due to the numerous mechanisms through which microbial components and their metabolites can influence CVDs. Within this interplay, the immune system plays a major role, mainly based on the immunomodulatory effects of microbial dysbiosis and its resulting metabolites. The resulting modulation of chronic inflammatory processes was found to reduce the severity of CVDs and to maintain cardiovascular health. To better understand the specific roles of GM-related metabolites in this interplay, this review presents an updated perspective on gut metabolites related effects on the cardiovascular system, highlighting the possible benefits of probiotics in therapeutic strategies.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Microbioma Gastrointestinal , Probióticos , Humanos , Doenças Cardiovasculares/complicações , Probióticos/uso terapêutico , Inflamação , Aterosclerose/etiologia , Aterosclerose/terapia
18.
Curr Cardiol Rev ; 20(2): 39-49, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38288833

RESUMO

Triglycerides have long been recognized as a cardiovascular disease risk factor. However, their precise role in atherosclerosis and potential utility as a therapeutic target remains debated topics. This review aims to shed light on these aspects by exploring the complex relationship between triglycerides and atherosclerosis from pathophysiological and pharmacological perspectives. Triglycerides, primarily carried by chylomicrons and very low-density lipoproteins, play an essential role in energy storage and utilization. Dysregulation of triglyceride homeostasis and triglyceride- rich lipoproteins metabolism often leads to hypertriglyceridemia and subsequently increases atherosclerosis risk. Triglyceride-rich lipoproteins remnants interact with arterial wall endothelial cells, get retained in the subendothelial space, and elicit inflammatory responses, thereby accelerating atherogenesis. Despite the clear association between high triglyceride levels and increased cardiovascular disease risk, intervention trials targeting triglyceride reduction have produced mixed results. We discuss a range of triglyceride-lowering agents, from fibrates to omega-3 fatty acids, with a focus on their mechanism of action, efficacy, and major clinical trial outcomes. Notably, the role of newer agents, such as angiopoietin-like protein 3 and apolipoprotein C3 inhibitors, is also explored. We highlight the challenges and controversies, including the ongoing debate on the causal role of triglyceride in atherosclerosis and the discordant outcomes of recent clinical trials. The potential confounding effects of associated risk factors, such as elevated apolipoprotein B, insulin resistance, and metabolic syndrome, are considered. In conclusion, this review underscores the importance of a nuanced approach to understanding the role of triglycerides in atherosclerosis and their potential as a therapeutic target. Further research is needed to unravel the complex interplay between triglycerides, triglyceride-rich lipoproteins, and associated factors in atherosclerosis pathogenesis and refine triglyceride-targeted therapeutic strategies.


Assuntos
Aterosclerose , Hipolipemiantes , Triglicerídeos , Humanos , Aterosclerose/terapia , Aterosclerose/metabolismo , Aterosclerose/etiologia , Triglicerídeos/metabolismo , Hipolipemiantes/uso terapêutico , Hipertrigliceridemia/complicações , Hipertrigliceridemia/terapia , Hipertrigliceridemia/metabolismo
19.
Adv Mater ; 36(19): e2312102, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38289723

RESUMO

The atherosclerotic vulnerable plaque is characterized by the foamy macrophage burden, involving impaired cholesterol efflux and deficient efferocytosis. Correspondingly, piezocatalytic therapy is an emerging solution for eliminating the foamy macrophage burden with satisfactory spatiotemporal controllability and deep penetration depth. Herein, a biomimetic Trojan horse (Au-ZnO@MM) is engineered by coating the macrophage membrane (MM) onto the surface of a rod-like Au-ZnO Schottky Junction to effectively relieve the atherosclerotic progression. These Trojan horses with the coating of MM are actively transported into subsistent foamy macrophages and generate abundant reactive oxygen species (ROS) via ultrasound-activated piezocatalysis. ROS-initiated autophagy and mitochondrial dysfunction induce substantial cell apoptosis, alleviating the burden of subsistent foamy macrophages. The resulting apoptotic fragments further significantly facilitate cholesterol excretion and trigger efferocytosis of intraplaque fresh macrophages. Ultimately, the biomimetic Au-ZnO@MM piezocatalyst not only inhibits the foaming capacity of macrophages, but also improves the function of removing cell debris, which can stabilize atherosclerotic vulnerable plaque. Meanwhile, the plasmon resonance effect of integrated gold nanoparticles enables favorable photoacoustic molecular imaging for real-time image-guided atherosclerotic therapy. This proposed biomimetic Trojan horse strategy provides the paradigm of employing ultrasound-activated piezocatalytic methodology for enhanced atherosclerotic theranostics.


Assuntos
Aterosclerose , Materiais Biomiméticos , Ouro , Espécies Reativas de Oxigênio , Óxido de Zinco , Animais , Aterosclerose/terapia , Aterosclerose/diagnóstico por imagem , Aterosclerose/metabolismo , Ouro/química , Materiais Biomiméticos/química , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Óxido de Zinco/química , Células RAW 264.7 , Macrófagos/metabolismo , Humanos , Nanopartículas Metálicas/química , Catálise , Biomimética/métodos , Apoptose/efeitos dos fármacos , Placa Aterosclerótica/patologia
20.
Mol Cell Biochem ; 479(4): 779-791, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37178375

RESUMO

Cardiovascular disease (CVD) has a high incidence and low cure rate worldwide, and atherosclerosis (AS) is the main factor inducing cardiovascular disease, of which lipid deposition in the vessel wall is the main marker of AS. Currently, although statins can be used to lower lipids and low-density lipoprotein (LDL) in AS, the cure rate for AS remains low. Therefore, there is an urgent need to develop new therapeutic approaches, and stem cells are now widely studied, while stem cells are a class of cell types that always maintain the ability to differentiate and can differentiate to form other cells and tissues, and stem cell transplantation techniques have shown efficacy in the treatment of other diseases. With the establishment of cellular therapies and continued research in stem cell technology, stem cells are also being used to address the problem of AS. In this paper, we focus on recent research advances in stem cell therapy for AS and briefly summarize the relevant factors that induce the formation of AS. We mainly discuss the efficacy and application prospects of mesenchymal stem cells (MSCs) for the treatment of AS, in addition to the partial role and potential of exosomes in the treatment of AS. Further, provide new ideas for the clinical application of stem cells.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Exossomos , Transplante de Células-Tronco Mesenquimais , Humanos , Doenças Cardiovasculares/metabolismo , Transplante de Células-Tronco , Aterosclerose/terapia , Aterosclerose/metabolismo , Exossomos/metabolismo , Terapia Baseada em Transplante de Células e Tecidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...