Atherosclerosis is a cardiovascular disease, which is characterized by the interaction between carbohydrates, lipids, cells and various other molecules and genetic factors. Previous studies have demonstrated that resveratrol (RV) served protective roles in numerous types of human disease by regulating different signaling pathways. The aim of the present study was to investigate the therapeutic effects of RV and analyze the potential RV-mediated mechanism in umbilical vein endothelial cells (UVECS) in atherosclerosis model mice. Reverse transcription-quantitative PCR, western blotting and immunohistochemistry were used to analyze the therapeutic effects of RV both in vitro and in vivo. The results demonstrated that total cholesterol, triglycerides, low-density lipoprotein cholesterin and high-density lipoprotein cholesterin levels were significantly decreased in the RV group compared with the control group. RV demonstrated significant anti-atherosclerotic activity, which was determined through the atherogenic index, 3-hydroxy-3-methyl-glutaryl-Coa (HMG-CoA) reductase activity and marker enzymes, such as lactate dehydrogenase, creatine phosphokinase, aspartate transaminase, alanine transaminase and alkaline phosphatase. It was also observed that RV treatment significantly decreased the area of the arteriosclerotic lesion in the RV group compared with the control, as well as significantly decreasing the expression levels of matrix metalloproteinase-9 and CD40 ligand (CD40L) in arterial lesion tissue compared with the control group. Serum expression levels of tumor necrosis factor-α and C-reactive protein were also significantly decreased by RV treatment compared with the control group. Furthermore, RV treatment significantly decreased the expression levels of PI3K, AKT and mTOR in UVECS in vitro. In conclusion, these results suggested that the anti-atherosclerotic activity of RV may be due to its modulatory activity over the PI3K/AKT/mTOR signaling pathway. These findings suggested a potential novel treatment option for patients with atherosclerosis.

This study investigated the expression of programmed cell death protein 4 (PDCD4) in rat models of coronary atherosclerosis (AS) and analyzed its role and mechanism. A total of 80 Wistar rats were selected and divided into the control group (n=40) and research group (n=40) according to the principle of similar body weight, of which coronary AS models were established in rats in the research group. PDCD4 expression in coronary artery tissues was detected using western blotting, and the expression of interleukin-6 (IL-6) and IL-8 in the coronary artery tissues were measured by means of reverse transcription-polymerase chain reaction (RT-PCR). The apoptotic rate of coronary artery smooth muscle cells was determined via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The relative expression of PDCD4 in coronary artery tissues in the research group was obviously higher than that in the control group, and the difference was statistically significant (t=6.121, P<0.01). In terms of the relative expression of messenger ribonucleic acid (mRNA) of IL-6 in the coronary artery tissues, the research group had a remarkably higher level than the control group, with a statistically significant difference (t=21.03, P<0.01). The difference in the relative expression of IL-8 mRNA between the research group and the control group was statistically significant, of which a much higher level was detected in the research group (t=19.96, P<0.01). The apoptotic rate of smooth muscle cells in the research group was increased notably compared with that in the control group, and the difference was statistically significant (t=5.985, P<0.01). PDCD4 may participate in the formation of coronary AS plaque, and its possible function in the process is to inhibit the proliferation of vascular smooth muscle cells and promote the upregulation of IL-6 and IL-8.

As a global health problem, cardiovascular disease threatens the lives of human beings. It has been reported that microRNAs (miRs) are important in regulating coronary atherosclerosis. In the present study, the expression levels of miR-370 in peripheral blood mononuclear cells of patients with coronary atherosclerosis were significantly increased compared with healthy patients, as demonstrated by reverse transcription-quantitative polymerase chain reaction analysis. Additionally, the target of miR-370 was predicted as Forkhead Box 1 (FOXO1) with bioinformatics, and was confirmed by a dual luciferase assay. The mRNA and protein expression levels of FOXO1 were inhibited by miR-370. Furthermore, the invasion and proliferation of human umbilical vein endothelial cells were promoted by miR-370 via inhibiting the expression of FOXO1. The results obtained in the present study demonstrated that miR-370 served an important role in regulating coronary atherosclerosis via targeting FOXO1. The present data also indicated that miR-370 may be a promising molecular target for treating coronary atherosclerosis.

The aim of this study was to explore the use of urantide as an antagonist of the urotensin II (UII) receptor, G protein-coupled receptor 14 (GPR14), to protect against atherosclerosis (AS) in rats. The AS rat model was induced by an intraperitoneal injection of vitamin D3 (VD3) into rats fed with a high-fat diet for four weeks. Urantide was then injected into the rats. Immunohistochemical staining, serum biochemical assay, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to investigate the expression of UII and its receptor GPR14 in the AS rat model. Four weeks after induction, pathological changes typical of AS were observed in the AS rat model. In the plaques of the aortic tunica intima and tunica media, expression of UII and GPR14 was observed. The protein and gene expression levels of UII and GPR14 in the model group were significantly increased compared with those in the normal group (P<0.01). Urantide ameliorated the pathological changes of AS in the rat model and reduced the gene and protein expression levels of UII and GPR14 (P<0.05 or P<0.01). UII is associated with AS and the UII receptor GPR14-specific antagonist, urantide, demonstrates the ability to protect against AS. Thus, this study provides new insight and experimental theories for the clinical application of urantide to treat AS.

The effect of rosuvastatin on the expression of candidate gene polypeptide N-acetylgalactosaminyltrans ferase 3 (GALNT3) in atherosclerosis was studied. Sixty Wistar rats were randomly divided into the control (n=20), model (atherosclerosis group, n=20) and administration (rosuvastatin group, n=20) groups. The atherosclerosis model was established via injecting D3.6 million units of vitamin per kilogram of body weight and then the rats were fed with high-fat diet for 6 weeks. The total cholesterol, serum triglyceride and nitric oxide contents were detected using the kits, the morphological changes in thoracic aorta were observed via hematoxylin and eosin (H&E) staining, the mRNA expression of candidate gene GALNT3 was detected via reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression of candidate gene GALNT3 was detected via western blot analysis. Compared with those in the control group, the contents of serum triglyceride and total cholesterol in the model group were significantly increased, and then significantly decreased after drug administration. Morphological observation showed that the surface of thoracic aorta was not smooth with endothelial shedding, and the smooth muscle cells were arranged irregularly and their number was obviously increased. Moreover, RT-PCR and western blot analysis revealed that the mRNA and protein expressions of GALNT3 were significantly increased in the administration group. Rosuvastatin can therefore significantly upregulate the expression of candidate gene GALNT3 in atherosclerosis, thereby reducing the incidence of atherosclerosis.

The purpose of the current study was to investigate the mechanism by which fisetin improves atherosclerosis (AS) by regulating lipid metabolism and senescence in apolipoprotein E-deficient (apoE-/-) mice. An AS model was established by feeding apoE-/- mice a high-fat diet. Mice were randomly divided into the model group (n=18), the fisetin group (n=18) and the atorvastatin group (n=18). The control group (n=18) was composed of wild-type C57BL/6 mice of the same age and genetic background. The fisetin and atorvastatin groups were respectively treated with aqueous solutions of fisetin (12.5 mg/kg) and atorvastatin (2 mg/kg) via oral gavage daily for 12 weeks. The pathological morphology, lipid accumulation, collagen deposition of the aortic sinus were observed, serum lipids, superoxide dismutase (SOD) and malondialdehyde (MDA) levels and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured in the peripheral blood serum. Additionally, the expressions of proprotein convertase subtilisin/kexin type 9 (PCSK9), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), tumor suppressor protein p53 (p53), cyclin-dependent kinase inhibitor 1A (p21) and multiple tumor suppressor-1 (p16) were analyzed in the aorta. The results of the current study indicated that compared with the control group, a large area of AS plaque in the aortic sinus that contained a large amount of red-stained lipids and decreased collagen fiber content were found in the model group, which exhibited higher total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), oxidized low-density lipoprotein (ox-LDL) and MDA levels; higher ALT and AST activities, lower high-density lipoprotein cholesterol (HDL-C) and SOD levels and increased expression levels of PCSK9, LOX-1, p53, p21 and p16. Fisetin is a phytochemical and bioflavonoid that serves a potential role in chronic diseases including AS, obesity, diabetes and cancer due to its wide biological activities, such as regulating lipid metabolism and anti-aging, anti-oxidation and anti-inflammatory. Atorvastatin is recognized as a first-line treatment drug for AS; therefore it was used as a positive control in the current study. Following fisetin and atorvastatin treatment, both the AS plaque and the lipid accumulation in the aortic sinus were significantly reduced, and the expressions of PCSK9, LOX-1 and aging markers, including p53, p21 and p16 were downregulated.

Metabolites are the final products of cellular regulation processes, their level is the ultimate response of biological systems to environmental and genetic changes. Therefore, the identification of key metabolites is required for the diagnosis and therapy of diseases. In this study, atherosclerosis-related gene expression profile information was extracted from ArrayExpress database (GEOD-57691), and analyzed with limma package. Furthermore, we constructed an intricate multi-omics network involved in genes, phenotypes, metabolites and their associations. To identify the prioritization of atherosclerosis-related metabolites, the relation score of each metabolite in the composite network was computed with the random walk with restart (RWR) method. The top 50 metabolites and top 100 genes were chosen based on the score in the weighted composite network. Consequently, several key metabolites that were ranked in the top 5 of relation score or degree greater than 70 were confirmed. Particularly, metabolites Tretinoin and Estraderm not only have high relation scores, but also contain more degrees. Moreover, we obtained 24 co-expression genes that may be regarded as the targets of atherosclerosis therapy. Therefore, identification of metabolite prioritizations by the composite network integrated the information of genes, phenotypes and metabolites may be available to diagnose atherosclerosis, and can provide the potential therapeutic strategies for atherosclerosis.

Expression and function of Wnt signaling pathway in rats with atherosclerosis (AS) were investegated. The AS model of rats was established after 8-week continuous feeding of a high-fat diet, with normal rats as the control. Blood was taken from the carotid artery to detect the level of blood lipid. Aortic slices were made to observe the pathological changes of the aorta after the rats were sacrificed. Enzyme-linked immunosorbent assay kits were used to detect the contents of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Western blot analysis and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) were performed to detect the expression levels of related proteins and mRNA in rat Wnt signaling pathway. Correlation analysis between the protein expression level of vascular endothelial growth factor (VEGF) and that of Wnt1 was conducted. Aortic slices showed that the ratio of intima thickness to media thickness of the rats in the model group was higher than that of in the control group (P<0.01). Blood lipid and the contents of IL-6 and TNF-α of the rats in the model group were higher than those of the rats in the control group (P<0.01). Semi-quantitative RT-PCR indicated that mRNA expression levels of Wnt1, β-catenin and dickkopf1 in the aorta of rats in the model group were increased compared with those of control group (P<0.01). The results of western blot analysis revealed that the protein expression levels of Wnt1, β-catenin, DKK1 and VEGF of the rats in the model group were remarkably higher than those of the control group (P<0.01). The level of VEGF protein was positively correlated with that of Wnt1 (P<0.05, r=0.7810). The activation of Wnt signaling pathway in the aorta of the rats with AS can induce the expression of relevant inflammatory cytokines. It has the effects of promoting the progression of AS and accelerating angiogenesis.

Atherosclerosis is the leading cause of death from vascular diseases worldwide, and endothelial cell (EC) dysfunction is the key cause of atherosclerosis. miR-155 was found to induce endothelial injury and to trigger atherosclerosis. In addition, brain and muscle ARNT-like protein-1 (Bmal1) has been found to be closely related to EC function. Therefore, the present study aimed to explore the mechanism underlying the regulation of Bmal1 by miR-155 in the induction of EC apoptosis and inflammatory response in atherosclerosis. The atherosclerosis model in apolipoprotein E (ApoE)- / - mice was established. miR-155 and Bmal1 expression was quantified by RT-qPCR and western blot analysis, respectively. The role of miR-155 and Bmal1 in atherosclerosis was evaluated through changes in cardiac function, plaque area, cardiomyocyte apoptosis, and inflammatory factor levels in mice. Moreover, the regulatory relationship between them was identified by dual-luciferase reporter gene assay to explore the mechanism of action of miR-155. After the modeling, the expression of miR-155 was upregulated and Bmal1 was downregulated in aorta, and there was a significant linear correlation between them. Upregulation of miR-155 increased the atherosclerotic plaque area, cell apoptosis, total cholesterol (TC) and triglyceride (TG), as well as weakened aortic diastolic function. However, opposite changes occurred after downregulation of miR-155 or an increase in Bmal1. In addition, the microRNA.org website predicted that there were targeted binding sites between miR-155 and Bmal1, which was verified with a dual-luciferase reporter gene assay. miR-155 was able to inhibit the expression by targeting Bmal1. Moreover, a rescue experiment showed that Bmal1 hindered the promotion of miR-155 in regards to atherosclerosis. In conclusion, miR-155 induces EC apoptosis and inflammatory response, weakens aortic diastolic function, and promotes the progression of atherosclerosis through targeted inhibition of Bmal1.

This study investigated the correlation between the levels of interleukin (IL)-17 and IL-18 and atherosclerotic plaques. A total of 60 Apo E gene (Apo E-/-) mice were fed with high-fat diet in the model group and 20 wild male C57BL/6 mice were fed with the basic diet in the control group. The serum levels of IL-17 and IL-18 were determined by enzyme-linked immunosorbent assay. Carotid artery ultrasonography was performed and divided into stable plaque, unstable plaque and non-plaque groups. The severity of plaque was estimated by semi-quantitative method and divided into grades I, II and III. The expression levels of low-density lipoprotein cholesterol, plasma total cholesterol and blood glucose level in the model group induced by high-fat diet were significantly higher than those in the control group (P<0.05). The level in the model group was significantly higher than in the control group at the 16th week (P<0.05). The expression of IL-17 and IL-18 in the model group was significantly higher than that in the control group (t=6.903, 11.02, P<0.05). The concentration of IL-17 and IL-18 in the non-plaque group was significantly lower than that in the stable plaque and unstable plaque groups (P<0.05). The concentration of IL-17 and IL-18 in the stable plaque group was significantly lower than that in the unstable plaque group (P<0.05). Based on the correlation of IL-17 and IL-18 expressions in the model group, the expression of IL-18 increased with the expression of IL-17, indicating that the expression of IL-17 was positively correlated with that of IL-18 (r=0.7195, P<0.001). In conclusion, serum IL-17 and IL-18 played an important role in the formation and development of atherosclerotic plaque, and were related to the stability and severity of plaque. The expression of IL-17 and IL-18 was positively correlated.

IL-37 is a newly discovered inflammatory factor. However, the protective effect and underlying mechanisms of IL-37 on atherosclerosis remain unclear. In the present study, IL-37 was used for intraperitoneal injection in diabetic ApoE-/- mice caused by streptozotocin. High glucose (HG)/ox-LDL was used to stimulate THP-1 original macrophage followed by IL-37 pretreatment in vitro. The atheromatous plaque area, oxidative stress and inflammation levels in ApoE-/- mice were evaluated, and the level of macrophage ferroptosis was detected in vivo and in vitro. It was identified that IL-37 treatment significantly decreased plaque area in diabetic ApoE-/- mice. IL-37 not only improved blood lipid levels in mice, but also reduced serum levels of inflammatory factors including IL-1β and IL-18. Furthermore, IL-37 increased GPX4 and nuclear factor erythroid 2-related factor 2 (NRF2) in the aorta of diabetic mice. In vitro experiment revealed that IL-37 inhibited HG/ox-LDL-induced ferroptosis in macrophages, as evidenced by improved cell membrane oxidation, reduced malondialdehyde production and increased GPX4 expression. Moreover, it was also found that IL-37 enhanced the nuclear translocation of NRF2 in macrophages, while ML385, a specific NRF2 inhibitor, significantly attenuated the protective effect of IL-37 on macrophage ferroptosis caused by HG/ox-LDL. In conclusion, IL-37 suppressed macrophage ferroptosis to attenuate atherosclerosis progression via activating the NRF2 pathway.

The present study examined the involvement of autophagy as a mechanism in the protective effect of quercetin (QUE) on atherosclerosis (AS) in ApoE-/- mice. An AS model was established by feeding ApoE-/- mice a high-fat diet (HFD). Mice were divided into four experimental groups: The model, QUE, 3-methyladenine (3-MA) and QUE + 3-MA groups. Additionally, age-matched wild-type C57BL/6 mice were used as a Control group. Autophagosomes in the aorta were examined using a transmission electron microscope. Aorta pathology, serum lipid accumulation and collagen deposition were determined by hematoxylin and eosin, Oil Red O and Masson staining, respectively. The levels of cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-18 (IL-18) were measured using ELISA assays. Protein levels of mTOR, microtubule associated protein 1 light chain 3a (LC3), P53 and cyclin dependent kinase inhibitor 1A (P21) in the aorta were analyzed using western blotting. ApoE-/- mice which were fed HFD exhibited substantial AS pathology, no autophagosomes, higher levels of TNF-α, IL-1β, IL-18 and mTOR and lower ratios of LC3 II/I. All these alterations were ameliorated and aggravated by QUE and 3-MA treatment, respectively. The inhibition of AS by QUE may be associated with the enhancement of autophagy and upregulation of P21 and P53 expression.

The role of vascular endothelial cells in acute and chronic vascular inflammatory response has long been recognized. Therefore, persistent vascular inflammation may lead to endothelial dysfunction, thus resulting in the release of pro-inflammatory cytokines and the expression of adhesion molecules, which in turn promote monocyte/macrophage adhesion. Inflammation serves a key role in the development of vascular diseases, such as atherosclerosis. Tyrosol is a natural polyphenolic compound with diverse biological functions, found in large quantities in olive oil or in Rhodiola rosea. The current study aimed to investigate the regulatory in vitro effects of tyrosol on pro-inflammatory phenotypes using Cell Counting Kit-8, cell adhesion assay, wound healing, ELISA, western blotting, duel-luciferase, reverse transcription-quantitative PCR and flow cytometry. The results showed that tyrosol significantly inhibited the adhesion of THP-1 human umbilical vein endothelial cells, reduced lipopolysaccharide-induced cell migration and decreased the release of pro-inflammatory factors and the expression levels of adhesion-related molecules, such as TNF-α, monocyte chemotactic protein-1, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Previous studies indicate that NF-κB could serve a pivotal role in initiating the inflammatory responses of endothelial cells and particularly in regulating the expression of adhesion molecules and inflammatory factors. The results of the current study demonstrated that tyrosol was associated with decreased expression of adhesion molecules and monocyte-endothelial cell adhesion, thus suggesting that tyrosol could be a novel pharmacological approach for treating inflammatory vascular diseases.

Effects of circular antisense non-coding RNA in the INK4 locus (circANRIL) on vascular endothelial injury, oxidative stress and inflammation in rats with coronary atherosclerosis were studied by establishing a rat model of coronary atherosclerosis in which circANRIL was differentially expressed. A total of 40 healthy Sprague Dawley (SD) rats were randomly divided into research group (n=32) and control group (n=8). In research group, a rat model of coronary atherosclerosis was established without special treatment. The blood calcium (Ca2+) and lipid levels in the two groups were compared. After cell transfection, the rats were divided into blank group (untransfected), negative group (transfected with blank vector), circANRIL group (transfected with circANRIL overexpression plasmid) and circANRIL inhibitor group (transfected with circANRIL silencer). Then the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in each group were compared. Western blotting was adopted to detect the expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK), p38MAPK and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Finally, p-p38MAPK/GAPDH, p38MAPK/GAPDH and p-p38MAPK/p38MAPK were calculated. There were significant differences in the levels of serum Ca2+ and lipid between control group and research group (P<0.05). Besides, differences in LDH, SOD, MDA, TNF-α and IL-6 in the supernatant in each group were statistically significant (P<0.05 or P<0.01). Moreover, there were statistically significant differences in the gray values of p-p38MAPK/GAPDH and p38MAPK/GAPDH and their ratio p-p38MAPK/p38MAPK in each group (P<0.05 or P<0.01). Inhibiting the expression of circANRIL in coronary heart disease cases can reduce vascular endothelial injury, oxidative stress and inflammation.

Atherosclerosis is a cardiovascular disease that is pathologically associated with the growth of atherosclerotic plaques and vascular vulnerability. Intravascular ultrasound (IVUS) has been used to evaluate and treat cardiovascular diseases. Accumulating evidence has demonstrated that Gd2O3-doped nanoparticles contrast can be applied for the diagnosis of human diseases. In the present study, eplerenone (EPL), a mineralocorticoid receptor antagonist, was first doped with Gd2O3 nanoparticles (Gd2O3-EPL), following which its diagnostic efficacy for use in IVUS measurements (Gd2O3-EPL-IVUS) was evaluated for patients suspected with atherosclerosis. Gd2O3-EPL-IVUS presented with higher accuracy and sensitivity compared with IVUS in diagnosing 188 patients with suspected atherosclerosis. Gd2O3-EPL-IVUS exhibited stronger signals associated with plaque morphology compared with aloe IVUS for patients with atherosclerosis. In addition, Gd2O3-EPL-IVUS application resulted in clearer arterial plaque images compared with IVUS by binding mineralocorticoid receptors. Atherosclerosis was subsequently confirmed in all patients using computerized tomography-coronary angiography. Gd2O3-EPL-IVUS showed more accuracy in measuring vessel size, plaque burden and minimal lumen area compared with IVUS analysis alone. In conclusion, these outcomes suggest that Gd2O3-EPL-IVUS is a reliable tool for the evaluation of coronary lesions in patients with atherosclerosis.

Sicyos angulatus (SA), a summer annual vine originating from Northeastern USA, is a widely distributed noxious invasive plant. However, the clinical application of SA has not been investigated previously. The purpose of present study was to determine the effects of SA on atherosclerosis and its underlying mechanism. Atherosclerosis was induced by feeding apolipoprotein E-deficient (apoE-/-) mice with an atherogenic diet for 8 weeks. SA was administered daily by oral gavage during induction of atherosclerosis. ApoE-/- mice treated with SA demonstrated a significant reduction in atherosclerotic plaque area in the whole aorta and aortic sinus compared with vehicle-treated mice. The plasma lipid profiles, including triglyceride, total cholesterol, high-density lipoprotein and low-density lipoprotein, were not affected by SA administration. Of note, gene expression levels of proatherogenic cytokines including tumor necrosis factor α (Tnfα) and interleukin-6 (Il-6) were significantly decreased in the aorta of SA administered apoE-/- mice. In lipopolysaccharide-stimulated RAW 264.7 macrophage cells, SA also inhibited the induction Tnfa, Il-6 and Il-1β in a dose-dependent manner. Furthermore, gene expression levels of endothelial cell adhesion molecules, including vascular cell adhesion protein 1 and intercellular adhesion molecule 1 were reduced in the aorta of apoE-/- mice treated with SA, which was followed by diminished aortic infiltration of monocytes/macrophages. In conclusion, to the best of our knowledge, this is the first study to demonstrate that SA is able to suppress the development of atherosclerosis by inhibiting the aortic expression of proinflammatory factors in atherogenic diet-fed apoE-/- mice. The present study may provide novel insights into the application of the environmentally problematic weed SA as a therapeutically effective natural product for preventing atherosclerosis.

Late-stage carotid atherosclerosis has a high incidence rate and may lead to various cerebrovascular diseases. The gene expression profile GSE100927 was selected to identify differentially expressed genes (DEGs) in carotid atherosclerosis. Subsequently, protein-protein interaction, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted. Furthermore, experimental verification was performed using human umbilical vein endothelial cells (HUVECs), human aortic vascular smooth muscle cells (HAVSMCs) and Tohoku Hospital Pediatrics-1 (THP-1)-induced macrophages. The groups were as follows: Control group, solvent control group and palmitic acid group. The levels of reactive oxygen species (ROS) in the three cell types were detected by flow cytometry or fluorescence microscopy. Furthermore, apoptosis of HUVECs and HAVSMCs was assessed by flow cytometry and the nuclear Hoechst 33258 staining of THP-1-induced macrophages was performed. Male late-stage carotid atherosclerosis samples, including 10 control samples and 21 atherosclerosis samples, were selected. Pathway enrichment analysis demonstrated that 'Toll-like receptor signaling pathway' was the top pathway associated with the DEGs. MMP7, MMP9, IL1β, C-C motif chemokine ligand 4 (CCL4), secreted phosphoprotein 1 (SPP1), CCL3 and interferon regulatory factor 5 (IRF5) were selected for experimental verification. Palmitic acid increased the ROS levels and the apoptosis rates of HUVECs and HAVSMCs. However, it did not increase the levels of ROS and did not shrink the nuclei of THP-1-induced macrophages. Furthermore, palmitic acid increased the mRNA levels of IL1β, CCL4, SPP1, CCL3, IRF5, MMP7 and MMP9 in HUVECs and THP-1-induced macrophages, and increased the mRNA levels of CCL4 and MMP9 in HAVSMCs. In conclusion, IL1β, CCL3, CCL4, SPP1, IRF5, MMP7 and MMP9 are important markers of late-stage carotid atherosclerosis.

Ultrasonography in the evaluation and diagnosis of carotid arteries and left ventricular function in patients with subclinical atherosclerosis (SA) was explored. In total, 152 patients with no obvious clinical symptoms of atherosclerosis confirmed by carotid ultrasonography in Tengzhou Central People's Hospital from September 2015 to March 2016 were enrolled as the experimental group, and further 45 patients with normal physical examination at the same time were collected as the control group. Patients in the experimental group were divided into three groups according to Framingham risk assessment: low, middle and high risk. The carotid arteries and left ventricular function of all patients were detected by Doppler ultrasound. There were differences in the systolic pressure, TG and TC between the control group and the experimental group (P<0.05). The expression levels of β, cIMT, Ep and PWVβ increased with the risk degree in the low, middle and high risk groups (P<0.05). The expression levels of LVEDV, LVESV, and LVEF in the experimental group were significantly decreased compared with those in the control group (P<0.05), while the expression levels of LAV, E/e, GLS and GCS were significantly increased compared with those in the control group (P<0.05). There was a difference of left ventricular function parameters in the low, medium and high risk groups (P<0.05). The expression levels of LVEDV, LVESV, LAV and E/e increased with the risk degree in the low, middle and high risk groups (P<0.05). The detection rate of plaque was lower in the low risk group than those in the middle and high risk group (P<0.05). By observing the parameters of carotid arteries and left ventricular function, it was found that ultrasonography has important clinical value in the early diagnosis of SA, and can be promoted in clinic.

Type 2 diabetes mellitus (T2DM) is a prevalent disease worldwide and during its conventional treatment, vascular complications remain unavoidable. Roux-en-Y gastric bypass (GBP) is able to induce the remission of T2DM. However, studies of duodenal-jejunal bypass (DJB), a modified procedure of GBP, are being carried out to investigate its ability to induce the remission of T2DM and protect the aorta from atherosclerosis. The present study aimed to investigate the effect of DJB on the rate of T2DM remission and the prevention of atherosclerosis in the aorta in rats with streptozotocin-induced diabetes without obesity, and to explore the mechanism of DJB in protecting the aorta from atherosclerosis. A T2DM rat model was established with a high-fat diet and low-dose streptozotocin. Surgery was performed to analyze its effects on glucose homeostasis, lipid metabolism, inflammation and pathological changes. Furthermore, changes in c-jun NH2-terminal kinase 1 (JNK1) and inhibitor of κB kinase (IKKβ) genes in the aorta following DJB surgery were examined. Levels of blood glucose, lipids, insulin and tumor necrosis factor (TNF)-α were significantly elevated in the T2DM diabetic model compared with the non-diabetic control. A gradual recovery was observed in the DJB group following surgery. Foam cells and atherosclerotic plaques appeared in the ascending aortic tissue in the sham-surgery and T2DM groups, whereas only slight lesions were observed in the DJB group. The expression levels of JNK1 and IKKβ genes in the aorta were significantly increased in the sham-operated and T2DM groups compared with those in the DJB and normal control groups. The present study demonstrated that DJB caused remission of T2DM without weight loss in non-obese rats. Thus, DJB may delay or prevent the occurrence and development of atherosclerosis in the aorta and this may occur through the JNK1 and nuclear factor κB (NF-κB) signaling pathways.

Previous research has demonstrated that the dual PPARα/γ agonist tesaglitazar reduces atherosclerosis in a mouse model of hyperlipidemia by reducing both lipid content and inflammation in the aorta. However, much of the underlying mechanism of tesaglitazar in non-alcoholic fatty liver disease (NAFLD) remains less clear. The aim of the present study was to determine whether tesaglitazar attenuates NAFLD and atherosclerosis development in diabetic low-density lipoprotein receptor-deficient (LDLr(-/-)) mice. Female LDLr(-/-) mice (3 weeks old) were induced by a high-fat diet (HFD) combined with low-dose streptozotocin (STZ) injection to develop an animal model of type 2 diabetes (T2DM). The mice were randomly divided into two groups: diabetic group (untreated diabetic mice, n=15) and tesaglitazar therapeutic group (n=15, 20 μg/kg/day oral treatment for 6 weeks). Fifteen LDLr(-/-) mice were fed with an HFD as the control group. Tesaglitazar decreased serum glucose and lipid levels compared with the diabetic mice. Tesaglitazar significantly reduced atherosclerotic lesions, lipid accumulation in the liver, macrophage infiltration, and decreased total hepatic cholesterol and triglyceride content compared to the diabetic mice. In addition, tesaglitazar reduced inflammatory markers at both the serum and mRNA levels. Our data suggest that tesaglitazar may be effective in preventing NAFLD and atherosclerosis in a pre-existing diabetic condition by regulating glucose and lipid metabolism, and the inflammatory response.