Histopathology Of Aorta Research Articles

Sorghum Tempeh on Cholesterol Levels and Histopathology of Aorta in High-Fat Diet-Induced Rat Model

Sorghum Tempeh on Cholesterol Levels and Histopathology of Aorta in High-Fat Diet-Induced Rat Model

Effect of sunkist orange peel nanoparticle granules on cardiac and aorta histopathology in diabetic rats

Sunkist oranges (Citrus sinensis (L.) Osbeck) is rich in anthocyanins (95% of which are represented by cyanidin-3-glucoside and cyanidin-3-6"-malonyl-glucoside), flavanones (hesperidin and narirutin), hydroxycinnamic acid, carotenoids, sugars, minerals, and fiber, which offer health benefits. This study aimed to evaluate the efficacy of sunkist orange peel nanoparticle granules on the histopathological appearance of the cardiac and aorta in alloxan-induced diabetic rats. This study used a post-test experimental design, with a control group. Twenty-five male Wistar rats were randomly divided into five groups: negative control (alloxan+distilled water), positive control (alloxan+metformin), treatment 1 (alloxan+granular nanoparticles 50 mg/kg BW), treatment 2 (alloxan+granular nanoparticles 70 mg/kg BW), and treatment 3 (alloxan+granular nanoparticles 100 mg/kg BW). The heart and aorta were prepared for observation using 10x ocular magnification and 40x objective lens magnification. Kruskal-Wallis statistical test results revealed a significant difference in the average cardiac histopathological score between the treatment groups (p = 0.011). The amount of aortic endothelial cell damage can be seen from the presence of foam cells in the K(-) treatment group, while the K(+), P1, P2, and P3 groups did not have foam cells in the aortic endothelium. The findings of this study indicate that sunkist orange peel extract nanoparticles in granular form improve cardiac and aortic histopathology, with a dose of 100 mg/kg BB being the best dose for improving cardiac and aortic histopathology.

The Lipid Profile and Aorta Histopathology On Hyperlipidemic Rat by Saurauia vulcani Korth. Leaves Extract

Abstract. Dyslipidemia is a pathological condition characterized by increased levels of total cholesterol, triglycerides and LDL and decreased levels of HDL. Dyslipidemia causes cardiovascular disease risk factors by increasing cholesterol levels, increasing triglyceride levels, lowering HDL levels, and increasing LDL levels, as well as decreasing the proliferation of cardiac aortic cells in dyslipidemic rats. The pirdot plant (Saurauia vulcani Korth.) has long been known by the Simalungun, Toba and Karo communities to have the potential to treat various diseases caused by disruption of lipid processes in the body. Pirdot leaves contain bioactive compounds of flavonoids, tannins and saponins that have the potential to improve lipid profiles and prevent cardiovascular disease. This study aims to determine the activity of EEDP on the lipid profile of dyslipidemic rats. Pirdot leaf simplicia powder was extracted by maceration with 96% ethanol solvent and the extract was used on 30 dyslipidemic rats which were divided into 6 groups. Group 1 (Na-CMC), group 2 (Atorvastatin), group 3, 4, 5, 6 EEDP doses of 50, 100, 200, 400 mg/kg BW were administered orally for 21 days. At the end of the treatment, the levels of total cholesterol (TC) and aortic cell proliferation were measured. The results showed that Saurauia vulcani Korth had water content (6.23%), water soluble extract (10.50%), simplicia content soluble in ethanol (14.77%), total ash content (7.05%) and acid insoluble ash content (0.48%). From the antidyslipidemic study it was shown that EEDP 400 mg/kg BW improved blood lipand to increase aortic cell proliferation dyslipidemic rats was 69.84±0.27. Based on the explanation above, it is concluded that EEDP has an antidyslipidemic effect.

Cigarette Smoke Exposure, but Not High Fat Diet, is Able to Induce Atherosclerosis in Wild-Type Rats

Background: High-fat diet (HFD) and cigarette smoke exposure (CSE) have been used to induce atherosclerosis in wild-type (WT) rats however, their effectivity remains unclear.Objective: To confirm and compare the effectivity of HFD and CSE on both the histopathology of aorta and the level of malondialdehyde (MDA) in WT rats.Methods: Thirty-six WT Wistar rats were divided into four main groups (K0, K1, K2, and K3) and four subgroups (K3A, K3B, K3C, and K3D). The negative control group (K0) was fed with regular diet. Group K1 was treated with an intravenous adrenaline followed by high-fat diet (HFD), K2 was fed with regular diet and given CSE, while K3 was treated with a combination of CSE and HFD. The serum and cardiac MDA levels were measured using ELISA. Hematoxylin eosin and oil red O staining of aorta were done for measuring of the intima-media thickness (IMT) ratio and for counting of foam cells, respectively. Results: Both serum and cardiac tissue MDA levels in either K1, K2, or K3 were significant higher (p<0.01) than that of in K0. IMT ratio in K3 was significant higher compared to other groups (p<0.01). Foam cell numbers were significant higher in K2 and K3 groups than that of in either K0 or K1 (p<0.01).Conclusion: While the HFD fails to induce atherosclerosis in WT rats for 28 days, either CSE or combination of CSE and HFD is able to induce it, and the combination is better than alone.

Human umbilical cord-derived mesenchymal stem cells not only ameliorate blood glucose but also protect vascular endothelium from diabetic damage through a paracrine mechanism mediated by MAPK/ERK signaling

BackgroundEndothelial damage is an initial step of macro- and micro-vasculature dysfunctions in diabetic patients, accounting for a high incidence of diabetic vascular complications, such as atherosclerosis, nephropathy, retinopathy, and neuropathy. However, clinic lacks effective therapeutics targeting diabetic vascular complications. In field of regenerative medicine, mesenchymal stem cells, such as human umbilical cord-derived MSCs (hucMSCs), have great potential in treating tissue damage.MethodsTo determine whether hucMSCs infusion could repair diabetic vascular endothelial damage and how it works, this study conducted in vivo experiment on streptozotocin-induced diabetic rat model to test body weight, fasting blood glucose (FBG), serum ICAM-1 and VCAM-1 levels, histopathology and immunohistochemical staining of aorta segments. In vitro experiment was further conducted to determine the effects of hucMSCs on diabetic vascular endothelial damage, applying assays of resazurin staining, MTT cell viability, wound healing, transwell migration, and matrigel tube formation on human umbilical vein endothelial cells (HUVECs). RNA sequencing (RNAseq) and molecular experiment were conducted to clarify the mechanism of hucMSCs.ResultsThe in vivo data revealed that hucMSCs partially restore the alterations of body weight, FBG, serum ICAM-1 and VCAM-1 levels, histopathology of aorta and reversed the abnormal phosphorylation of ERK in diabetic rats. By using the conditioned medium of hucMSCs (MSC-CM), the in vitro data revealed that hucMSCs improved cell viability, wound healing, migration and angiogenesis of the high glucose-damaged HUVECs through a paracrine action mode, and the altered gene expressions of IL-6, TNF-α, ICAM-1, VCAM-1, BAX, P16, P53 and ET-1 were significantly restored by MSC-CM. RNAseq incorporated with real-time PCR and Western blot results clarified that high glucose activated MAPK/ERK signaling in HUVECs, while MSC-CM reversed the abnormal phosphorylation of ERK and overexpressions of MKNK2, ERBB3, MYC and DUSP5 in MAPK/ERK signaling pathway.ConclusionsHucMSCs not only ameliorated blood glucose but also protected vascular endothelium from diabetic damage, in which MAPK/ERK signaling mediated its molecular mechanism of paracrine action. Our findings provided novel knowledge of hucMSCs in the treatment of diabetes and suggested a prospective strategy for the clinical treatment of diabetic vascular complications.

Differences in Aortic Histopathology in Patients Undergoing Valve Reimplantation Surgery for Various Clinical Syndromes.

Objectives The study aims to investigate aortic histopathologic differences among patients undergoing aortic valve reimplantation, suggest different mechanisms of aortic root aneurysm pathogenesis, and identify factors associated with long-term success of reimplantation. Methods From 2006 to 2017, 568 adults who underwent reimplantation for repair of aortic root aneurysm, including patients with tricuspid aortic valves with no connective tissue disease (TAV/NoCTD, n = 314/568; 55.3%), bicuspid aortic valves (BAVs, n = 86/568; 15.1%), or connective tissue disease (CTD, n = 177/568; 31.2%), were compiled into three comparison groups. Patients with both BAV and CTD ( n = 9/568; 1.6%) were omitted to increase study power. Patient records were analyzed retrospectively, focusing on pathology reports, which were available for 98.42% of patients, and were classified based on their descriptions of aortic tissue samples, primarily from the noncoronary sinus. Mean follow-up time available for patients was 2.97 years. Results Aortitis, medial fibrosis, and smooth muscle loss were more common histopathologic findings in patients with TAV/NoCTD than in patients with BAV and CTD ( p < 0.05). Cystic medial degeneration was most often found in patients with CTD, then TAV/NoCTD, and least in BAV ( p < 0.01). Increases in mucopolysaccharides were found more often in the BAV group than in the TAV/NoCTD and CTD groups ( p < 0.01). There were no differences in the frequency of elastic laminae fragmentation/loss across these three groups. Among all patients, 1.97% ( n = 11/559) had an unplanned reintervention on the aortic valve after reimplantation, but no significant demographic or histopathologic differences were identified. Conclusion Despite some common histopathologic features among patients undergoing aortic valve reimplantation, there were enough distinguishing features among aortic tissue samples of TAV/NoCTD, BAV, and CTD patients to suggest that these groups develop root aneurysms by different mechanisms. No histopathologic features were able to predict the need for late reintervention on the aortic valve.

Long-Term Safety and Durability of Novel Intra-Aortic Percutaneous Mechanical Circulatory Support Device

<h3>Purpose</h3> Intra-aortic percutaneous mechanical circulatory support (pMCS) devices have potential to safely treat pre-end stage heart failure patients by reducing cardiac afterload and increasing renal perfusion with no hardware in the left ventricle, across the aortic valve, or above the aortic arch. A challenge for home ambulatory use targeting indications such as bridge-to-recovery or bridge-to-transplant is achieving long-term durability and retrievability without design elements that constrain home use or reduce quality-of-life. <h3>Methods</h3> Intra-aortic pMCS devices were implanted in 4 sheep above the renal arteries by withdrawing the deployment sheath to allow expandable atraumatic struts to engage the aortic wall. The pumps required only electrical power and the 6 Fr power leads were tunneled and externalized on the animals' flanks. All animals were initially cross-tied and infused with heparin for several days before switching to subcutaneous enoxaparin and being allowed to roam their pens. The pumps operated with vest mounted controllers and 1-pound, smart-phone-sized, 10-hour batteries. Study outcomes were pump durability, thrombus formation, hemolysis, operating uptime, and targeted necropsy with histopathology performed by independent laboratory staff. <h3>Results</h3> Pumps operated for 90-142 days limited only by animal activity (snagging, chewing) that pulled 3 of 4 pumps from their initial position; 2 were pulled into the femoral artery and 1 remained super renal. The remaining animal was electively sacrificed at 142 days. Pump flow was blocked in one of the pumps pulled into the femoral artery and minor thrombus was observed at necropsy. The other 3 pumps were thrombus free and appeared unchanged from implant. No pumps showed any degree of adhesion between the struts and the aortic wall. Bearing surfaces on all pumps showed minimal wear consistent with those from pumps run for only 7 days <i>in vivo</i>. There was no clinically significant hemolysis. Aorta histopathology revealed no device-related trauma, endothelialization, or adhesion. Kidney histopathology showed no pump-related findings. <h3>Conclusion</h3> Safe, long-term use of the intra-aortic pMCS device has been demonstrated in a preclinical model. With no significant findings in bearing wear, pump/tissue interface, or end organs, home ambulatory use of this type of system for 6 to 12 months appears feasible.

Assessment of Computational Histopathology in Thoracic Aortic Aneurysm

Background and Hypothesis: Thoracic aortic aneurysm (TAA) histopathology includes elastic fiber (EF) abnormalities, mucoid extracellular matrix (MECM) accumulation, and smooth muscle derangement in the aortic medial layer. While semi-quantitative grading of these characteristics is a standard practice, computational characterization of medial layer components may facilitate novel quantitative analyses at higher throughput. We hypothesized that computational results would correlate with results of semi-quantitative grading of aortic histopathology.&#x0D; Experimental Design: Formalin-fixed, paraffin-embedded human aortic tissue sections were stained with Movat’s pentachrome to characterize aortic microstructure. Sections were also immunostained for nitrotyrosine residues to assess oxidative stress. Samples were initially graded semi-quantitatively by two independent blinded readers. Next, computational histopathology software was used a) to quantify the proportions of EF, MECM, and cellular area in the medial layer of pentachrome-stained sections and b) to quantify the distribution and intensity of positive nitrotyrosine staining in immunostained sections. Association between semi-quantitative grading and computed values was tested with ANOVA.&#x0D; Results: The cohort included 74 participants who underwent prophylactic aortic replacement for TAA and 23 healthy controls. The mean age was 54±17 years. On average, EFs accounted for 49% (range 6-90%) of medial tissue area, whereas MECM accounted for 25% (1-73%). The overall semi-quantitative grade of medial degeneration severity was associated with decrease in EF fraction (p=0.02). The grade of EF thinning also strongly correlated with decrease in EF fraction (p=1x10-6). Meanwhile, grade for accumulation of MECM was associated with increase in MECM (p=0.004). Increased semi-quantitative grading for nitrotyrosine levels was associated with increased nuclear signal optical density (p=9x10-10) and greater percentage of cells labeled as strongly positive (p=8x10-10).&#x0D; Conclusion and Potential Impact: We observed significant correlations between computed quantitative values and semi-quantitative grading. This suggests that computational histopathology is a valid method for investigation of human TAA tissues.

Effects of Alcoholic Extracts of Bangladeshi Mangrove Acanthus ilicifolius Linn. (Acanthaceae) Leaf and Stem on Atherogenic Model of Wistar Albino Rats.

Acanthus ilicifolius Linn. (Acanthaceae) is a popular mangrove ethnomedicinal plant that cures several ailments, including asthma, diabetes, cancer, and many others. Our experiment was aimed at evaluating the anti-atherogenic effect of A. ilicifolius (leaf and stem) on a high-fat diet-induced atherogenic rat model. Atherosclerosis was developed in 12 weeks. Treatment with the standard drug (3 mg/kg b.w./day, p.o. of Simvastatin), separate doses of methanolic and ethanolic extracts of A. ilicifolius leaf (250 and 500 mg/kg b.w./day, p.o.), and stem (200 and 400 mg/kg b.w./day, p.o.) was subsequently conducted for additional 15 days. The anti-atherogenic effect was evaluated by estimating the change in body weight, systolic blood pressure, and lipid profile. Histopathology of aorta, liver, and kidney of atherogenic models was done for further evaluation. The antioxidant effect of different extracts was performed via DPPH (2,2-diphenyl-1-picrylhydrazyl) assay using ascorbic acid as standard. The anticoagulant effect was determined after 15 days of treatment with the same doses of the plant extracts and the standard Warfarin (2 mg/kg b.w./day, p.o.). When compared with atherogenic control, treatment with A. ilicifolius significantly reduced (p < 0.01) body weight, systolic blood pressure, and serum lipid levels while it elevated HDL (high-density lipoprotein) level in a dose-dependent manner. Moreover, bleeding and clotting time was significantly decreased (p < 0.01) under the treatment of plant extracts. The histopathological data showed considerable improvement in tissue morphology after treatment. Our study evidenced that the alcoholic extracts of A. ilicifolius leaf and stem have anti-atherogenic properties and may be recommended as a potential herbal remedy for preventing cardiovascular diseases.

Effect of Bortezomib on Total Cholesterol, Triglycerides and Histopathology Abdominal Aorta in Rats of Atherosclerosis Model

The effects of using proteasome inhibitors on atherosclerosis could be beneficial or detrimental. This study aimed to analyze the effects of proteasome inhibitors in the progression stage. Experimental animals (18 rats) were divided into three groups, namely control (C) as a group of rats given standard feed, P1 as atherosclerosis-induced rat group, and P2 as atherosclerosis-induced rat group and given proteasome inhibitors. Proteasome inhibitor administered was bortezomib at a dose of 50µg/kgBW/day intraperitoneally on day 1 and 3. After four days of treatment, the termination and measurement of serum total cholesterol, serum triglycerides, and abdominal aorta histopathology with hematoxylin-eosin staining were carried out. Serum total cholesterol levels were measured using the CHOD-PAP (Cholesterol Oxidase-Peroxidase Aminoantypirin) method, whereas serum triglyceride levels were measured using the GPO-PAP (glycerol phosphatase oxidase−phenol4-amino antipyrene peroxidase) method. Histopathological assessment was carried out with a scoring system in 9 fields of view with a 400x magnification, which was then averaged. The ANOVA test showed significant differences in serum total cholesterol, serum triglycerides, and abdominal aortic histopathology between atherosclerosis and control groups, but there were no significant differences in the administration of bortezomib in atherosclerosis except in serum triglyceride levels. It can be concluded that the administration of 50µg/kg bortezomib for four days in the rats model of the progression stage of atherosclerosis can decrease serum triglyceride levels, although it can not inhibit the formation of atherosclerotic lesions and has no effect on serum total cholesterol.Â

The potency of green grass jelly extract (Premna oblongifolia Merr) as antihyperlipidemia towards aorta histopathology representation of rat (Rattus norvegicus) induced with high fatty diet (HFD)

Green grass jelly (Premna oblongifolia merr) is a plant containing fiber and chlorophyll which can lower cholesterol and triglyceride levels. This study have aims to investigate the potency of green grass jelly extract (Premna oblongifolia Merr) to prevent hyperlipidemia. The animal mode used for this study is male Rattus norvegicus, Wistar strain, the age of 8 weeks, and weight of 200 g which is divided into 5 groups of treatment namely group Kn (negative control), Kp (positive control), Kp1, Kp2, and Kp3 induced with HFD and green grass jelly extract at a dose of 5.27 g/ kg BW/ daily, 8.43 g/ kg BW/ daily, 9.37 g/ kg BW/ daily. The data of infiltrating fatty cells and macrophage on aorta histopathology was analyzed by description. This research showed that the treatment of green grass jelly extract (Premna oblongifolia Merr) to animals of hyperlipidemia model reduced infiltration fatty cells and macrophage. The conclusion of this study was the green grass jelly extract was able to prevent an increase of fatty cells and macrophage infiltration of rat (Rattus noervegicus) induced with HFD on dose 9.37 g/ kg/ BW/ daily.

Exploration in the mechanism of rhubarb for the treatment of hyperviscosity syndrome based on network pharmacology

Ethnopharmacological relevanceHyperviscosity syndrome (HVS) is a major risk factor for thrombotic diseases. Rhubarb, well-known as a traditional Chinese medicine, exhibits multiple pharmacological activities, especially for promoting blood circulation to remove blood stasis (PBRB), which has been become a functional health food for decreasing the risk of cardiovascular diseases. However, due to the complexity of rhubarb components, it is still difficult to clarify the specific targets of effective substances in PBRB, and the pharmacodynamic mechanism needs to be further probed. Materials and methodsThe “compound-target-cell-disease” network analysis was initially used to predict potential targets and bioactive compounds. The effect of rhubarb for the treatment of HVS was examined by histopathology and biochemical assays based on the HVS rat model. ResultsThrough the “compound-target-cell-disease” network analysis, eight potential therapeutic targets were eventually screened out, and platelets were predicted as the main effector cells of rhubarb in PBRB. Among targets coagulation factor II (prothrombin, F2) and fibrinogen gamma chain (FGG) were closely related to platelets, and five compounds associated with F2 and FGG were predicted including emodin-8-O-beta-D-glucopyranoside (Emo), physcion-8-O-beta-D-glucopyranoside (Phy), procyanidin B-5,3′-O-gallate, torachrysone-8-O-beta-D-(6′-oxayl)-glucoside and epicatechin. Furthermore, thoracic aorta histopathology and biochemical examinations showed middle dose of rhubarb (0.42 g/kg/day) significantly ameliorated pathological changes, hemorheology parameters, as well as levels of representative biomarkers such as plasma P-selectin (P-sel) and thromboxane (TXB2) in platelet activation compared to HVS rat model, whose effects were comparable to the positive drug aspirin or even better. Finally, it was further validated F2 and FGG as the major effective targets of rhubarb as well as its two active ingredients Emo and Phy in PBRB. ConclusionsThis study may provide an innovative way and scientific information to further understand the main effective components of rhubarb and its mechanisms about targets of F2 and FGG in PBRB, especially the new therapeutic target FGG, which also provide a basis for establishing a quality control for rhubarb by bioassays that could correlate the clinical efficacy and its mechanism.

Curcumin incorporated titanium dioxide nanoparticles as MRI contrasting agent for early diagnosis of atherosclerosis- rat model

MRI is an excellent diagnostic technique for atherosclerosis in a non-invasive manner. Application of contrasting agents can improve its contrast through ionic properties. Macrophages and foam cells produce MCP-1 antibody, the sign of development of atherosclerosis. The work aims to develop novel curcumin incorporated titanium dioxide nanoparticles (CTNPs) conjugated with MCP-1 antibody with the specific targeting capability to macrophage-foam cells as contrasting agent for MRI. In vivo toxicity studies of Curcumin, TNPs and CTNPs were also done in Sprague dawley rats by GGT and ALP assays and found to be normal in comparison with control. Histopathology of aorta confirmed that the compound could not elicit a toxic effect in the target organ. Rats were fed with a high cholesterol diet to develop atherosclerotic foam cells and confirmed by Sudan IV staining and serum cholesterol level. CTNP-MCP-1 was injected into animals through tail vein and MRI scanning was done, gave contrasting images of atherosclerotic aorta in comparison with normal. Thus CTNPs can be used as a cost-effective contrasting tool for diagnosis of atherosclerosis at early stages in view of clinical imaging.

Anti-atherosclerotic effect of herbal extracts in N(G)-nitro-L-arginine methyl ester-treated rats

This study aimed to evaluate the anti-atherosclerotic and anti-hypertensive effects of six different plant extracts using a N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced rat model of hypertension. All extracts were administered orally for six weeks. At the end of the study period blood pressure, blood flow, aortic histopathology, and hepatic endothelial nitric oxide synthase (eNOS) expression were measured. Subsequently, we also measured the levels of intracellular reactive oxygen species, nitric oxide (NO), and anti-inflammatory cytokines in vitro. Based on these screening results, we selected extracts of Cinnamomum cassia (C. cassia) and Salvia miltiorrhiza (S. miltiorrhiza) for further evaluation. C. cassia and S. miltiorrhiza extracts ameliorated hypertension and atherosclerosis in L-NAME-treated rats in a dose-dependent manner. In addition, a mixture of C. cassia and S. miltiorrhiza had an additive effect to reduce blood pressure, increase blood flow, and normalize aortic tissue. This mixture demonstrated anti-oxidative and anti-inflammatory activities in vitro. In conclusion, although further analysis of the therapeutic mechanism is required, the anti-hypertensive and anti-atherosclerotic effects of this mixture are likely mediated by increased eNOS expression, and its anti-oxidative and anti-inflammatory activities.

The Effect of Dayak Onion Bulb Ethanol Extract (Sisyrinchium palmifolium L.) on Triglyceride Level and Aorta Histopathology in Diabetes Melitus White Rat Induced by Alloxan

The high prevalence of diabetes mellitus in Indonesia has made antidiabetic treatment efforts increasingly popular. In addition, the many side effects caused by the use of chemical drugs, triggered the development of research on herbal therapy. The purpose of this study was to determine the effectiveness of Dayak onion bulb extract in reducing two-hour postprandial blood glucose, triglyceride levels, and the amount of lipid vacuoles in aorta blood vessels of diabetic rat. The long-term goal of this study is the creation of innovation products in the form of standardized herbs as complementary therapies that can be used daily by the community, so that the risk of morbidity can be reduced. The research design used was randomized control group pretest posttest design. The results of blood glucose analysis showed that there were significant differences between the positive control group with the 400 mg/KgBW and 800 mg/KgBW extract group, with a significance value of 0,000. In the extract group, 400 mg/KgBW with 800 mg/KgBW extract group showed no significant difference with a significance value of 0.390. The results of the analysis of triglyceride levels showed no significant difference between the positive control group with the 400 mg/KgBW extract group, with a significance value of 0.981. However, there were significant differences between the positive control group with the 800 mg/KgBW extract group with a significance value of 0.025. Between the 400 mg/KgBW and 800 mg/KgBW extract groups, there was a difference with a significance value of 0.024. Aorta histopathology results showed that there was a significant difference in the number of lipid vacuoles between the positive control group and the 400 mg/KgBW extract group and 800 mg/KgBW extract group. Based on the research, it can be concluded that the extract dose of 400 mg/KgBW is a dose that is able to influence the decrease in blood glucose levels, triglycerides and the amount of lipid vacuoles in the aorta blood vessels.

Evaluation of Combination of Low Dose Atorvastatin plus Ezetimibe and Aspirin in the Treatment of Atherosclerotic Vascular Disease

Objective: To evaluate the effect of combination of low dose of atorvastatin plus ezetimibe and aspirin in the treatment of Atherosclerotic Vascular Disease (AVD) with special emphasis on rhabdomyolysis. Experimental Design: Thirty male rats were allocated to five groups as normal control, disease control, and test groups I, II, III. All groups except normal control group received high fat diet for 10 weeks and treatment was initiated in test groups after the completion of 4th week, after rise in lipid levels and bodyweight of the rats when compared with normal control rats was noted. Normal control and disease control group animals received vehicle and test groups were treated with ezetimibe, 0.986mg/kg (Clinical dose 10 mg) and aspirin, 7.708mg/kg (Clinical dose 75 mg) along with differential doses of atorvastatin per orally. Test groups I, II, III received atorvastatin dose of 1.027mg/kg, 0.770mg/kg, 0.513mg/kg p.o. respectively which were equal to clinical doses of 10mg, 7.5mg and 5 mg of atorvastatin respectively. Body weight, lipid profile and grip strength were evaluated biweekly and histopathology of aorta was carried out at the end of the study. Results: The results of study reveal that test group II had significantly decreased the increased body weight, lipid levels, accumulation of lipids on the walls of aorta and incidence of rhabdomyolysis. Conclusion: The study demonstrates that atorvastatin at clinical dose of 7.5 mg have shown a decrease in the incidence rhabdomyolysis without loss of hypolipidemic activity when given along with clinical doses of ezetimibe and aspirin in the management of AVD. Key words: Atherosclerotic Vascular Disease, Atorvastatin, High Fat Diet Model, Rhabdomyolysis, Statins.

Effects of atorvastatin and diet interventions on atherosclerotic plaque inflammation and [18F]FDG uptake in Ldlr−/−Apob100/100 mice

Background and aimsUptake of the positron emission tomography (PET) tracer 2-deoxy-2-[18F]-fluoro-d- glucose ([18F]FDG) into macrophages is a sensitive marker of inflammation in atherosclerosis. To assess the anti-inflammatory effects of statins, we studied whether atorvastatin therapy reduces aortic [18F]FDG uptake in hypercholesterolemic mice deficient in low-density lipoprotein receptor (Ldlr), and expressing only apolipoprotein B-100 (Ldlr−/−Apob100/100). MethodsThirty-six Ldlr−/−Apob100/100 mice were fed a high-fat diet (HFD) for 12 weeks and then allocated to receive a HFD (n = 13), chow diet (Chow, n = 12), or HFD with added atorvastatin (HFD + A, n = 11), for another 12 weeks. In addition to aortic histopathology, [18F]FDG uptake was studied in vivo using PET/computed tomography (CT), and ex vivo by gamma counting of excised aorta. ResultsTotal cholesterol levels were lower in the Chow and HFD + A groups than in the HFD group (10 ± 3.2, 23 ± 4.9 and 34 ± 9.2 mmol/l, respectively), with the Chow group also showing a lower plaque burden and lower numbers of macrophages in the lesions. Compared to the HFD group, [18F]FDG uptake in the aorta (normalized for blood) was lower in the Chow group in both in vivo (2.1 ± 0.21 vs. 1.7 ± 0.25, p = 0.018) and ex vivo (5.2 ± 2.3 vs. 2.8 ± 0.87, p = 0.011) analyses, whereas atorvastatin had no effect on uptake (2.1 ± 0.42 in vivo and 3.9 ± 1.8 ex vivo). [18F]FDG uptake correlated with plasma total cholesterol levels. ConclusionsAtorvastatin therapy did not show cholesterol-independent effects on inflammation in atherosclerotic lesions in Ldlr−/−Apob100/100 mice, as determined by histology and [18F]FDG PET, whereas a cholesterol-lowering diet intervention was effective.

Improvement in erectile function in a rat model of high cholesterol diet-induced atherosclerosis by atorvastatin in a manner that is independent of its lipid-lowering property.

The purpose of the present study is to explore the effects of a lipid-lowering drug atorvastatin, a three-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, in the treatment of erectile dysfunction (ED) in a rat model of atherosclerosis (AS) and the possible mechanisms underneath. A high-cholesterol diet was administrated to Sprague-Dawley rats in an attempt to induce an ASED model, which was later confirmed by abdominal aorta histopathology and erectile function evaluation. ASED rats were further assigned to non-treatment group, atorvastatin low-dose treatment group (5mgkg-1 day-1 ), high-dose group (10mgkg-1 day-1 ) and sildenafil (1.5mgkg-1 day-1 ) treatment group. Lipid profile, erectile function, oxidative stress biochemical markers, endothelial nitric oxide synthase (eNOS) and extracellular superoxide dismutase (SODEX ) mRNA expression were evaluated after 8-week treatment duration. Erectile function was impaired in AS rat model, which was preserved in atorvastatin and sildenafil intervention groups. The oxidative stress biochemical markers were attenuated, while eNOS and SODEX mRNA expression were restored in atorvastatin and sildenafil groups, which were found to be involved in ED pathogenesis. However, the lipid profile remained unaltered in the treatment group, and it was elevated in ASED rats. This kind of lipid-lowering agent, or atorvastatin, has the utilisation potential in ASED treatment, even before lipid profiles altered. This effect on erectile function preservation of atorvastatin was attributed to its preservation of endothelial function, possibly through amelioration of oxidative stress and improvement in eNOS expression.

Sodium thiosulfate protects brain in rat model of adenine induced vascular calcification

Vascular bed calcification is a common feature of ends stage renal disease that may lead to a complication in cardiovascular and cerebrovascular beds, which is a promoting cause of myocardial infarction, stroke, dementia and aneurysms. Sodium thiosulfate (STS) due to its multiple properties such as antioxidant and calcium chelation has been reported to prevent vascular calcification in uremic rats, without mentioning its impact on cerebral function. Moreover, the previous studies have not explored the effect of STS on the mitochondrial dysfunction, one of the main pathophysiological features associated with the disease and the main site for STS metabolism. The present study addresses this limitation by using a rat model where 0.75% adenine was administered to induce vascular calcification and 400 mg/kg b wt. of STS was given as preventive and curative agent. The blood and urine chemistries along with histopathology of aorta confirms the renal protective effect of STS in two modes of administration. The brain oxidative stress assessment was made through TBARS level, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, found to be in the near normal level. STS administration not only reduced the mitochondrial oxidative stress (measured by TBARS, SOD, GPx and CAT) but also preserved the mitochondrial respiratory enzyme activities (NADH dehydrogenase, Succinate dehydrogenase and Malate dehydrogenase) and its physiology (measured by P/O ratio and RCR). In fact, the protective effect of STS was prominent, when it was administered as a curative agent, where low H2S and high thiosulfate level was observed along with low cystathionine β synthase activity, confirms thiosulfate mediated renal protection. In conclusion, STS when given after induction of calcification is protective to the brain by preserving its mitochondria, compared to the treatment given concomitantly.

PP.13.15

Objective: Hypercholesterolemia can cause damage to the artery before the atherosclerotic lesion has formed. Intermedin (IMD) is a novel member of the calcitonin gene-related peptide family. Endogenous IMD is reported to participate in several cardiovascular pathological states. Using the rats fed with high-cholesterol diet, this study aims to investigate the aortic expression of IMD and its receptors in hypercholesterolemia without atherosclerosis. Furthermore, by the antioxidant intervention, we also explore the influence of oxidative stress. Design and method: Male Wistar rats were fed with high cholesterol diet, with or without concurrent administration of simvastatin and vitamin C. The serum lipid levels were measured, and the aortic histopathology features were examined. Both the malondialdehyde (MDA) and superoxide dismutase (SOD) in plasma and aorta were determined as the oxidative stress biomarkers. The plasma IMD was assessed by radioimmunoassay. Within the aorta, the mRNA expression of IMD along with its receptor components were determined by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), and the corresponding protein level of the CRLR/RAMPs were assessed by Western blot analysis. Results: The hypercholesterolemia rats without atherosclerotic lesion manifested higher level of MDA and SOD. The IMD in plasma was elevated. Within the aorta, increased expression of IMD and all its receptor components (CRLR, RAMP1, RAMP2, and RAMP3) were displayed. The simvastatin indirectly attenuated oxidative stress by improving lipid profiles, while the vitamin C directly reduced oxidative stress without interfering with the serum lipids. Both simvastatin and vitamin C ameliorated the aortic injury, decreased the plasma IMD level, and recovered the expression of IMD and its receptors within the aorta. Conclusions: For the first time, the up-regulated expression of IMD is observed within the aorta of the hypercholesterolemia rats, demonstrating the pathophysiological role which IMD has performed in hypercholesterolemia absent of atherosclerosis lesion. In addition, the oxidative stress is evidenced to participate in the up-regulation.