Atherosclerosis In Rats Research Articles

Immunoexpression of aortic endothelial P-selectin and serum apolipoprotein A-1 levels after administration of arabica (Coffea arabica) and robusta (Coffea canephora) coffee bean extracts: In vivo study in atherosclerosis rat model.

Atherosclerosis is a leading cause of cardiovascular disease-related death worldwide. Some studies suggested that the natural ingredients in coffee may negatively affect cardiovascular diseases, while other studies indicated that coffee contains anti-inflammatory compounds that are beneficial for cardiovascular diseases. The aim of this study was to measure the expression of P-selectin in aortic endothelial cells and the level of serum apolipoprotein A-1 (ApoA-1) in an atherosclerosis rat model after the administration of arabica and robusta coffee bean extracts at mild-moderate and high doses. An experimental study was conducted with a complete randomized design using 36 adult male white rats (Rattus norvegicus) divided into six groups: negative control (NC), positive control (PC), arabica mild-moderate dose (A1), arabica high dose (A2), robusta mild-moderate dose (R1), and robusta high dose (R2). Animals were induced atherosclerosis with atherogenic feed and then were treated with arabica and robusta coffee bean extracts at two different doses for four weeks. The results showed that the expression of P-selectin in the group of rats treated with robusta coffee bean extract was lower than arabica coffee bean extract group. Rats with robusta coffee bean extract mild-moderate dose had the highest ApoA-1 levels compared to other groups significantly (p<0.05). The level of ApoA-1 was higher in both mild-moderate and high dose of robusta coffee groups compared to the negative control group (both with p<0.001). In conclusion, mild-moderate intake of robusta coffee bean extract could reduce aortic P-selectin immunoexpression and increase serum ApoA-1 levels in an atherosclerosis rat model.

Ascorbic acid and calcitriol in improving endothelial dysfunction through inhibition of free radical in type 2 diabetes melitus: In vivo study in atherosclerosis rat model

Ascorbic acid and calcitriol in improving endothelial dysfunction through inhibition of free radical in type 2 diabetes melitus: In vivo study in atherosclerosis rat model

Improving the bioavailability and therapeutic efficacy of felodipine for the control of diabetes-associated atherosclerosis: In vitro and in vivo characterization

Felodipine has proven to be effective as an atherosclerosis therapy because it increases blood flow to the vessel wall. However, the poor solubility, low bioavailability, and hepatic first-pass metabolism of oral felodipine compromise its therapeutic effectiveness. The study’s goal is to create a nasal pH-sensitive hydrogel of felodipine-loaded invasomes (IPHFI) that will improve felodipine’s release, permeation, bioavailability, and efficacy as a potential diabetes-associated atherosclerosis therapy. According to the pre-formulation study, the felodipine-loaded invasomes formulation composed of phospholipid (3%w/v), cholesterol (0.16%w/v), ethanol (3%v/v) and cineole (1%v/v) was chosen as the optimum formulation. The optimum formulation was characterized in vitro and then mixed with a mixture of chitosan and glyceryl monooleate to make the IPHFI formulation. The IPHFI formulation enhanced the release and permeation of felodipine by 2.99 and 3-fold, respectively. To assess the efficacy and bioavailability of the IPHFI formulation, it was studied in vivo using an experimental atherosclerosis rat model. Compared to oral free felodipine, the nasal administration of the IPHFI formulation increased the bioavailability by 3.37-fold and decreased the serum cholesterol, triglycerides, LDL, and calcification score by 1.56, 1.53, 1.80, and 1.18 ratios, respectively. Thus, nasal IPHFI formulation may represent a promising diabetes-associated atherosclerosis therapy.

Sesame oil downregulates the expression of ADAMTS-4 in high-fat diet-induced atherosclerosis

Atherosclerosis is a chronic inflammatory disease forming plaques in medium and large-sized arteries. ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs-4) is an extracellular-matrix remodelling enzyme involved in the degradation of versican in the arterial wall. Recent reports indicated that increased expression of ADAMTS-4 is associated with plaque progression and vulnerability. Bioactive components of dietary oil, like sesame oil, are reported to have anti-inflammatory and antioxidant properties. Here, we studied the effect of sesame oil on regulating ADAMTS-4 in high-fat diet-induced atherosclerosis rat model. Our results indicated that sesame oil supplementation improved the anti-inflammatory and anti-oxidative status of the body. It also reduced atherosclerotic plaque formation in high-fat diet-fed rats. Our results showed that the sesame oil supplementation significantly down-regulated the expression of ADAMTS-4 in serum and aortic samples. The versican, the large proteoglycan substrate of ADAMTS-4 in the aorta, was downregulated to normal control level on sesame oil supplementation. This study, for the first time, reveals that sesame oil could down-regulate the expression of ADAMTS-4 in high-fat diet-induced atherosclerosis, imparting a new therapeutic potential for sesame oil in the management of atherosclerosis.

Citronellal improves endothelial dysfunction by affecting the stability of the GCH1 protein.

Endothelial dysfunction (ED) serves as the pathological basis for various cardiovascular diseases. Guanosine triphosphate cyclopyrrolone 1 (GCH1) emerges as a pivotal protein in sustaining nitric oxide (NO) production within endothelial cells, yet it undergoes degradation under oxidative stress, contributing to endothelial cell dysfunction. Citronellal (CT), a monoterpenoid, has been shown to ameliorate endothelial dysfunction induced by in atherosclerosis rats. However, whether CT can inhibit the degradation of GCH1 protein is not clear. It has been reported that ubiquitination may play a crucial role in regulating GCH1 protein levels and activities. However, the specific E3 ligase for GCH1 and the molecular mechanism of GCH1 ubiquitination remain unclear. Using data-base exploration analysis, we find that the levels of the E3 ligase Smad-ubiquitination regulatory factor 2 (Smurf2) negatively correlate with those of GCH1 in vascular tissues and HUVECs. We observe that Smurf2 interacts with GCH1 and promotes its degradation via the proteasome pathway. Interestingly, ectopic Smurf2 expression not only decreases GCH1 levels but also reduces cell proliferation and reactive oxygen species (ROS) levels, mostly because of increased GCH1 accumulation. Furthermore, we identify BH 4/eNOS as downstream of GCH1. Taken together, our results indicate that CT can obviously improve vascular endothelial injury in Type 1 diabetes mellitus (T1DM) rats and reverse the expressions of GCH1 and Smurf2 proteins in aorta of T1DM rats. Smurf2 promotes ubiquitination and degradation of GCH1 through proteasome pathway in HUVECs. We conclude that the Smurf2-GCH1 interaction might represent a potential target for improving endothelial injury.

C/EBPβ-Lin28a positive feedback loop triggered by C/EBPβ hypomethylation enhances the proliferation and migration of vascular smooth muscle cells in restenosis.

The main cause of restenosis after percutaneous transluminal angioplasty (PTA) is the excessive proliferation and migration of vascular smooth muscle cells (VSMCs). Lin28a has been reported to play critical regulatory roles in this process. However, whether CCAAT/enhancer-binding proteins β (C/EBPβ) binds to the Lin28a promoter and drives the progression of restenosis has not been clarified. Therefore, in the present study, we aim to clarify the role of C/EBPβ-Lin28a axis in restenosis. Restenosis and atherosclerosis rat models of type 2 diabetes (n = 20, for each group) were established by subjecting to PTA. Subsequently, the difference in DNA methylation status and expression of C/EBPβ between the two groups were assessed. EdU, Transwell, and rescue assays were performed to assess the effect of C/EBPβ on the proliferation and migration of VSMCs. DNA methylation status was further assessed using Methyltarget sequencing. The interaction between Lin28a and ten-eleven translocation 1 (TET1) was analysed using co-immunoprecipitation (Co-IP) assay. Student's t-test and one-way analysis of variance were used for statistical analysis. C/EBPβ expression was upregulated and accompanied by hypomethylation of its promoter in restenosis when compared with atherosclerosis. In vitroC/EBPβ overexpression facilitated the proliferation and migration of VSMCs and was associated with increased Lin28a expression. Conversely, C/EBPβ knockdown resulted in the opposite effects. Chromatin immunoprecipitation assays further demonstrated that C/EBPβ could directly bind to Lin28a promoter. Increased C/EBPβ expression and enhanced proliferation and migration of VSMCs were observed after decitabine treatment. Further, mechanical stretch promoted C/EBPβ and Lin28a expression accompanied by C/EBPβ hypomethylation. Additionally, Lin28a overexpression reduced C/EBPβ methylation via recruiting TET1 and enhanced C/EBPβ-mediated proliferation and migration of VSMCs. The opposite was noted in Lin28a knockdown cells. Our findings suggest that the C/EBPβ-Lin28a axis is a driver of restenosis progression, and presents a promising therapeutic target for restenosis.

Amstirdam coffee ameliorates Lp-PLA2 and the inflammatory response in an atherosclerosis mice

Coffee is a kind of daily beverage, and its correlation with cardiovascular disease and atherosclerosis is still debatable. The aim of this study is to investigate the effects of Amstirdam coffee extract (ACE) on lipoprotein-associated phospholipase A2 (Lp-PLA2) and the inflammatory response in atherosclerosis mouse models. The study used 25 Swiss male mice for five groups (n = 5): healthy mice fed a normal diet (N); mice fed a high-fat, high-fructose diet (HFFD); mice fed HFFD and treated with ACE at doses of 104 (D1), 520 (D2), and 5200 mg/kg BW (D3). The levels of Lp-PLA2, regulatory T cells (Tregs) (CD4+CD25+CD62L+, CD4+CD25+IL-10+, CD4+CD25+TGF-+), IL-10 (CD4+IL-10+), and TGF-B (CD4+TGF+) were analyzed using a flow cytometer. Histological analysis of the mouse aorta was done by hematoxylin and eosin (HE) staining. This study indicated a significant increase in total cholesterol (TC), triglyceride (TG), LDL, and Lp-PLA2 levels in the HFFD group. HFFD also reduced HDL, IL-10, and TGF produced by CD4 and Tregs compared with the normal group. ACE at all doses significantly reduced Lp-PLA2 levels compared with the HFFD group (p &amp;lt; 0.05). Interestingly, the administration of 520 mg/kg BW ACE (D2) increased the production of IL-10 significantly compared to other doses (p &amp;lt; 0.05). The D3 group possessed a high TGF- production and Treg expression level significantly different between groups (p &amp;lt; 0.05). Foam cells were mostly found in the aorta of the HFFD group compared to the normal and ACE treatment groups. This study suggested that ACE could reduce Lp-PLA2 enzyme activity and foam cell formation through the immunosuppressive activity of IL-10 and TGF cytokines.

Anti-Atherosclerosis and Anti-Hyperlipidemia Functions of Terminalia catappa Fruit.

Background: Atherosclerosis is a chronic pathological condition that has remained clinically silent for decades, and the epidemic has continued to be on the rise due to risk factors, including diet, lifestyle, hyperlipidemia, pathogenic microorganisms, and aging. Using various synthetic drugs in treating atherosclerosis is associated with a high risk of myositis, angioedema, myoglobinuria, and acute renal failure. Various side effects of the available drugs have been reported; attempts are underway to explore natural sources with antiatherosclerotic activity. Aim and objective: Using a diet-induced atherosclerosis rat model, the current study tested the hypothesis of antiatherosclerotic and antihyperlipidemic roles of Terminalia catappa fruit extracts. Materials and Methods: Atherosclerosis in Wistar rats was induced using an atherogenic diet. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), creatine kinase (CK), and lactate dehydrogenase (LDH) were determined using analytical kits. Results: Quantitative phytochemical analysis of the extracts demonstrated that the plant had flavonoids, saponins, tannins, terpenoids, alkaloids, cardiac glycosides, sterols, phenols, and anthraquinones. Diet-induced atherogenic Wistar rats showed a significant (p < 0.05) increase in total cholesterol, triglyceride, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol compared to the healthy control group; however, the atherogenic lipid profile was reversed by the treatment of T. catappa fruit extracts. The biochemical experiments demonstrate that T. catappa fruit extracts have an antihyperlipidaemic effect, shown by a decreased coronary risk index and the atherogenic index, and an increased cardioprotective index, compared to disease control. Conclusion: The current study indicates that T. catappa fruit extracts may contain bioactive molecules to treat atherosclerosis.

Ascorbic Acid vs Calcitriol in Influencing Monocyte Chemoattractant Protein-1, Nitric Oxide, Superoxide Dismutase, as Markers of Endothelial Dysfunction: In Vivo Study in Atherosclerosis Rat Model.

Ascorbic acid and calcitriol were frequently utilized in conjunction as therapy during the COVID-19 pandemic, and individuals with minor symptoms had notable improvements. There have been a few studies, often with conflicting findings, that examine the use of them for endothelium restoration and numerous clinical trial studies that failed to establish the efficacy. The aim of this study was to find the efficacy of ascorbic acid compared to calcitriol on the inflammatory markers monocyte chemoattractant protein-1 (MCP-1), nitric oxide (NO), and superoxide dismutase (SOD), as protective agents which play an important role in the early stages of atherosclerosis formation. This study was an experimental in vivo study. The total of 24 male Rattus norvegicus strain Wistar rats were divided into 4 groups, namely: control/normal group (N), atherosclerosis group (DL) given atherogenic diet, atherosclerosis group given atherogenic diet and ascorbic acid (DLC), and atherosclerosis group given atherogenic diet and calcitriol (DLD) treatment for 30 days. Ascorbic acid and calcitriol treatment was significantly effective (P<0.05) in lowering expression of MCP-1 and increasing NO and SOD level. Calcitriol was superior to ascorbic acid in increasing SOD (P<0.05). There was no significant difference between ascorbic acid and calcitriol in decreasing MCP-1 and increasing NO (P>0.05). Both treatments could reduce MCP-1, and increase NO and SOD by increasing antioxidants. In this study calcitriol was superior to ascorbic acid in increasing SOD, but not NO and decreasing MCP-1. According to the theory, it was found that calcitriol through nuclear factor erythroid 2-related factor 2 (Nrf2) causes a direct increase in the amount of SOD. Nrf2 is an emerging regulator of cellular resistance to oxidants. Ascorbic acid and calcitriol treatment was able to reduce MCP-1 and increase NO and SOD in atherosclerosis rat. Calcitriol was significantly superior in increasing SOD levels compared to ascorbic acid.

Quince extract resists atherosclerosis in rats by down-regulating the EGFR/PI3K/Akt/GSK-3β pathway

We identified the effective components and the underlying mechanisms of Quince (Cydonia oblonga Mill, COM) extract against atherosclerosis. The effective components of COM extract were identified with UHPLC-Q-TOF-MS/MS. Network pharmacology was performed. A rat model of atherosclerosis induced by high-fat emulsion combined with vitamin D3 was established. The anti-atherosclerosis effect of COM extract was evaluated from various aspects such as blood lipid regulation, anti-oxidative stress, anti-inflammatory response, and vascular protection function. We identified 14 serum components of COM extract using UHPLC-Q-TOF-MS/MS. Through prediction, 573 targets were obtained, among which 224 targets were atherosclerosis specific targets. The key targets included GSK3β, ESR1, EGFR, and HSP90AA1. The key signaling pathway was PI3K-Akt signaling pathway. Pharmacodynamics analysis showed that COM extract reduced the levels of TC, TG, and LDL-C as well as ALT and AST, while increased the level of HDL-C. Mechanistically, COM extract significantly increased serum SOD and GSH-Px activities, but decreased MDA content in atherosclerosis rats, showing antioxidant effects. Meanwhile, COM extract significantly down-regulated the levels of pro-inflammatory factors IL-1β, IL-6, TNF-α and CRP, but up-regulated anti-inflammatory factor IL-10. Additionally, COM extract increased the levels of NO, eNOS, and 6-keto-PGF1α; whereas, decreased the levels of ET-1 and TXB2. Furthermore, COM extract significantly inhibited the mRNA and protein levels of EGFR, p-PI3K, p-AKT, GSK-3β, Bax, and Caspase-3 as well as the Bax/Bcl-2 ratio. Conclusively, COM extract exerts hypolipidemic, anti-oxidative, anti-inflammatory, anti-thrombotic and vascular endothelium protective effects on atherosclerosis rat model, which may be related to the inhibition of EGFR/PI3K/AKT/GSK-3β signaling pathway.

Effect of Active Compounds for Quercus Fruit on Some Biochemical Parameters and Tissue Aorta in Induced Atherosclerosis Rats

This research included extractions of the active compounds from Quercus fruit, the identification of active compounds extract by using the capillary gas chromatography technique CGC and with high-performance liquid chromatography technology HPLC. The active dose of the aqueous extract (250 mg/kg) was studied in animals after induced arteriosclerosis with cholesterol (500mg/kg) dissolved in coconut oil for two weeks. The effect of the extracts oil, poly phenols, and at 7, 37.5, and 10 mg/kg respectively were studied also. The results showed a significant (P≤0.05) increase in catalase activity and the level of high density lipoprotein-cholesterol (HDL-C), However, there was a significant (P≤0.05) decrease in the high plasma kallikrein, caspase-3, cholesterol, triglycerides, and low-density lipoprotein cholesterol LDL-C in induced atherosclerosis rats treated with all extracts compared with affected control with the active extracts (oil, poly phenols) during the first and second week. The tissue aorta examination in the group of animals treated with the active extracts (aqueous, oily, flavonoid) after two weeks of the treatment showed that large parts of the tissues of the aorta were healed close to the normal state compared to the group of animals induced with atherosclerosis untreated whose tissues contained on thickenings and foam cells.

Opuntia ficus indica (L.) fruit extract alleviates oxidative stress through activation of dual oxidases and Keap1/Nrf2 signaling cascades in high-fat-diet associated atherosclerosis rats.

Atherosclerosis is a metabolic disorder characterized by chronic inflammation associated with progressive thickening and hardening of the large to medium-sized arteries due to plaque formation. The study aims to evaluate the antioxidative, anti-inflammatory, and hypolipidemic efficacy of Opuntia ficus-indica (OFI) fruit extract against the high-fat-diet associated atherosclerotic rat model. In-vitro qualitative and quantitative phytochemical screening of OFI fruit extract revealed the significant presence of total phenolic content and total flavonoid contents. In-vitro antioxidant activity of fruit extract was determined through 2,2-diphenyl-1-picrylhydrazyl and FRAP assays that have shown their protective efficacy against the overproduction of reactive oxygen species. Results revealed that the level of total oxidant stress was significantly (P<0.05) reduced and down expression levels of dual oxidases (Duox, Duoxa-1, and Duox-2) in all the treatment groups (I, II, III) as compared with positive control were observed. The total antioxidant capacity was significantly (P<0.05) increased in all treatment groups in comparison with the positive control group and higher expression level of the Nrf-2 signaling pathway (Nfe-212, NFR-1, and Keap-1) was observed in all the treatment groups compared with the positive control group. Histopathological examination of the aorta showed that high-fat diet markedly increased endothelial lining and thickness of tunica media and adventitia, with irregular media segments having wavy laminae, and a significant increase in entropy of fibers disposition was observed. Conclusively, OFI fruit extract has shown promising protective, anti-oxidative, and anti-inflammatory efficacy through the restoration of normal parenchyma in high-fat dieting-associated oxidative stress and endothelial inflammation.

VCAM-1-binding peptide targeted cationic liposomes containing NLRP3 siRNA to modulate LDL transcytosis as a novel therapy for experimental atherosclerosis

BackgroundActivation of NLRP3 inflammasome accelerates the formation of atherosclerotic plaques. Here, we evaluated the effects of inflammation on the expression of the NLRP3 inflammasome in endothelial cells (ECs). MethodsThe effect of TNF-α on transcytosis of LDL was measured. VCAM-1 binding peptide targeting cationic liposomes (PCLs) were prepared as siRNA vectors. Methylated NLRP3 siRNA was encapsulated into the PCLs to knock down NLRP3 in vitro and in vivo. In rats with partial carotid ligation, TNF-α-induced LDL retention in the carotid artery endothelium was observed. In ApoE−/− mice, NLRP3 siRNA-PCLs were injected intravenously to observe their effect on the formation of atherosclerosis. ResultsOur results showed that TNF-α upregulated NLRP3 in ECs, promoting the assembly of the NLRP3 inflammasome and processing of pro-IL-1β into IL-1β. Moreover, TNF-α accelerated LDL transcytosis in ECs. Knockdown of NLRP3 prevented TNF-α-induced NLPR3 inflammasome/IL-1β signaling and LDL transcytosis. Using optimized cationic liposomes to encapsulate methylated NLRP3 siRNA, resulting in targeting of VCAM-1-expressing ECs, to knockdown NLRP3, TNF-α-induced NLRP3 inflammasome activation and LDL transcytosis were prevented. Using the partial carotid ligation as an atherosclerosis rat model, we found that local administration of NLRP3 siRNA-PCLs efficiently knocked down NLPR3 expression in the carotid endothelium and dramatically attenuated the deposition of atherogenic LDL in carotid ECs in TNF-α-challenged rats. Furthermore, NLRP3 siRNA-PCLs were injected intravenously in ApoE−/− mice, resulting in reduced plaque formation. ConclusionThese findings established a novel strategy for targeting the NLRP3 inflammasome using NLRP3 siRNA-PCLs to interrupt LDL transcytosis, representing a potential novel therapy for atherosclerosis.

Anti-atherosclerotic Effects of Myrtenal in High-Fat Diet-Induced Atherosclerosis in Rats

The major cause of death worldwide is atherosclerosis-related cardiovascular disease (ACD). Myrtenal was studied to determine control rats were given standard diets and a high-fat diet was given to AS model groups. Atherosclerosis-related cardiovascular disease (ACD) is globally attributed to being a predominant cause of mortality. While the beneficial effects of Myrtenal, the monoterpene from natural compounds, are increasingly being acknowledged, its anti-atherosclerotic activity has not been demonstrated clearly. The present study is proposed to determine the anti-atherosclerotic activity of Myrtenal in high-fat diet-induced atherosclerosis (AS) rat models. Control groups were maintained with standard diets, the AS model rats were provided a high-fat diet, two of the experimental groups fed with a high-fat diet were treated with Myrtenal (50mg/kg and 100mg/kg), and one experimental group on high-fat diet was treated with simvastatin (10mg/kg) for 30days. The levels of inflammatory cytokines were analyzed using kits. The lipoproteins and the lipid profile were estimated using an auto-analyzer. The atherogenic index and marker enzyme activities were also determined. Serum concentrations of 6-keto-prostaglandin F1α (6-keto-PGF1α), thromboxaneB2 (TXB2), endothelin (ET), and nitric oxide (NO) were measured. The AS model groups indicated altered lipid profile, lipoprotein content, atherogenic index, calcium levels, HMG-CoA reductase activity, collagen level, and mild mineralization indicating atherosclerosis, while the AS-induced Myrtenal-treated groups demonstrated anti-atherogenic activity. The Myrtenal-treated groups exhibited a decreased TC, TG, and LDLc levels; increased HDLc levels; and a decline in the inflammatory cytokines such as CRP, IL-1β, IL-8, and IL-18 when compared to the untreated AS rats. Furthermore, Myrtenal decreased ET, TXB2, and 6-keto-PGF1α levels indicating its anti-atherosclerotic activity. The study results thus indicate that Myrtenal modulates the lipid metabolic pathway to exert its anti-atherosclerotic activity.

Effect of bortezomib on fatty liver in a rat model of atherosclerosis

Introduction and Aim: Fatty liver is associated with atherosclerosis even though the exact mechanism remains unknown. Fatty liver and atherosclerosis correlate with inflammation. Interleukin 6 (IL-6) is recognized as an inflammatory marker. Bortezomib is a proteasome inhibitor that will inhibit the proteasome pathway and is expected to inhibit inflammation in atherosclerosis. The current research aimed to investigate the effect of bortezomib on the fatty liver of atherosclerosis rats and to analyze its correlation with serum IL-6 concentration. Materials and Methods: Experimental subjects were 18 male Wistar rats (Rattus novergicus) divided into three treatment groups, namely atherosclerosis group (I), atherosclerosis + bortezomib group (II), and control group (III). Bortezomib (50 ?g/kg BW) was given twice intraperitoneally, on day 1 and day 3. The presence of fatty liver was evaluated using the percentage system. Serum IL-6 concentrations were measured using enzyme-linked immunosorbent assay kits. Results: The highest amount of fatty liver was found in the atherosclerosis group (group I) (38.33%), while the lowest was in the control group (group III) (5.83%). There was a decreasing fatty liver percentage due to bortezomib administration (group II) (29.17%), and it was statistically significant. There is a significant correlation between the degree of fatty liver and serum IL-6 concentration. Conclusion: The administration of bortezomib 50 ?g/kg BW in atherosclerosis model rats can reduce the occurrence of fatty liver by reducing the inflammatory process.

Anti-atherosclerotic activity of aqueous extract of Ipomoea batatas (L.) leaves in high-fat diet-induced atherosclerosis model rats.

Cardiovascular diseases, especially atherosclerosis, are the leading cause of human mortality in Indonesia. Ipomoea batatas (L.) is a food plant used in Indonesian traditional medicine to treat cardiovascular diseases and related conditions. We assessed the anti-atherosclerotic activity of the aqueous extract of I. batatas leaves in a rat model of high-fat diet-induced atherosclerosis and its mechanism. The presence of amino acid content in the I. batatas L. purple variant was determined by liquid chromatography high-resolution mass spectrometry (LC-HRMS). Thirty male Wistar rats were divided into five groups (n=6/group), i.e., standard diet group (SD), high-fat diet group (HF), and HF plus I. batatas L. extracts orally (625; 1,250; or 2,500mg/kg) groups. The numbers of macrophages and aortic wall thickness were analyzed histologically. Immunohistochemical analyses were performed to assess foam cells-oxidized low-density lipoprotein (oxLDL), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor (VEGF) expression in the aorta. LC-HRMS analysis showed nine amino acid content were identified from I. batatas L. In vivo study revealed that oral administration of I. batatas L. leaf extract alleviated foam cells-oxLDL formation and aortic wall thickness caused by high-fat diet atherosclerosis rats. Further, I. batatas L. leaf extract promoted the number of macrophages and modulated VEGF and eNOS expression in the aorta. I. batatas L. leaf extract shows a positive anti-atherosclerosis effect. Furthermore, the mechanism may promote the macrophages, eNOS, VEGF expressions, and inhibition of foam cells-oxLDL formation and aortic wall thickness with the best dosage at 2,500mg/kg. This could represent a novel approach to prevent cardiovascular diseases.

Anti-Atherosclerosis and Anti-Hypertensive Effects of Flavonoid Isorhamnetin Isolated from the Bark of Cordia dichotoma L

Aims: This study aimed to investigate the anti-atherosclerotic and anti-hypertensive ability of isolated Isorhamnetin from the bark of Cordia dichotoma L.&#x0D; Study design: Experimental study&#x0D; Place and Duration of Study: The extraction and isolation of bark of Cordia dichotoma L bark (ACDL) was done at Biosapience lab, Bhopal, India. Anti-atherosclerotic activity was done at IFTM University, Moradabad, India. Anti-hypertensive activity was done at BilwalMedchem and Research Laboratory, Pvt. Ltd, Jaipur, India. All the studies was conducted from 2015 to 2021 depending upon the availability of resources.&#x0D; Methodology: Column chromatography was done for Ethyl acetate soluble fraction of successive alcoholic extract of Cordia dichotoma L bark (ACDL), followed by successive fractionation using benzene, n-butanol, and acetone. Eluents with similar Rf values were pooled and underwent flavonoid test. Only a single eluents that passed the test was underwent purification. The crystallized powder obtained underwent UV, FTIR, Mass, 1H NMR and 13C NMR analysis for structural identification.&#x0D; The evaluation of anti-atherosclerotic activity of isolated Isorhamnetin from bark extract of plant C. dichotoma L was done in high fat induced atherosclerosis rats. The seven groups of Wistar rats were taken and each group containing six rats. To evaluate the anti-hypertensive activity of the plant extract, L-NAME induced hypertension model was used.&#x0D; Results: The structural identification and confirmation of flavonoid Isorhamnetin was analyzed by characterizations of isolated product. Lipid, lipoprotein profile and body weight were determined in high fat diet induced atherosclerosis rats. Isorhamnetin isolated from bark of C. dichotoma L produced a significant and dose-dependent anti-atherosclerotic activity in terms of reduction in low density lipoprotein (LDL), very low density lipoprotein (VLDL), Total cholesterol (TC), and Triglyceride (TG) level; and elevation of high density lipoprotein (HDL). Isorhamnetin isolated from the bark of plant C. dichotoma L reduced the elevated arterial pressure of L-NAME induced hypertensive rat significantly to the level of normotensive animal group. The isolated Isorhamnetin have shown its potential as an efficient source for the treatment of hypertension.&#x0D; Conclusion: The present study has identified the isolation and characterization of isorhamnetin flavonoid from bark of plant C. dichotoma L. This study also provides evidences of anti-atherosclerotic and antihypertensive effects of C. dichotoma L.

Verbascoside inhibits the progression of atherosclerosis in high fat diet induced atherosclerosis rat model.

Atherosclerosis is thickening of arterial wall, which causes several complications. This study evaluated the protective effect of verbascoside against atherosclerosis and the potential molecular mechanism involved. Atherosclerosis was induced by administering a high-fat diet to rats for 3 months and vitamin D3 for 4 days. Verbascoside (2 mg/kg p.o.) was administered for 6 weeks after the end of high-fat diet administration. The serum levels of inflammatory mediators and the lipid profile were determined, and atherosclerotic lesions were observed via Sudan IV staining. Moreover, immunohistochemical analysis, Western blot assay and qRT-PCR were performed to determine the effect of verbascoside on the AMPK/mTOR pathway in atherosclerosis. The results reveal that verbascoside ameliorated the altered serum levels of inflammatory mediators and the lipid profile as well as the organ coefficients in the atherosclerotic rats. A significant decrease in atherosclerotic lesions was detected in the verbascoside-treated group than the atherosclerosis group. AMPK and mTOR mRNA expression decreased in aortic tissues of the verbascoside-treated group compared to the atherosclerosis group. These data suggest that verbascoside ameliorates atherosclerosis by decreasing hyperlipidaemia in atherosclerosis induced by a high-fat diet.

Urantide alleviates the symptoms of atherosclerotic rats in vivo and in vitro models through the JAK2/STAT3 signaling pathway

Atherosclerosis is the leading cause of human death, and its occurrence and development are related to the urotensin II (UII) and UII receptor (UT) system and the biological function of vascular smooth muscle cells (VSMCs). During atherosclerosis, impaired biological function VSMCs may promote atherosclerotic plaque formation. The Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway is an important mediator of signal transduction; however, the role of this signaling pathway in atherosclerosis and VSMCs remains unknown. This study aimed to investigate the effects of urantide on the JAK2/STAT3 signaling pathway in atherosclerosis. We examined the effect of urantide on the UII/UT system and the JAK2/STAT3 signaling pathway in a high fat diet induced atherosclerosis rat model and studied the effect and mechanism of urantide on the phenotypic transformation of VSMCs. We found that the UII/UT system and JAK2/STAT3 signaling pathway were highly activated in the thoracic aorta in atherosclerotic rats and in ox-LDL- and UII-induced VSMCs. After urantide treatment, the pathological changes in atherosclerotic rats were effectively improved, and the activities of the UII/UT system and JAK2/STAT3 signaling pathway were inhibited. Moreover, urantide effectively inhibited proliferation and migration and reversed the phenotypic transformation of VSMCs. These results demonstrated that urantide may control the JAK2/STAT3 signaling pathway by antagonizing the UII/UT system, thereby maintaining the biological function of VSMCs and potentially preventing and curing atherosclerosis.

Malondialdehyde (MDA) Production in Atherosclerosis Supplemented with Steamed Tomato.

Malondialdehyde (MDA) may increase influenced by free radicals due to lipid oxidation. Tomato induction considers able to prevent free radical damage and atherosclerosis. Therefore, this study aims to understand the effect of steamed-tomato extracts on MDA and its potential as an early diagnosis of atherosclerosis. A total of 24 healthy 12 weeks-old male-rats were divided into four treatment groups, equally. A normal control group (K1) was rats with placebo treatment. A negative control group (K2) was the rats supplemented with 2 mL kg-1 b.wt. per day of cholesterol until cholesterol. A K3 group was atherosclerosis rats given with 20 mg kg-1 b.wt. per day of atorvastatin and a K4 was atherosclerotic rats supplemented with 16 mg kg-1 b.wt. per day of tomato extract. All treatments were carried out for 60 consecutive days. Tomato extract in the K4 group was succeeded in lowering MDA production. Carotenoid compounds in tomato extract are well known to be prevention agents against lipid oxidation and inhibit free radicals. MDA levels have increased significantly in atherosclerosis conditions, making it potentially noticeable during early atherosclerotic, therefore, potentially developed as biomarkers. MDA levels increase significantly and simultaneously after high cholesterol diets and in line with lipid parameters and damaged blood vessels. The steamed-tomato extract can reduce MDA, lipids levels and protect endothelial from lipid oxidation. More research should be conducted to breakdown the MDA function in the molecular pathway, including MDA correlation to microRNA expression and cell signaling.