RESUMEN
Inflammation assumes a pivotal role in the aortic remodeling of aortic dissection (AD). Asiatic acid (AA), a triterpene compound, is recognized for its strong anti-inflammatory properties. Yet, its effects on ß-aminopropionitrile (BAPN)-triggered AD have not been clearly established. The objective is to determine whether AA attenuates adverse aortic remodeling in BAPN-induced AD and clarify potential molecular mechanisms. In vitro studies, RAW264.7 cells pretreated with AA were challenged with lipopolysaccharide (LPS), and then the vascular smooth muscle cells (VSMCs)-macrophage coculture system was established to explore intercellular interactions. To induce AD, male C57BL/6J mice at three weeks of age were administered BAPN at a dosage of 1 g/kg/d for four weeks. To decipher the mechanism underlying the effects of AA, RNA sequencing analysis was conducted, with subsequent validation of these pathways through cellular experiments. AA exhibited significant suppression of M1 macrophage polarization. In the cell coculture system, AA facilitated the transformation of VSMCs into a contractile phenotype. In the mouse model of AD, AA strikingly prevented the BAPN-induced increases in inflammation cell infiltration and extracellular matrix degradation. Mechanistically, RNA sequencing analysis revealed a substantial upregulation of CX3CL1 expression in BAPN group but downregulation in AA-treated group. Additionally, it was observed that the upregulation of CX3CL1 negated the beneficial impact of AA on the polarization of macrophages and the phenotypic transformation of VSMCs. Crucially, our findings revealed that AA is capable of downregulating CX3CL1 expression, accomplishing this by obstructing the nuclear translocation of NF-κB p65. The findings indicate that AA holds promise as a prospective treatment for adverse aortic remodeling by suppressing the activity of NF-κB p65/CX3CL1 signaling pathway.
Asunto(s)
Disección Aórtica , Quimiocina CX3CL1 , Ratones Endogámicos C57BL , Triterpenos Pentacíclicos , Transducción de Señal , Factor de Transcripción ReIA , Remodelación Vascular , Animales , Ratones , Masculino , Disección Aórtica/metabolismo , Disección Aórtica/patología , Disección Aórtica/tratamiento farmacológico , Triterpenos Pentacíclicos/farmacología , Remodelación Vascular/efectos de los fármacos , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Factor de Transcripción ReIA/metabolismo , Quimiocina CX3CL1/metabolismo , Quimiocina CX3CL1/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Aminopropionitrilo/farmacología , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/efectos de los fármacosRESUMEN
Abdominal aortic aneurysm (AAA) represents the serious vascular degenerative disorder, which causes high incidence and mortality. Alpha-ketoglutarate (AKG), a crucial metabolite in the tricarboxylic acid (TCA) cycle, has been reported to exert significant actions on the oxidative stress and inflammation. However, its role in AAA still remains elusive. Herein, we examined the effects of AKG on the formation of AAA. The study established an elastase-induced mouse abdominal aortic aneurysms model as well as a TNF-α-mediated vascular smooth muscle cells (VSMCs) model, respectively. We displayed that AKG pre-treatment remarkably prevented aneurysmal dilation assessed by diameter and volume and reduced aortic rupture. In addition, it was also observed that AKG treatment suppressed the development of AAA by attenuating the macrophage infiltration, elastin degradation and collagen fibers remodeling. In vitro, AKG potently decreased TNF-α-induced inflammatory cytokines overproduction, more apoptotic cells and excessive superoxide. Mechanistically, we discovered that upregulation of vpo1 in AAA was significantly suppressed by AKG treatment. By exploring the RNA-seq data, we found that AKG ameliorates AAA mostly though inhibiting oxidative stress and the inflammatory response. PXDN overexpression neutralized the inhibitory effects of AKG on ROS generation and inflammatory reaction in MOVAS. Furthermore, AKG treatment suppressed the expression of p-ERK1/2, 3-Cl Tyr in vivo and in vitro. ERK activator disrupted the protective of AKG on TNF-α-induced VSMCs phenotypic switch. Conclusively, AKG can serve as a beneficial therapy for AAA through regulating PXDN/HOCL/ERK signaling pathways.
Asunto(s)
Aneurisma de la Aorta Abdominal , Animales , Aneurisma de la Aorta Abdominal/inducido químicamente , Aneurisma de la Aorta Abdominal/tratamiento farmacológico , Aneurisma de la Aorta Abdominal/metabolismo , Colágeno/metabolismo , Citocinas/metabolismo , Desoxirribonucleósidos , Modelos Animales de Enfermedad , Elastina/metabolismo , Inflamación/metabolismo , Ácidos Cetoglutáricos , Sistema de Señalización de MAP Quinasas , Ratones , Ratones Endogámicos C57BL , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Elastasa Pancreática/metabolismo , Nucleósidos de Purina , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Superóxidos/metabolismo , Ácidos Tricarboxílicos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Purpose: To evaluate the safety and efficacy of total endovascular repair with parallel stent-grafts for postoperative residual dissection thoracoabdominal aortic aneurysm (TAAA). Materials and Methods: A retrospective study was undertaken of 21 patients (mean age 64.0±12.5 years; 17 men) undergoing total endovascular therapy with parallel stent-grafts for postdissection TAAA after prior proximal repair between 2014 and 2016. The preoperative minimum true lumen diameter was 12.3±4.8 mm and the mean extent of dissection was 248.1±48.2 mm. Pre-, intra-, and postoperative medical records were reviewed to assess technical success, spinal cord ischemia, patency of target branch arteries, endoleak, and short-term outcomes of this approach. Results: Technical success was achieved in 17 of 21 patients owing to 4 type I endoleaks at the end of the procedures. A total of 70 branch arteries were revascularized and 14 celiac trunks were covered intentionally without reconstruction. Of 7 intraoperative endoleaks, 2 were managed intraoperatively and 5 (4 type I and 1 type II) disappeared spontaneously within 1 month. No spinal cord or abdominal organ or limb ischemia was observed. Mean follow-up was 16.2±6.1 months. No death or type I or III endoleak occurred during the follow-up; 2 type II endoleaks were observed. Nineteen of the 21 false lumens thrombosed, and the total aortic diameter decreased (57.3±8.4 to 55.3±7.4 mm, p<0.01). Three (4.3%) of 70 target branch arteries occluded during follow-up. The cumulative patency of retrogradely and antegradely revascularized branch arteries was 97.3% vs 100% at 12 months and 91.2% vs 100% at 18 months. Conclusion: Total endovascular therapy with parallel stent-grafts could be an effective alternative in treating postdissection TAAA. Further studies with long-term follow-up and larger sample size are recommended to evaluate the technique.
Asunto(s)
Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular/instrumentación , Prótesis Vascular , Procedimientos Endovasculares/instrumentación , Stents , Adulto , Anciano , Anciano de 80 o más Años , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/fisiopatología , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/fisiopatología , Implantación de Prótesis Vascular/efectos adversos , Endofuga/etiología , Endofuga/fisiopatología , Endofuga/cirugía , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
Deep vein thrombosis (DVT) is a venous return disorder caused by abnormal clotting of blood in deep veins. After thrombosis, most of the thrombus will spread to the deep vein trunk throughout the limb. If DVT is not treated in time, most of them will develop into thrombosis sequelae and even threaten life. Intravenous thrombolytic drugs are the most promising strategy for treating DVT, but current drugs used for thrombolysis suffer from short half-lives and narrow therapeutic indexes. To effectively manage DVT, it is necessary to develop a novel multifunctional drug-loading system to effectively prolong the treatment time and improve the therapeutic efficacy. In this study, a urokinase-loaded protocatechuic aldehyde-modified chitosan microsphere drug-loading platform was constructed for the treatment of DVT. This microsphere adsorbed urokinase well through electrostatic interaction, and the introduction of bovine serum albumin conferred stability to the microspheres. Therefore, the microsphere drug delivery system could achieve slow drug release to effectively dissolve blood fibrin. In addition, chitosan grafted with protocatechuic aldehyde imparted excellent antioxidant activity to the system to reduce free radicals in the blood vessels. Effective management of oxidative stress could avoid abnormal platelet activation and new thrombus formation. The experimental results showed that this microsphere had good biocompatibility, anti-inflammatory properties, and considerable thrombolytic activity. In conclusion, this study provided a new direction and developed a novel multi-functional nano microsphere drug delivery platform for the treatment of DVT.
RESUMEN
OBJECTIVE: Research suggests that fine particulate matter (PM2.5) contributes to the expansion and development of atherosclerosis. Infiltration and proliferation of vascular smooth muscle cells (VSMCs) from the blood vessel media into the intima, is an important step in the atherosclerosis pathophysiology. Afrocyclamin A, is an oleanane-type triterpene saponin, isolated from Androsace umbellate, which is commonly used in Chinese herbal medicine. In the study, we examined the effect of Afrocyclamin A on PM2.5-induced VSMCs proliferation and scrutinized possible mechanisms of action. MATERIALS AND METHODS: In the experimental study, counting Kit-8 (CCK-8) assay was used for estimation of VSMCs viability. BrdU immunofluorescence was used for estimation of VSMCs proliferation. The levels of antioxidant parameters such as malonaldehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH); proinflammatory cytokines such as interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), nitric oxide (NO), endothelin-1 (ET-1), and vascular cell adhesion molecule-1 (VCAM-1), were estimated. The expression of proliferating cell nuclear antigen (PCNA) and phospho-p38 MAPK (p-p38 MAPK) was assessed. RESULTS: Compared to PM2.5-treated cells, in addition to reducing PM2.5-induced VSMCs proliferation, Afrocyclamin A reduced the expression of PCNA and p-p38 MAPK, down-regulated the level of TNF-α, IL-1ß, IL-6, VCAM-1, MDA and ET-1, and up-regulated SOD, GSH and NO level. Furthermore, the anti-proliferative effect of Afrocyclamin A was considerably increased following co-incubation of Afrocyclamin A with SB203580 (p38 MAPK inhibitor) in comparison with Afrocyclamin A-treated cells. CONCLUSION: Based on the results, we can conclude that Afrocyclamin A might reduce PM2.5-induced VSMCs proliferation via reduction of p38 MAPK signaling pathway.
RESUMEN
This article published in Cell J (Yakhteh), Vol 23, No 2, 2021, on pages 191-198, corresponding author and corresponding address were changed based on authors' request. The authors would like to apologies for any inconvenience caused.
RESUMEN
This research is focussed to quantify IGF1 by electroanalytical analysis on InterDigitated electrode surface and characterized by the microscopic observations. For the detection, antibody and aptamer were used to analyze the level of IGF1. The sandwich pattern (aptamer-IGF1-antibody) was designed on the chemically modified IDE surface and reached the limit of detection to 10 fM with 100 folds enhancement in the sensitivity. Different control experiments (absence of IGF1, binding with IGF2 and with non-complementary aptamer) were failed to show the current changes, discriminated the specific detection. A good detection strategy is to complement the currently following imaging systems for AAA.