Atherosclerosis Model Group Research Articles

Effect of L-Arginine on Lipid Metabolism and Morphology of Cardiomyocytes of Animals with Experimental Atherosclerosis in High-Altitude Conditions

Background: The Kyrgyz Republic, with its high-altitude regions, poses unique health challenges due to extreme geoclimatic factors. Cardiovascular disease (CVD) is prevalent in the region, and dyslipidemia, a significant risk factor for atherosclerosis and CVD, is associated with elevated serum cholesterol levels. This study investigates the effects of high-altitude environments on human health and the potential therapeutic benefits of L-arginine in regulating carbohydrate and lipid metabolism. Materials and Methods: Thirty rabbits were divided into five groups: Control (low-altitude), high-altitude (3 days), atherosclerosis model, atherosclerosis with preventive L-arginine and cholesterol treatment, and atherosclerosis with L-arginine treatment. Atherosclerosis was induced by oral cholesterol administration (500 mg/kg/day) for 60 days. L-arginine (170 mg/kg/day) was administered for 30 days for treatment and prevention. Lipid metabolism indicators (high-density lipoprotein, low-density lipoproteins, triglycerides, and total cholesterol [TC]) were measured using a biochemical autoanalyzer. Histological examination of excised plaques and myocardial morphology was performed. Results: Results showed a significant reduction in TC levels in the high-altitude group compared to the control. The atherosclerosis model group exhibited a tenfold increase in TC, which remained unchanged with preventive L-arginine and cholesterol treatment. However, L-arginine treatment alone decreased TC levels by approximately 65%, although still twice as high as the control. Conclusion: The findings suggest that L-arginine may have potential therapeutic benefits in regulating lipid metabolism and improving cardiomyocyte morphology in rabbits with induced atherosclerosis under high-altitude conditions.

Serum tsncRNAs reveals novel potential therapeutic targets of Salvianolic Acid B on atherosclerosis

BackgroundSalvianolic Acid B (SalB) has been proven to delay the progression of atherosclerosis. The therapeutic mechanisms of this compound are unclear. A novel class of short non-coding RNAs, pre-transfer RNA and mature transfer RNA (tsncRNAs) may regulate gene expression. TsncRNAs-sequencing revealed novel therapeutic targets for SalB. This is the first study focusing on tsncRNAs to treat atherosclerosis using SalB. PurposeTo explore the potential mechanism of SalB treating atherosclerosis through tsncRNAs. MethodsFive groups of mice were created at random: control group (CON), atherosclerosis model group (MOD), SalB with high dose-treated group (SABH), SalB with low dose-treated group (SABL), and Simvastatin-treated group (ST). Aortic sinus plaque, body weight and inflammatory cytokines were evaluated. The Illumina NextSeq equipment was used to do expression profiling of tsncRNAs from serum. The targets of tsncRNAs were then predicted using tRNAscan and TargetScan. The KEGG pathway and GO analysis were utilized to forecast the bioinformatics analysis. Potential tsncRNAs and associated mRNAs were validated using quantitative real-time PCR. ResultstRF-Glu-CTC-014 and tRF-Gly-GCC-074 were markedly increased by SalB with high dose treatment and validated with quantitative real-time PCR. Two mRNAs SRF and Arrb related to tRF-Glu-CTC-014 changed consistently. GO analysis revealed that the altered target genes of the selected tsncRNAs were most enriched in protein binding and cellular process. Moreover, KEGG pathway analysis demonstrated that altered target genes of tsncRNAs were most enriched in MAPK signaling pathway. ConclusionSalB can promote the expression of tRF-Glu-CTC-014 to treat atherosclerosis.

Yi Mai granule improve energy supply of endothelial cells in atherosclerosis via miRNA-125a-5p regulating mitochondrial autophagy through Pink1-Mfn2-Parkin pathway

Ethnopharmacological relevanceYi Mai granule (YMG) consists of two classic Chinese medicine formulas used to treat cardiovascular disease for centuries. The Pink1-Mfn2-Parkin pathway, a well-recognized mechanism that mediates mitochondrial autophagy, plays a big part in mitochondrial quality control and the maintenance of heart function. However, the effects of YMG on endothelial dysfunction and mitochondrial autophagy remain unknown. Aim of the studyHere, we focused on the therapeutic effects of YMG in improving mitochondrial autophagy and the mechanism of YMG against cardiovascular disease. Materials and methodsIn this study, rats were fed high-fat diet (HFD) for 21 weeks and were given high, medium, and low doses of YMG in stomach. The open field test was used to evaluate the rats’ behavior. Atherosclerotic plaques, blood lipids, and cytokine levels were measured. Mitochondrial autophagy changes were observed by Transmission electron microscope (TEM). Human umbilical vein endothelial cells (HUVECs) were injured by angiotensinⅡ(AngⅡ) and were given high, medium, and low doses of YMG medicated serum in cell culture medium. Pink1-Mfn2-Parkin expression and miRNA 125a-5p expression were measured by RT-PCR and Western blot. ResultsWe demonstrated that the atherosclerosis model group tended to exhibit reduced vitality behaviors. We proved that the atherosclerosis model group showed obvious atherosclerotic plaques, endothelial cells destruction, and high level of blood lipid and cytokines (including hs-CRP, ET). Mitochondria were reduced, and mitophagy was inhibited in aortic cells of the model group. MiRNA-125a-5p was up-regulated; at the same time, Pink1-Mfn2-Parkin-mediated mitochondrial autophagy was prevented. We also proved that AngⅡinjured HUVEC showed obviously low mRNA levels of Pink1, Mfn2, and Parkin. Interestingly, we found that miRNA-125a-5p was significantly down regulated in Ang II-induced HUVECs. In addition, miRNA-125a-5p significantly reduced the protective effect of YiMai Granules against Ang II injury. ConclusionOur finding indicated that Pink1-Mfn2-Parkin-mediated mitochondrial autophagy plays a crucial role in alleviating atherosclerosis. YMG alleviated atherosclerosis by potentially activating mitochondrial autophagy may via miRNA-125a-5p, regulating Pink1-Mfn2-Parkin pathway, and regulating proinflammatory factors, vasoconstriction cytokine, and blood lipids.

Effect of local unstable atherosclerotic plaque on plaque formation in the carotid artery and abdominal aorta of rabbits

To analyze the effect of local unstable atherosclerotic plaque on plaque formation in the carotid and aortic arteries of rabbits. Thirty New Zealand white rabbits were randomly divided into atherosclerosis model group, highfat diet feeding group, and normal chow feeding group (blank control group). In the model group, carotid artery balloon injury was induced after 4 weeks of high-fat diet feeding. Eight weeks later, all the rabbits were euthanized for histopathological examination of the carotid artery and abdominal aorta, and the mean intimal thickness and plaque to lumen area ratio were measured using image analysis software. Venous blood samples were collected from the rabbits for blood lipid analysis. At the ends of 4, 8 and 12 weeks, the rabbits in the model group and high-fat feeding group, but not those in the blank control group, all showed significant weight gain compared with their body weight at 0 week (P < 0.05). The mean intimal thickness was significantly greater in atherosclerosis model group than in the other two groups (P < 0.05). In atherosclerosis model group, the mean intimal thickness and plaque to lumen area ratio in the injured carotid artery were significantly greater than those in the contralateral carotid artery and abdominal aorta (P < 0.05). At the end of the 12 weeks, the levels of triglyceride (TG), total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C) and highsensitivity C-reactive protein (CRP) were all significantly higher in the model group and high-fat feeding group than in the blank control group (P < 0.05); the levels of TG, TC, LDL-C, or HDL-C did not differ significantly between the model group and high-fat feeding group (P>0.05), but the level of CRP was significantly higher in arteriosclerosis model group (P < 0.05). Local unstable atherosclerotic plaque can increase the level of CRP and promote the formation of atherosclerotic plaques in the carotid artery and abdominal aorta in rabbits.

Nrf2 deficiency attenuates atherosclerosis by reducing LOX-1-mediated proliferation and migration of vascular smooth muscle cells

Background and aimsOxidative stress and abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) influence atherosclerosis formation and development. Oxidative stress significantly influences the abnormal proliferation and migration of VSMCs, and nuclear factor erythroid 2-related factor 2 (Nrf2) is a major antioxidant factor. However, the precise function of Nrf2 in the regulation of abnormal proliferation and migration of VSMCs and atherosclerosis is unclear. MethodsWe investigated the proliferation and migration of VSMCs in atherosclerosis in male Apoe−/− and Apoe−/−Nrf2−/− mice fed a high-fat diet for 12 weeks. In cultured mouse VSMCs, we studied the effect of Nrf2 on ox-LDL-stimulated proliferation and migration by using siRNA treatment to silence Nrf2. We then performed dual luciferase reporter and immunoprecipitation assays to study the interaction between Nrf2 and the promoter sequence of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). ResultsOur results demonstrate that Nrf2 expression levels were increased in the aorta and VSMCs of mice in the atherosclerosis model group compared with the control group. We also provide evidence that Nrf2 deficiency attenuated atherosclerotic plaque burden, diminished proliferation, and migration of VSMCs but enhanced VSMC-specific marker gene expression in vitro and in vivo. This is related to Nrf2 binding to the promoter sequence of LOX-1. Furthermore, Nrf2 downregulation contributes to restrain both transcriptional and translational activities of LOX-1. ConclusionsTogether, our data indicate that Nrf2 insufficiency is linked to attenuation of atherosclerosis, and could diminish the pathological process by blunting LOX-1-mediated proliferation and migration of VSMCs.

Effects of Apigenin on the Expression of LOX-1, Bcl-2, and Bax in Hyperlipidemia Rats.

We aimed to investigate the impact of apigenin on LOX-1, Bcl-2, and Bax expression in hyperlipidemia rats and explore the possible molecular pathological mechanism of apigenin in improving hyperlipidemia and preventing atherosclerosis. In hyperlipidemia models, the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and the LOX-1 protein expression were apparently increased (P<0.01), while the high-density lipoprotein cholesterol (HDL-c) levels and the ratio of Bcl-2/Bax were reduced significantly (P<0.01) in comparison with the standard control group. After the treatment of apigenin, the levels of TC, TG, LDL-c, and the LOX-1 protein expression were noticeably decreased (P<0.01), while the levels of HDL-c and the Bcl-2/Bax ratio were increased (P<0.01). The intima was thickened and had protrusions in the hyperlipidemia model group compared to the normal control group. In comparison with the atherosclerosis model group, the degree of aortic lesions in the low-dose, middle-dose, high-dose groups was alleviated. Apigenin can reduce the level of blood lipid, improve hyperlipidemia, and prevent atherosclerosis in hyperlipidemia rats. The molecular mechanism may be related to inhibiting LOX-1 gene expression and increasing the Bcl-2/Bax ratio.

Network analysis of the effects of long non-coding RNAs in artemisinin treatment of atherosclerosis in APOE-/- mice.

Atherosclerosis has become a worldwide medical burden. Our previous studies have shown that artemisinin (ART) had the capability to reduce atherosclerosis. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are involved in the development of atherosclerosis. However, whether lncRNAs might participate in the mechanism through which artemisinin mitigates atherosclerosis has not been reported. Eight-week-old apolipoprotein E deficient (APOE-/-) mice were divided into two groups, one of which was treated with artemisinin. Red oil O staining was used to measure the sizes of the atherosclerotic lesions. We conducted deep sequencing to investigate lncRNA profiles in the aorta tissue in high-fat diet fed APOE knockdown mice with and without artemisinin treatment. CeRNA network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed through bioinformatics analysis. RT-PCR was used to validate the differentially expressed lncRNAs. A total of 102 lncRNAs and 4,630 mRNAs were differentially expressed (p < 0.05) between the artemisinin treatment group and atherosclerosis model group. KEGG and GO analyses indicated that the categories metabolic process, specific amino acid degradation and PI3K-Akt signaling pathway are involved in the effects of artemisinin treatment in atherosclerosis (q < 0.05). LncRNA ENSMUST00000099676.4, ENSMUST00000143673.1, ENSMUST00000070085.5 and ENSMUST00000224554 might be engaged in the treatment mechanism through which artemisinin alleviates atherosclerosis. These findings indicated the possible mechanism and therapeutic role of lncRNAs in artemisinin treatment of atherosclerosis and provided a theoretical basis for the future application of artemisinin in patients with atherosclerosis.

Study on Damage Mechanism and Repair of Vascular Endothelial Cells Based on Ultrasound Technology.

Objective To detect the endothelial function of external iliac artery in rats with different stages of atherosclerosis by high-resolution ultrasound, so as to provide experimental methodological basis for evaluating the function of vascular endothelial cells by ultrasound. Methods The animals were randomly divided into the control group (n = 6) and the atherosclerosis model group (n = 15). The atherosclerosis group was further divided into 4-week group, 8-week group, and 12-week group, with 5 animals in each group. After separating and grinding rat spleen, the obtained cells were cultured by density gradient centrifugation. After the cells adhered, the morphology of the cells was observed under a microscope and identified by DiI-Ac-LDL and FITC-UEA-I double staining. The activities of LDH and SOD, the contents of MDA and GSH, and the contents of NO in plasma were detected by biochemical methods. Results The protective effect of rosanilin on brain injury in rats with acute hypobaric hypoxia and its regulation on the expression of pAkt protein; ox-LDL inhibited the proliferation activity of EPCs in a concentration-dependent manner. The expression of KLF2 and S1PR1 in HAEC can be knocked down by small interfering RNA, and knocking down KLF2 can not only downregulate the expression of S1PR1 but also downregulate HAVEN. With the development of atherosclerosis, the endothelium-dependent relaxation function and endothelium-independent relaxation function of the control group and the atherosclerosis model at 4, 8, and 12 weeks were damaged in different degrees and gradually aggravated. Conclusion Atherosclerosis is a disease with both morphological and functional damage, and vascular endothelial function is damaged in the early stage with corresponding pathological changes. Ultrasound is an effective method to evaluate vascular endothelial function.

Chaihu-Shugan-San and absorbed meranzin hydrate induce anti-atherosclerosis and behavioral improvements in high-fat diet ApoE-/- mice via anti-inflammatory and BDNF-TrkB pathway

The comorbidity of coronary heart disease (CHD) and depression in patients is extremely prevalent, with a rate from 20 to 50%, while depression-like behaviors exist in a larger percentage of patients. Therefore, the study of comorbidities is particularly urgent. Chaihu-Shugan-San (CSS), a classical traditional Chinese medicine formula, has been used to treat CHD with depression for hundreds of years. However, the mechanism of its action on comorbidities remains unclear. Here, we focused on the behavioral changes in ApoE−/− mice fed a high-fat diet (HFD) and elucidated the mechanism of CSS and its main absorbed component, meranzin hydrate (MH), as an anti-atherosclerosis and anti-depression agent. In the present study, mice were fed an HFD for 16 weeks and were intragastrically administered high and low doses of CSS and MH. Depressive-like behaviors were evaluated by the sucrose preference test, the open-field test, the light-dark test and the tail-suspension test, after which atherosclerotic plaques, plasma lipids, inflammatory cytokine levels and the expression of BDNF/TrkB were measured. We demonstrated that the atherosclerosis model group exhibited significant depressant behaviors. Moreover, CSS inhibited depressive-like behavioral changes, reduced atherosclerotic plaque areas, plasma total cholesterol, triglycerides, LDL-cholesterol levels and inflammatory cytokines including TNF-α, IL-1β, and IL-6 in plasma and hippocampi, increased the protein and mRNA expression of BDNF and TrkB in the aorta and the hippocampus. Interestingly, MH, the main component in CSS that is absorbed in the plasma and hippocampus, exerted effects similar to those of CSS. In addition, MH increased the protein and mRNA expression of BDNF and TrkB in human umbilical vein endothelial cells (HUVECs) induced by LPS. Collectively, these results suggest that MH represents the CSS decoction, induces anti-atherosclerosis effects and improves depression-like behaviors in HFD-fed ApoE−/− mice. Moreover, the regulation of proinflammatory factors and BDNF-TrkB signaling are possibly involved in this process. Our findings indicate that MH is a potential phytochemical compound for the prevention of the comorbidity of atherosclerosis and depression.

Effects of Xuezhikang (Red Yeast Rice) on Blood lipids, Hemorheology and the Expression of P65 and Tissue Factor in Atherosclerotic Rats

Objective: To observe the effects of Xuezhikang (red yeast rice) on blood lipids, blood rheology, and expression of P65 and tissue factor, and to explore the anti-atherosclerosis effect and related mechanisms of Xuezhikang (red yeast rice). Methods: 32 Wistar rats were randomly divided into normal control group, Xuezhikang treatment group, lovastatin treatment group and atherosclerosis model group (8 in each group). blood lipids, blood rheology, malondialdehyde (MDA), total antioxidant capacity (t-AOc), and expression of aortic tissue factor (tF) and P65 were measured in each group. results: (1) Both Xuezhikang and lovastatin could reduce blood lipid levels, but there was no significant difference between the two groups; (2) Both Xuezhikang and lovastatin can improve the hemorheology of atherosclerotic rats, but the difference between the two groups is not signifcant; (3) Compared with lovastatin, Xuezhikang inhibited the expression of TF and P65 in aorta of rats with atherosclerosis; (4) Compared with lovastatin, the Xuezhikang group had lower MDA levels and higher T-AOC. Conclusion: Xuezhikang can improve blood lipid levels and hemorheology in rats with atherosclerosis. Compared with lovastatin, Xuezhikang has stronger effects on inhibiting oxidative stress and down-regulating the expression of tissue factor and P65.

Effects of simvastatin on aortic vascular endothelial cell apoptosis and Bcl-2 protein expression in a rat model of atherosclerosis

To explore the effects of simvastatin on vascular endothelial cell apoptosis and Bcl-2 protein expression in the aorta in a rat model of atherosclerosis. Thirty-six rats were randomized into control group (n=10), atherosclerosis model group (n=13) and simvastatin intervention group (n=13). In the latter two groups, rat models of atherosclerosis were established by intraperitoneal injection of vitamin D3 combined with high-fat feeding for 6 weeks, and the control rats were fed with regular diet. In the intervention group, the rats were further fed with high-fat diet with daily simvastatin treatment for 4 weeks. After the treatments, the pathological changes and plaque in the thoracic aorta were observed, and the expression of Bcl-2 protein was detected with immunohistochemistry. TUNEL assay was used to determine the apoptosis index (AI) of the vascular endothelial cells. Compared with that in the control group, Bcl-2 protein expression in the aorta of atherosclerotic rats was significantly decreased (P<0.05); simvastatin treatment obviously increased the expression of Bcl-2 protein in atherosclerotic rats (P<0.05) to a level similar to that in the control group. The AI was the highest in the model group (P<0.05) and comparable between the control and simvastatin treatment group. The therapeutic effect of simvastatin against atherosclerosis is probably mediated by up-regulation of Bcl-2 protein, which inhibits vascular endothelial cell apoptosis in rats with aortic atherosclerosis.

Impact of olmesartan medoxomil on atherosclerosis lesions in apolipoprotein E knockout mice

To investigate the effect and possible mechanisms of olmesartan medoxomil on atherosclerosis of apolipoprotein E knockout (ApoE(-/-)) mice. Sixteen 6-week-old male ApoE(-/-) mice were randomly divided into atherosclerosis model group fed with high fat diet, and olmesartan medoxomil intervention group fed with high fat diet and olmesartan medoxomil (10 mg·kg(-1)·day(-1,) per gavage). Eight C57BL/6 mice were fed with normal diet, and treated for 12 weeks.The blood pressure and the serum level of lipid were detected; the aorta were removed, oil red staining for plaque area, Hematoxylin and eosin (HE) staining for plaque morphology, Elastica van Gieson (EVG) staining for elastin, and picrosirius red (PSR) for collagen respectively; and the expression of cathepsin S (Cat S), smooth action protein (ASMA) and macrophage surface molecule-3 (Mac-3) were detected by immunohistochemisty analysis. Serum cholesterol and low density lipoprotein levels were significantly higher in atherosclerosis model group than in control group[(15.08±1.64) vs (2.06±0.15) mmol/L, (15.60±1.05) vs (0.00±0.00) mmol/L] (all P<0.01), while triglyceride level was similar between the two group.In contrast to model group, the mice in intervention group showed no statistical difference in blood pressure and plasma lipid levels, while the plaque areas in the aorta were significantly decreased (P<0.05) as well as the expression of Cat S and Mac-3[(2.4±1.2) vs (8.8±3.2)%, (2.2±1.2) vs (7.2±2.8)%] (all P<0.01). In addition, the elastin levels, collagen contents, and the expression of ASMA remained significantly higher compared with model group (P<0.05). Olmesartan medoxomil could slow down the atherosclerosis process, the possible mechanism was implicated with the suppression of Cat S and decreased inflammatory responses alongside the increased elastin and collagen contents.

Effects and mechanisms of ghrelin on plaque neovascularization in rabbits with atherosclerosis

Objective The aim of our study was to investigate the effects and mechanisms of ghrelin on neovascularization in atherosclerosis plaque. Methods 30 male New Zealand rabbits were randomly divided into normal control group(CON group), atherosclerosis model group(AS group), and ghrelin treatment group(ghrelin group), and each group of 10 rabbits. The AS group and ghrelin group underwent balloon-induced arterial wall injury and then fed with high fat diet, the CON group was fed only on a regular diet. They were all fed for 3 months. Then the ghrelin group was given ghrelin 25 μg·kg-1·d-1, the other two groups received the same amount of sterile normal saline only. Four weeks later, body weight and blood lipids were detected. The thickness ratio of the intima to media was measured by HE staining. Degree of intra-plaque angiogenesis was evaluated by CD31+ cells immunohisto-chemistry. The vascular endothelial growth factor(VEGF) and vascular endothelial growth factor receptor 2(VEGFR2) were detected by quantitative realtime PCR and Western blot. The expressions of matrix metalloproteinase(MMP)-2 and MMP-9 were detected by immunohistochemistry and Western blot. Results (1)No significant differences in body weight and blood lipids were found between the AS group and the ghrelin group(P>0.05), but both items were significantly higher than those of the CON group(P<0.05). (2)The thickness ratio of the intima to media in the ghrelin treated group was distinctly less than that in the AS group(P<0.05). (3)Compared with the AS group, the ghrelin group showed significantly decreased microvascular density and the expressions of VEGF and VEGFR2(P<0.05). (4)Compared with the AS group, ghrelin dramatically inhibited the plaque contents of MMP-2 and MMP-9(P<0.05). Conclusions Ghrelin is able to inhibit the growth of neovascularizationin in the atherosclerotic plaque and the development of plaque. And these beneficial effects derive from downregulation of VEGF, VEGFR2, MMP-2, and MMP-9 at the advanced stage of atherosclerosis in rabbits. (Chin J Endocrinol Metab, 2015, 31: 717-724) Key words: Ghrelin; Neovascularization; Atherosclerosis; Plaque stability

Comparison of the effects of escitalopram and atorvastatin on diet-induced atherosclerosis in rats

Atherosclerosis is one of the most common disorders among the elderly. Depression may be associated with the development of atherosclerosis. Thus, the aim of this study is to evaluate and compare the effects of escitalopram (a selective serotonin reuptake inhibitor) with atorvastatin (a well known antihyperlipidemic drug) on high fat diet induced atherosclerosis in rats. The results of this study showed that the administration of either escitalopram or atorvastatin for 6 weeks was associated with a significant decrease in serum levels of total cholesterol, triglycerides, low density lipoproteins, very low density lipoproteins, and serum malondialdehyde, and a significant increase in high density lipoproteins when compared with the atherosclerosis model group. Histopathological examination of the aortas from the test rats revealed significant regression of atherosclerotic changes, together with a significant decrease in vascular cell adhesion molecule-1 (VCAM-1) expression in the media of both the escitalopram group and the atorvastatin group when compared with the atherosclerosis model group. This study has shown that escitalopram reduced atherosclerotic changes, thus its use as an antidepressant in elderly patients should be considered.

Rosuvastatin attenuates atherosclerosis in rats via activation of scavenger receptor class B type I

In order to investigate the effect and mechanism of action of rosuvastatin on atherosclerotic lesion in a Wistar rat model, 16 Wistar rats were fed a cholesterol-rich, vitamin D3 overload diet and underwent balloon injury of the aorta. One day prior to injury, half of the rats began rosuvastatin treatment (5mg/kg/d) via oral gavage. Eight control rats received a basal diet and sham operation. After 14 weeks of treatment, the animals were sacrificed. Blood was collected to measure lipid and angiotensin II (Ang II) levels and morphologic analysis was performed on the aorta. Scavenger receptor-class B type I (SR-BI), Ang II type-1 (AT1) receptor and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK1/2) protein and mRNA levels were measured via Western blot and real time reverse transcriptase polymerase chain reaction, respectively. Spearman's rank correlation was utilized to examine the relationships between SR-BI and Ang II or AT1 receptor expression. The atherosclerosis model group demonstrated an increase in plasma lipid levels and aortic plaque formation. After 14 weeks of treatment with rosuvastatin, there was a significant decrease in plasma lipid and Ang II levels accompanied by an improvement in aortic lesions. Rosuvastatin increased the expression of SR-BI but significantly inhibited the expression of AT1 receptor and p-ERK1/2. SR-BI protein expression was inversely correlated with both the level of Ang II and expression of the AT1 receptor. In conclusion, rosuvastatin attenuates atherosclerosis in the Wistar rat model, and its anti-atherosclerotic activity may be through upregulation of SR-BI expression and inhibition of p-ERK1/2 levels and AT1 receptor expression.

Effect of 7-Difluoromethyl-5, 4΄-dimethoxygenistein on aorta atherosclerosis in hyperlipidemia ApoE-/- mice induced by a cholesterol-rich diet

Purpose7-Difluoromethyl–5, 4′-dimethoxygenistein (DFMG), prepared by the difluoromethylation and alkylation of Genistein, is an active new chemical entity. Its anti-atherosclerosis effect was found in a series of studies in vitro. In this article, we explored and evaluated the anti-atherosclerosis effect via its protection of endothelial function in ApoE−/− mice that were fed a high-fat diet.MethodsFive C57BL/6J mice were selected as a control group and were fed a 1% high-fat diet (control group, n = 5). Five ApoE−/− mice that were fed a high-fat diet for 16 weeks were selected as the atherosclerosis model group (model group, n = 5). In the phase I study, 25 ApoE−/− mice were provided a prophylactic treatment with different drugs at the beginning of the 16 week high-fat diet: 5 mg/gk genistein (genistein 1 group, n = 5), 5 mg/kg lovastatin (lovastatin1 group, n = 5), 2.5 mg/kg DFMG (DFMG L1 group, n = 5), 5 mg/kg DFMG (DFMG M1 group, n = 5), and 10 mg/kg DFMG (DFMG H1 group, n = 5). In the phase II study, 25 atherosclerosis model, ApoE−/− mice were treated with different drugs and fed a high-fat diet for 16 weeks: 5 mg/gk genistein (genistein 2 group, n = 5), 5 mg/kg lovastatin (lovastatin 2 group, n = 5), 2.5 mg/kg DFMG (DFMG L2 group, n = 5), 5 mg/kg DFMG (DFMG M2 group, n = 5), and 10 mg/kg DFMG (DFMG H2 group, n = 5). The plasma levels of lipids, von Willebrand factor (vWF), and nitrite were compared between phases I and II. Endothelium-dependent relaxation (EDR), aortic lesion development, and quantification in thoracic aortas were measured during these two phase studies.ResultsCompared to the model group, the lipid and vWF plasma levels were significantly lower, the plasma nitrite levels were significantly higher, the fatty streaks of aortic lesions were significantly lower, and the endothelium dependent relaxation was significantly higher after both phase studies (P < 0.05). The DFMG supplementation led to significant plasma nitrite increment in all groups after both phase studies (P < 0.05). There were significantly decreased fatty streaks of aortic lesions in DFMG-prevented and DFMG-treated mice (P < 0.05). There was a significant increase in EDR in all prophylactic treatment groups and treatment groups (P < 0.05). We further demonstrated that the preventative effect was more obvious than the therapeutic effect.ConclusionOur results suggest that DFMG could work in prophylactic and therapeutic treatments for atherosclerosis development.

Observation on cerebrovascular hemodynamic index in experimental atherosclerotic rabbits

目的 观察动物模型动脉粥样硬化(atherosclerosis,AS)发生、发展过程中脑血管血液动力学指标(cerebrovascular hemodynamic indes,CVHI)的变化规律.方法 新西兰大耳白兔20只,随机分为两组:12只为动脉粥样硬化模型组,给予高脂饲料喂养;8只为对照组,给予普通基础饲料喂养.于12周末检测所有兔CVHI,同期进行病理检查,并观察离体血管的顺应性.结果 与对照组比较,AS模型组兔的最大血流速度和最小血流速度均有明显降低;而外周阻力、特性阻抗和脉搏波波速明显升高;血管顺应性明显降低.病理结果显示,AS模型组兔的颈动脉粥样硬化斑块形成明显,管腔狭窄.结论 CVHI能正确反映颈动脉病变和脑血管病理生理变化,对早期脑动脉粥样硬化的诊断具有重要的意义。