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In recent years, active substances have been extensively applied in the fields of food, cosmetics, and pharmaceuticals. However, their preservation and transportation have posed challenges due to issues such as oxidation and photodegradation. This study proposes a method for synthesizing Zein-Hyaluronic Acid (Zein-HA) conjugate particles via the Schiff base reaction, utilizing these conjugate particles to encapsulate and protect active substances within a stable emulsion system. Compared to zein, the modified conjugate particles exhibit significantly improved dispersibility, amphiphilicity, interfacial affinity, and emulsifying properties. Consequently, these particles are capable of stabilizing high internal phase Pickering emulsions with an oil phase volume fraction of up to 80 (v/v)%, thereby enabling the carriage of a higher load of active components. Furthermore, the prepared emulsions demonstrate excellent storage stability, resistance to ionic strength (250-2000 mM NaCl), and outstanding antioxidative characteristics. Moreover, after 8 h of UV light exposure, the retention rates of the active substances (curcumin, astaxanthin, and resveratrol) exceed 60 %. Therefore, these emulsions hold substantial potential to be applied as a carrier system in the food, cosmetics, and pharmaceutical industries.
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BACKGROUND: Myocardial hypertrophy is a chronic cardiac condition that often occurs from long-term pressure or volumetric load on the heart. Propranolol hydrochloride has been employed in research on hypertension, pheochromocytoma, myocardial infarction, arrhythmias, angina pectoris, and hypertrophic cardiomyopathy. Current treatments for this condition have side effects, such as arrhythmias and myocardial cell death, thus necessitating safer and more effective alternatives. Recently, natural products have gained attention in drug development because of their low toxicity and high efficacy. Cardamonin, a compound derived from Chinese herbal materials, has shown potential in inhibiting oxidative stress and inflammation, which is beneficial for cardiovascular health. Nevertheless, the impact on myocardial hypertrophy and cardiac remodeling is still uncertain METHODS: Approach We employed a transverse aortic constriction (TAC)model to simulate the pathological conditions of myocardial hypertrophy. Mice were administered varying doses of CAR (10 and 40 mg kg-1/d), and cardiac function was assessed using techniques such as echocardiography, qPCR, Masson staining, DHE staining, immunofluorescence, and immunohistochemistry. Propranolol hydrochloride was the positive control for observing the anti-myocardial hypertrophic effects of CAR. RESULTS: Cardamonin significantly reduced TAC-induced myocardial hypertrophy, fibrosis, inflammation, and oxidative stress. High CAR concentrations showed better anti-myocardial remodeling effects. The anti-hypertrophic effect of cardamonin was similar to that of propranolol hydrochloride. Further investigating the mechanism of action revealed that ubiquitin-specific peptidase (USP)18, a deubiquitnating enzyme that regulates various cellular signaling pathways, was a key downstream regulator affected by cardamonin. To confirm this, AAV9-cTNT-Usp18 and Usp18 myocardial-specific knockout mice were generated and treated with TAC. Usp18 downregulation was found to interfere with the protective effects of CAR against myocardial remodeling, whereas its overexpression enhanced these effects. CONCLUSION: This study used propranolol as a positive control and provided the first in-depth exploration of the concentration-dependent effects of cardamonin on myocardial hypertrophy and cardiac remodeling. CAR is a new candidate drug for cardiovascular disease treatment. This comparative study provides evidence for assessing the clinical application potential of new drugs and delves into its mechanisms of action, particularly the interaction with Usp18. Comprehending these mechanisms is beneficial for formulating more targeted future treatment approaches.
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Surface ligands play crucial roles in modifying the properties of metal nanoclusters and stabilizing atomically precise structures, and also serve as vital linkers for constructing cluster-based coordination polymers. In this study, we present the results of the solvothermal synthesis of eight novel copper alkynyl clusters incorporating pyridine ligands using a one-pot method. The resulting compounds underwent characterization through elemental analysis, Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), and single-crystal X-ray diffraction (SCXRD). Our observations revealed that distinct pyridine ligands with varying lengths and coordination sites exert significant influence on the structure and dimensionality of the clusters. The structural diversity of these clusters led to the formation of one-dimensional (1D), two-dimensional (2D), or dimer arrangements linked by seven pyridine bridging ligands. Remarkably, these complexes exhibited unique UV-vis absorption and photoluminescence properties, which were influenced by the specific bridging ligand and structural framework. Furthermore, density functional theory (DFT) calculations demonstrated the capability of the conjugated system in the pyridine ligand to impact the band gap of clusters. This study not only unveils the inherent structural diversity in coordination polymers based on copper alkynyl clusters but also offers valuable insights into harnessing ligand engineering for structural and property modulation.
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Among various biopolymers, protein particles are widely used for stabilizing Pickering emulsions, yet their emulsifying ability are easily influenced by the ion concentration, pH, and high temperatures. To address these challenges, this study utilized chemical modification to prepare pea protein isolate-polyglycerol (PPI-PG) conjugates by Schiff-base reaction. Compared with other chemical modifications, this method produces conjugate particles with excellent biocompatibility, capable of promoting cell proliferation by up to 177 %. These conjugates showed improved dispersibility, with diffusion coefficients 3.5 times greater than pure PPI, and the isoelectric points shift from pH 4.6 to pH 1.5, which contribute to the pH stability of emulsions (pH 3-9). Additionally, the anisotropic nature of the conjugate particles, with a three-phase contact angle close to 90°, make particles need more energy for detachment from the oil-water interface, leading to good thermal stability of emulsion (80 °C, 48 h). Notably, after conjugation, these particles rely more on PG chains for dispersibility, which are less affected by ions, resulting in emulsions with high ionic strength resistance (3000 mM). Furthermore, the prepared Pickering emulsion demonstrates remarkable antioxidative properties (only a 10 % decrease), indicating widely potential applications in food, cosmetics, and pharmaceutical sectors.
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Materiales Biocompatibles , Emulsiones , Glicerol , Proteínas de Guisantes , Polímeros , Emulsiones/química , Concentración Osmolar , Glicerol/química , Polímeros/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Proteínas de Guisantes/química , Antioxidantes/química , Antioxidantes/farmacología , Concentración de Iones de Hidrógeno , Animales , Tamaño de la PartículaRESUMEN
The southwest region of China has abundant groundwater and high-temperature geothermal energy. Carbonaceous shale, as one of the typical surrounding rocks in this region, often suffers from deterioration effects due to the coupled action of groundwater chemical erosion and high temperature, which affects the long-term stability of tunnel engineering. In order to investigate the deterioration effects of carbonaceous shale under the coupled action of chemical erosion and high temperature, carbonaceous shale from a tunnel of Lixiang Railway in Yunnan Province was taken as the research object. The microstructure and mineral composition of the samples before and after chemical erosion were obtained with a scanning electron microscope-energy dispersive spectrometer and an X-ray diffraction test. Then, triaxial compression tests were conducted on the samples under different time points and different temperature effects of chemical erosion, and the stress-strain curves and the deterioration laws under a single factor were obtained. An improved numerical simulation method based on the parallel bond model was developed, which can account for the coupled effects of chemical erosion and high temperature on the rock. By simulating the triaxial compression test of carbonaceous shale, the deterioration law of carbonaceous shale under the coupled action was discussed. The results show that chemical erosion has a significant deterioration effect on the triaxial compressive strength of carbonaceous shale, and the degree of deterioration is related to the erosion time. In the first 30 days of erosion, the triaxial compressive strength of carbonaceous shale decreased by 11.38%, which was the largest deterioration range. With the increase in erosion time, the deterioration rate gradually decreased; temperature had a significant threshold effect on the strength of carbonaceous shale, and a clear turning point appeared at about 200 °C. By simulating the deterioration effects of carbonaceous shale under the coupled action of chemical erosion and high temperature, it was found that the longer the duration of chemical erosion, the stronger the temperature sensitivity of carbonaceous shale, and the more serious the loss of compressive strength during the heating process. When the temperature was low, the strength of carbonaceous shale changed little, and some samples even showed an increase in strength; when the temperature was high, the strength of carbonaceous shale decreased significantly, showing deterioration characteristics. The numerical simulation method was compared and verified with the indoor test results, and it was found that the numerical calculation had a good agreement with the test results.
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Alloying nanoclusters (NCs) has emerged as a widely explored and versatile strategy for tailoring tunable properties, facilitating in-depth atomic-level investigations of structure-property correlations. In this study, we have successfully synthesized six atomically precise copper NCs alloyed with Group 10 metals (Pd or Pt). Notably, the Pd0 or Pt0 atom situated at the center of the distorted hexagonal antiprism Pd0/Pt0@Cu12 cage, coordinated with twelve Cu+ and two tBuC≡C- ligands. Moreover, ligand exchange strategies demonstrated the potential for Cl- and Br- to replace one or two alkynyl ligands positioned at the top or side of the NCs. The chirality exhibited by these racemic NCs is primarily attributed to the involvement of halogens and a chiral (Pd/Pt)@Cu18 skeleton. Furthermore, all the NCs exhibit near-infrared (NIR) luminescence, characterized by emission peaks at 705-755â nm, lifetimes ranging from 6.630 to 9.662â µs, and absolute photoluminescence quantum yields (PLQYs) of 1.75 %-2.52 % in their crystalline state. The experimental optical properties of these NCs are found to be in excellent agreement with the results of theoretical calculations. These alloy NCs not only offer valuable insights into the synthesis of Pd0/Pt0-Cu alloy NCs, but also bridge the gap in understanding the structure-luminescence relationships of Pd0/Pt0-Cu molecules.
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Bio-based emulsifiers hold significant importance in various industries, particularly in food, cosmetics, pharmaceuticals and other related fields. In this study, pea protein isolate (PPI) and fucoidan (FUD) were conjugated via the Maillard reaction, which is considered safe and widely used in the preparation of food particle. The PPI-FUD conjugated particles exhibit an anisotropic non-spherical structure, thereby possessing a high detachment energy capable of preventing emulsion coalescence and Ostwald ripening. Compared to emulsions previously prepared in other studies (< 500 mM), the Pickering emulsion stabilized by PPI-FUD conjugate particles demonstrates outstanding ionic strength resistance (up to 5000 mM). Furthermore, when encapsulating curcumin, the Pickering emulsion protects the curcumin from oxidation. Additionally, the formulated emulsions demonstrated the capability to incorporate up to 60 % (v/v) oil phase, revealing remarkable performance in terms of storage stability, pH stability, and thermal stability.
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Curcumina , Proteínas de Guisantes , Polisacáridos , Emulsiones/química , Curcumina/química , Reacción de Maillard , Tamaño de la PartículaRESUMEN
BACKGROUND: We assessed the impact of pre- and postprocedural plasma corin levels on the recurrence of atrial fibrillation (AF) after catheter ablation (CA). METHODS AND RESULTS: This prospective, single-center, observational study included patients undergoing their first CA of AF. Corin was measured before and 1 day after CA. The primary end point was recurrent AF between 3 and 12 months after ablation. From April 2019 through May 2021, we analyzed 616 patients with AF (59.09% men) with a mean age of 62.86±9.42 years. Overall, 153 patients (24.84%) experienced recurrent AF. In the recurrence group, the pre- and postprocedure corin concentrations were 539.14 (329.24-702.08) and 607.37 (364.50-753.80) pg/mL, respectively, which were significantly higher than the nonrecurrence group's respective concentrations of 369.05 (186.36-489.28) and 489.12 (315.66-629.05) pg/mL (both P<0.0001). A multivariate Cox regression analysis with confounders found that elevated preablation corin levels were significantly associated with an increased risk of AF recurrence after CA. Receiver operating characteristic curve analysis identified that a preablation corin threshold of >494.85 pg/mL predicted AF recurrence at 1 year. An increase of 1 SD in corin concentrations before CA (264.94 pg/mL) increased the risk of recurrent AF by 54.3% after adjusting for confounding variables (hazard ratio, 1.465 [95% CI, 1.282-1.655]; P<0.0001). CONCLUSIONS: Plasma corin levels at baseline is a valuable predictor of AF recurrence after CA, independent of established conventional risk factors. Risk stratification before ablation for AF may be useful in selecting treatment regimens for patients.
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Fibrilación Atrial , Ablación por Catéter , Masculino , Humanos , Persona de Mediana Edad , Anciano , Femenino , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Resultado del Tratamiento , Estudios Prospectivos , Curva ROC , Factores de Riesgo , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , RecurrenciaRESUMEN
The heart undergoes pathological cardiac hypertrophy as an adaptive response to prolonged pathological stimulation, leading to cardiomyocyte hypertrophy, fibroblast proliferation, and an increase in extracellular matrix. Chinese medicine monomers are now receiving much attention for the treatment of cardiac hypertrophy and myocardial remodeling. Biochanin A (BCA) is a kind of flavonoid structural monomer, which has a certain therapeutic effect on bone thinning disease, aging syndrome, lung cancer, etc. Moreover, it exhibits hypoglycemic, anti-inflammatory, anti-oxidation, anti-bacteria and other pharmacological properties. It is still unknown whether BCA has an impact on the mechanism of TAC-induced cardiac hypertrophy. Here, cardiac remodeling was induced by TAC. BCA was injected intraperitoneally at 25 and 50 mg/kg/day one week in advance. Masson, WGA, DHE and other pathological staining and serum were used to detect the inhibitory effect of BCA on cardiac hypertrophy in mice. The anti-hypertrophic effect of BCA was demonstrated by studying the pathological manifestations of Neonatal rat cardiomyocytes (NRCMs) and cardiac fibroblasts (CFs) in vitro. The results showed that BCA significantly reduced TAC-induced fibrosis, inflammation, oxidative stress, and myocardial hypertrophy. BCA inhibited Ang II-induced cell hypertrophy and oxidative stress in NRCMs in vitro and Ang II-induced CF migration, proliferation, and collagen secretion. This suggests that BCA plays a key role in inhibiting the progression of myocardial remodeling, suggesting that BCA may be a promising agent for the treatment of myocardial hypertrophy and fibrosis.
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Cardiomegalia , Miocardio , Ratas , Ratones , Animales , Cardiomegalia/patología , Miocardio/patología , Miocitos Cardíacos , Fibrosis , Ratones Endogámicos C57BL , Angiotensina II/farmacología , Remodelación VentricularRESUMEN
A comparative study of structure-property relationships in isomeric and isostructural atomically precise clusters is an ideal approach to unravel their fundamental properties. Herein, seven high-nuclearity copper(i) alkynyl clusters utilizing template-assisted strategies were synthesized. Spherical Cu36 and Cu56 clusters are formed with a [M@(V/PO4)6] (M: Cu2+, Na+, K+) skeleton motif, while peanut-shaped Cu56 clusters feature four separate PO4 templates. Experiments and theoretical calculations suggested that the photophysical properties of these clusters are dependent on both the inner templates and outer phosphonate ligands. Phenyl and 1-naphthyl phosphate-protected clusters exhibited enhanced emission features attributed to numerous well-arranged intermolecular C-Hâ¯π interactions between the ligands. Moreover, the electrocatalytic CO2 reduction properties suggested that internal PO4 templates and external naphthyl groups could promote an increase in C2 products (C2H4 and C2H5OH). Our research provides new insight into the design and synthesis of multifunctional copper(i) clusters, and highlights the significance of atomic-level comparative studies of structure-property relationships.
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Gliomas are the most common primary brain tumors in adults. Although they exist in different malignant stages, most gliomas are clinically challenging because of their infiltrative growth patterns and inherent relapse tendency with increased malignancy. Epigenetic alterations have been suggested to be an important factor for glioma genesis. Using mRNA probe hybridization, we identified SUMO-specific protease 1 (SENP1) as the most significantly upregulated SUMOylation regulator in glioma. Moreover, SENP1 was overexpressed in gliomas and predicted poor prognoses. Depletion of SENP1 reduced glioma cell activity, cycle arrest, and increased apoptotic activity. Mechanistically, SENP1 inhibited the protein expression of sirtuin 1 (SIRT1) through de-SUMOylation, and SIRT1 inhibited the activity of nuclear factor kappaB (NF-κB) by deacetylation. Rescue experiments revealed that downregulation of SIRT1 reversed the inhibitory effect of sh-SENP1 on glioma cell malignant phenotype, while downregulation of NF-κB reversed the activating effect of sh-SIRT1 on glioma cell malignant phenotype. Thus, SENP1-mediated de-SUMOylation of SIRT1 might be therapeutically important in gliomas.
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A difference in encaged non-metallic element (i.e., C2versus O) leads to a clear change of intramolecular interactions and shifts in redox potentials of Lu2C2@C2(13333)-C74 and Lu2O@C2(13333)-C74, as a result of their distinct molecular orbital energy levels. Different from these two endoherals whose HOMOs are located on the cage, experimentally absent Lu2@C2(13333)-C74 possesses a HOMO predominantly delocalized on the internal Lu-Lu bond, accompanied by a much smaller HOMO-LUMO gap, suggesting that the presence of a non-metallic unit broadens the electrochemical gaps and consequently improves the kinetic stability. These findings shed light on the role of non-metallic moieties in clusterfullerenes, providing valuable insights into the stability and properties of metallofullerenes.
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Doxorubicin, a widely used chemotherapeutic drug in clinical oncology, causes a series of cardiac side effects referred to as doxorubicin-induced cardiotoxicity. Hyperhomocysteinaemia is an independent risk factor for multiple cardiovascular diseases. However, whether hyperhomocysteinaemia contributes to doxorubicin-induced cardiotoxicity is currently unknown. In this study, we explored the pathogenic effects of hyperhomocysteinaemia induced by dietary methionine supplementation (2% wt/wt in rodent chow) in a mouse model of doxorubicin-induced cardiotoxicity. Our data showed that methionine supplementation doubled serum homocysteine levels, inducing mild hyperhomocysteinaemia. Doxorubicin at a cumulative dosage of 25 mg/kg body weight led to significant weight loss and severe cardiac dysfunction, which were further exacerbated by methionine-induced mild hyperhomocysteinaemia. Doxorubicin-induced cardiac atrophy, cytoplasmic vacuolisation, myofibrillar disarray and loss, as well as cardiac fibrosis, were also exacerbated by methionine-induced mild hyperhomocysteinaemia. Additional folic acid supplementation (0.006% wt/wt) prevented methionine-induced hyperhomocysteinaemia and inhibited hyperhomocysteinaemia-aggravated cardiac dysfunction and cardiomyopathy. In particular, hyperhomocysteinaemia increased both serum and cardiac oxidative stress, which could all be inhibited by folic acid supplementation. Therefore, we demonstrated for the first time that hyperhomocysteinaemia could exacerbate doxorubicin-induced cardiotoxicity in mice, and the pathogenic effects of hyperhomocysteinaemia might at least partially correlate with increased oxidative stress and could be prevented by folic acid supplementation. Our study provides preliminary experimental evidence for the assessment of hyperhomocysteinaemia as a potential risk factor for chemotherapy-induced cardiotoxicity in cancer patients.
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Metal clusters have become increasingly important in various applications, with ligands playing a crucial role in their construction. In this study, we synthesized a bimetallic cluster, Ag6 Cu8 (C=CAr)14 (DPPB)2 (Ag6 Cu8 ), using a rigid acetylene ligand, 3,5-bis(trifluoromethyl)phenylacetylide. Through single-crystal structure characterization, we discovered that the butterfly-shaped Ag2 Cu2 motifs were subject to distortion due to steric hindrance imposed by the rigid ligand. These motifs assembled together through shared vertices and edges. Mass spectrometry analysis revealed that the primary fragments detected during electrospray ionization (ESI) testing corresponded to the Ag2 Cu2 motifs. Furthermore, we conducted a comprehensive investigation of the cluster's solution properties employing 31 P NMR, UV-vis absorption, and photoluminescent measurements. In contrast to previously reported Ag/Cu bimetallic clusters protected by flexible ligands, Ag6 Cu8 protected by rigid ligands exhibited intriguing room temperature fluorescence properties alongside excellent thermal stability. DFT calculations on Ag6 Cu8 and Ag6 Cu8 with the rigid aromatic ring removed revealed that the presence of the rigid aromatic ring can lower the electronic energy levels of the cluster, and reduce the energy gap from 4.05â eV to 3.45â eV. Moreover, the rigid ligand further suppressed the non-radiative transition process, leading to room temperature fluorescence emission.
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This paper presents a novel routing planning method based on multi-objective optimization to tackle the routing problem in computing power networks. The proposed method aims to improve the performance and efficiency of routing by considering multiple objectives. In this study, we first model the computing power network and formulate the routing problem as a multi-objective optimization problem. To address this problem, we introduce a non-dominated sorting genetic algorithm incorporating a ratio parameter adjustment strategy based on reinforcement learning. Extensive simulations are conducted to evaluate the performance of the proposed routing algorithm. The results demonstrate significant client latency and cost reductions, highlighting the algorithm's effectiveness. By providing a comprehensive solution to the routing problem in computing power networks, this work contributes to the field by offering improved performance and efficiency. The proposed method's ability to optimize multiple objectives sets it apart from existing approaches, making it a valuable contribution to the research community.
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Tunnel projects in the southwestern mountainous area of China are in full swing. According to the tunnel burial depth, structural characteristics, and chemical erosion environments of the Lixiang railway tunnel, carbonaceous slate specimens obtained in the field were taken to experimentally investigate the physical, mechanical, and creep characteristics of the bedding's slate specimens after chemical erosion. The results of scanning electron microscopy (SEM) indicate that chemical erosion leads to internal damage in the carbonaceous slate specimens, and the internal damages are increasing with the increase of erosion days. Moreover, the specimens' ultrasonic test (UT) results prove that specimens with smaller bedding angles suffer a more serious erosion and induce more internal cracks. Under conventional triaxial compression conditions with 40 MPa of confining pressures, the conventional triaxial compressive strength (σs) decreases with the decrease of the bedding angle and the increase of erosion days, and the failure modes of the specimens are mainly controlled by oblique shear fractures and accompanied by the occurrence of slip dislocation fractures between the bedding inclination. Under creep conditions with 40 MPa of confining pressures, the final deformations of specimens are increasing with the increase of erosion days, which means the longer the erosion days, the greater the deformations. The failure modes of the specimens under creep conditions are controlled by shear fractures, and for the specimen with a 60° bedding angle and long-term erosion, there are block separations and many cavities along the shear planes. Therefore, more attention should be paid to prevent serious failure of the surrounding rock if the surrounding rock has a bedding angle of 60° or suffers long-term erosion.
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Hypertriglyceridemia (HTG) is an independent risk factor for atherosclerosis. However, its impact on non-atherosclerotic cardiovascular diseases remains largely unknown. Glycosylphosphatidylinositol anchored high-density lipoprotein binding protein 1 (GPIHBP1) is essential for the hydrolysis of circulating triglycerides and loss of functional GPIHBP1 causes severe HTG. In this study, we used Gpihbp1 knockout (GKO) mice to investigate the potential effects of HTG on non-atherosclerotic vascular remodeling. We compared the aortic morphology and gene expressions between three-month-old and ten-month-old GKO mice and their age-matched wild-type controls. We also conducted similar comparisons between GKO mice and wild-type controls in an angiotensin II (AngII)-induced vascular remodeling model. Our data showed that the intima-media wall of ten-month-old GKO mice but not three-month-olds was significantly thickened compared to wild-type controls. Moreover, ten-month-old GKO mice but not three-month-olds had increased aortic macrophage infiltration and perivascular fibrosis, along with increased endothelial activation and oxidative stress. Similarly, the AngII-induced vascular remodeling, as well as endothelial activation and oxidative stress, were also exacerbated in the GKO mice compared to wild-type controls. In conclusion, we demonstrated that severe HTG caused by Gpihbp1 deficiency could facilitate the onset and progression of non-atherosclerotic vascular remodeling through endothelial activation and oxidative stress in mice.