Danggui Shaoyao powder improves hepatic lipid metabolism in atherosclerosis mice via PPARγ-LXRα-ABCA1 pathway regulation

Objective:To observe the effects of Danggui Shaoyao powder(DSP)on hepatic lipid metabolism and further explore its mechanism of action by peroxisome proliferator-activated receptor(PPARγ)-liver X receptor(LXRα)-adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)pathway regulation.Methods: Eight C57BL/6J male mice were selected as the control group,and 24 ApoE^(−/−)male mice were randomly divided into the atherosclerosis model(AS)group,atorvastatin calcium(AC)group,and DSP group(n=8 each group).To establish an AS model,ApoE^(−/−)mice were fed a high-fat diet for 16 weeks.Pathologic changes in the aortic vasculature and liver were identified using Oil Red O staining.Triglyceride(TG),cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were determined in the livers using a single-reagent GPO-PAP method.Fluorescence quantitative polymerase chain reaction and western blot were used to observe and evaluate the mRNA and protein expression of the PPARγ-LXRα-ABCA1 intermediates in the liver.Results: After 16 weeks of a high-fat diet,ApoE^(−/−)mice showed more Oil Red O staining in the aorta and liver compared to the CONT group.Compared to the AS group,the DSP and AC treatment reduced aortic plaque and hepatic lipid deposition to varying degrees.Furthermore,DSP significantly reduced the hepatic lipid area in ApoE^(−/−)mice(P<.001)and decreased the levels of TG,TC,and LDL-C in liver(P<.001,P=.027,P<.001,respectively).DSP also significantly increased the levels of PPARγ,LXRα,ABCA1,and ABCG1 mRNA expression,as well as the PPARγ,LXRα,ABCA1,and ABCG1 protein expression in liver.Conclusion: DSP improved hepatic lipid metabolism via PPARγ-LXRα-ABCA1 pathway modulation for AS treatment.

Tetramethylpyrazine and paeoniflorin combination(TMP-PF)alleviates atherosclerosis progress by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway

Atherosclerosis remains a great threat to human health worldwide.Previous studies found that tetramethylpyrazine(TMP)and paeonifl orin(PF)combination(TMP-PF)exerts anti-atherosclerotic effects in vitro.However,whether TMP-PF improves atherosclerosis in vivo needs further exploration.The present study aims to assess the anti-atherosclerotic properties of TMP-PF in ApoE^(-/-)mice and explore the related molecule mechanisms.Results showed that TMP and high-dose TMP-PF decreased serum triglyceride and low-density lipoprotein cholesterol levels,suppressed vascular endothelial growth factor receptor 2(VEGFR2)and nuclear receptor subfamily 4 group A member 1(NR4A1)expression in aortic tissues,inhibited plaque angiogenesis,reduced plaque areas,and alleviated atherosclerosis in ApoE^(-/-)mice.Also,TMP-PF exhibited a better modulation effect than TMP or PF alone.However,NR4A1 agonist abolished the anti-atherosclerotic effects of TMP-PF.In conclusion,TMP-PF was first found to alleviate atherosclerosis progression by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway,indicating that TMP-PF had a positive effect on reducing hyperlipemia and attenuating atherosclerosis development.

Targeted delivery of rosuvastatin enhances treatment of hyperhomocysteinemia-induced atherosclerosis using macrophage membrane-coated nanoparticles

Rosuvastatin (RVS) is an excellent drug with anti-inflammatory and lipid-lowering properties in the academic and medical fields. However, this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia (HHcy), including high oral dosage, poor targeting, and long-term toxic side effects. In this study, we applied nanotechnology to construct a biomimetic nano-delivery system, macrophage membrane (Møm)-coated RVS-loaded Prussian blue (PB) nanoparticles (MPR NPs), for improving the bioavailability and targeting capacity of RVS, specifically to the plaque lesions associated with HHcy-induced atherosclerosis. In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4 (TLR4)/hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding and oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathways, reducing pyroptosis and inflammatory response in macrophages. Additionally, MPR NPs reversed the abnormal distribution of adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1)/ATP binding cassette transporter G1 (ABCA1)/ATP binding cassette transporter G1 (ABCG1) caused by HIF-1α, promoting cholesterol efflux and reducing lipid deposition. In vivo studies using apolipoprotein E knockout (ApoE^(−/−)) mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable biosecurity, and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes. These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.

Oligomeric procyanidins combined with Parabacteroides distasonis ameliorate high-fat diet-induced atherosclerosis by regulating lipid metabolism,inflammation reaction and bile acid metabolism in ApoE^(-/-)mice

Atherosclerosis(AS)is the main pathological basis of cardiovascular diseases.Hence,the prevention and treatment strategies of AS have attracted great research attention.As a potential probiotic,Pararabacteroides distasonis has a positive regulatory effect on lipid metabolism and bile acids(BAs)profile.Oligomeric procyanidins have been confirmed to be conducive to the prevention and treatment of AS,whose antiatherosclerotic effect may be associated with the promotion of gut probiotics.However,it remains unclear whether and how oligomeric procyanidins and P.distasonis combined(PPC)treatment can effectively alleviate high-fat diet(HFD)-induced AS.In this study,PPC treatment was found to significantly decrease atherosclerotic lesion,as well as alleviate the lipid metabolism disorder,inflammation and oxidative stress injury in ApoE^(-/-)mice.Surprisingly,targeted metabolomics demonstrated that PPC intervention altered the BA profile in mice by regulating the ratio of secondary BAs to primary BAs,and increased fecal BAs excretion.Further,quantitative polymerase chain reaction(qPCR)analysis showed that PPC intervention facilitated reverse cholesterol transport by upregulating Srb1 expression;In addition,PPC intervention promoted BA synthesis from cholesterol in liver by upregulating Cyp7a1 expression via suppression of the farnesoid X receptor(FXR)pathway,thus exhibiting a significant serum cholesterol-lowering effect.In summary,PPC attenuated HFD-induced AS in ApoE^(-/-)mice,which provides new insights into the design of novel and efficient anti-atherosclerotic strategies to prevent AS based on probiotics and prebiotics.

Hepatocyte growth factor enhances the ability of dental pulp stem cells to ameliorate atherosclerosis in apolipoprotein E-knockout mice

BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.

The Relationship Between NLRP3 Inflammasome and Its Downstream Inflammatory Factors in Obstructive Sleep Apnea Patients with Carotid Atherosclerosis Under Cigarette Exposure

Aim:To study the relationship between NLRP3(nucleotide oligomerization domain[NOD]-,leucine-rich repeats[LRR]-,and pyrin domain-containing protein 3)inflammasome and its downstream inflammatory factors in obstructive sleep apnea(OSA)patients with carotid atherosclerosis(CAS)under cigarette exposure,further exploring the risk factors of CAS in OSA patients.Methods:A total of 109 adult males who underwent polysomnography and carotid artery ultrasonography in our hospital from October 2019 to December 2021 were selected.According to the detection results,they were divided into the OSA group,the CAS group,and the OSA combined CAS group;additionally,29 healthy subjects who underwent a physical examination were also included.According to whether they were smoking,the groups were further divided into smoking and non-smoking groups.The age,body mass index(BMI),blood pressure,apnea-hypopnea index(AHI),lowest blood oxygen saturation(LSaO2),carotid intima-media thickness(CIMT),levels of blood sugar,blood low-density lipoprotein cholesterol(LDLc),and serum NLRP3,interleukin-1β(IL-1β),and interleukin-18(IL-18)of all subjects were recorded.Results:The OSA combined CAS group had higher LDLc levels and AHI and lower LSaO2 than the OSA group and CAS group.The levels of serum NLRP3,IL-1β,and IL-18 in the OSA group were higher than those in the normal control group(P<0.05);and those in the OSA combined CAS group were higher than the OSA group and CAS group(P<0.05),regardless of cigarette exposure.Considering cigarette exposure,serum NLRP3,IL-1β,and IL-18 levels were higher in the OSA,CAS,and OSA combined CAS smoking groups than those in the non-smoking group(P<0.05).Under cigarette exposure,AHI,LDLc,NLRP3,IL-1β,and IL-18 were significantly positively correlated(P<0.05),and LSaO2 was negatively correlated with CAS in OSA(P<0.05).AHI,LSaO2,LDLc,NLRP3,and IL-1βare the risk factors for OSA combined with CAS.Conclusion:LSaO2,AHI,LDLc,NLRP3,and IL-1βare the important risk factors for OSA combined with CAS under cigarette exposure,and their levels can be used to predict the occurrence of CAS in OSA.

Unveiling the oral-gut connection:chronic apical periodontitis accelerates atherosclerosis via gut microbiota dysbiosis and altered metabolites in apoE^(−/−)Mice on a high-fat diet

The aim of this study was to explore the impact of chronic apical periodontitis(CAP)on atherosclerosis in apoE^(−/−)mice fed high-fat diet(HFD).This investigation focused on the gut microbiota,metabolites,and intestinal barrier function to uncover potential links between oral health and cardiovascular disease(CVD).In this study,CAP was shown to exacerbate atherosclerosis in HFD-fed apoE^(−/−)mice,as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining.16S rRNA sequencing revealed significant alterations in the gut microbiota,with harmful bacterial species thriving while beneficial species declining.Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis,leading to elevated levels of taurochenodeoxycholic acid(TCDCA),taurocholic acid(TCA),and tauroursodeoxycholic acid(TDCA).These metabolic shifts may contribute to atherosclerosis development.Furthermore,impaired intestinal barrier function,characterized by reduced mucin expression and disrupted tight junction proteins,was observed.The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions,highlighting the importance of the intestinal barrier in cardiovascular health.In conclusion,this research underscores the intricate interplay among oral health,gut microbiota composition,metabolite profiles,and CVD incidence.These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues,as well as the need for further investigations into the intricate mechanisms linking oral health,gut microbiota,and metabolic pathways in CVD development.

Role of Helicobacter pylori infection in pathogenesis of atherosclerosis

Though a century old hypothesis, infection as a cause for atherosclerosis is still a debatable issue. Epidemiological and clinical studies had shown a possible association but inhomogeneity in the study population and study methods along with potential confounders have yielded conflicting results. Infection triggers a chronic inflammatory state which along with other mechanisms such as dyslipidemia, hyper-homocysteinemia, hypercoagulability, impaired glucose metabolism and endothelial dysfunction, contribute in pathogenesis of atherosclerosis. Studies have shown a positive relations between Cytotoxic associated gene-A positive strains of Helicobacter pylori and vascular diseases such as coronary artery disease and stroke. Infection mediated genetic modulation is a new emerging theory in this regard. Further large scale studies on infection and atherosclerosis focusing on multiple pathogenetic mechanisms may help in refining our knowledge in this aspect.

Retinol binding protein 4 correlates with and is an early predictor of carotid atherosclerosis in type 2 diabetes mellitus patients

The association of retinol binding protein 4 （RBP4） with atherosclerosis of the carotid artery in type 2 diabetes mellitus （T2DM） remains undefined. We aimed to investigate the correlation of RBP4 expression with atherosclerosis of the carotid artery in T2DM. A total of 1,076 subjects were investigated for intima-media thickness of the bilateral common carotid arteries, and they were divided into three groups： in group Ⅰ, patients had normal neck vascular ultra- sound, in group Ⅱ, intimal carotid artery media thickness was equal to or more than 1 mm, and in group Ⅲ, carotid artery plaque was present. Height, weight, blood pressure （BP）, fasting plasma glucose （FPG）, hemoglobin Alc （HbA1c）, total cholesterol （TC）, triglyceride （TG）, low-density lipoprotein cholesterol （LDL-C）, high-density lipopro- tein cholesterol （HDL-C）, apolipoprotein A-1 （apoA-1）, apolipoprotein B （apoB） and lipoprotein （a） [Lp（a）] were determined by routine laboratory methods. RBP4 and high sensitivity C reactive protein （HsCRP） were measured by an enzyme-linked immuno-sorbent assay, and insulin concentration was measured by an electrochemiluminescence sandwich immunoassay. Duration of diabetes, waist and BP, FPG, HbAlc, TG, TC, LDL-C, APOB, Lp（a）, HsCRP, RBP4 and homeostasis model assessment insulin resistance index （HOMA-IR） were significantly lower in group I than in the other two groups （P〈0.01, P〈0.01）. Plasma levels of HbAlc, RBP4, LDL-C, TC, HOMA-IR, HsCRP and Lp（a）, waist and BP were significantly increased in group III than in group II （P〈0.01）. Multivariate logistic regression analysis showed that there were seven factors associated with the occurrence of carotid artery atherosclero- sis and its risks in descending order were： high LDL-C, high waist, high HsCRP, duration of diabetes, high HOMA-IR, HbAlc and high RBP4. Our finding supported that RBP4 was positively correlated with carotid atherosclerosis in patients with T2DM and could be used as an early predictor of cardiovascular disease.

Chronic hepatitis C virus infection and atherosclerosis: Clinical impact and mechanisms

Hepatitis C virus(HCV)infection represents a major health issue worldwide due to its burden of chronic liver disease and extrahepatic manifestations including cardiovascular diseases,which are associated with excess mortality.Analysis of published studies supports the view that HCV infection should be considered a risk factor for the development of carotid atherosclerosis,heart failure and stroke.In contrast,findings from studies addressing coronary artery disease and HCV have yielded conflicting results.Therefore,meta-analytic reviews and prospective studies are warranted.The pathogenic mechanisms connecting HCV infection,chronic liver disease,and atherogenesis are not completely understood.However,it has been hypothesized that HCV may promote atherogenesis and its complications through several direct and indirect biological mechanisms involving HCV colonization and replication within arterial walls,liver steatosis and fibrosis,enhanced and imbalanced secretion of inflammatory cytokines,oxidative stress,endotoxemia,mixed cryoglobulinemia,perturbed cellular and humoral immunity,hyperhomocysteinemia,hypo-adiponectinaemia,insulin resistance,type 2 diabetes and other components of the metabolic syndrome.Understanding these complex mechanisms is of fundamental importance for the development of novel therapeutic approaches to prevent and to treat vascular complications in patients with chronic HCV infection.Currently,it seems that HCV clearance by interferon and ribavirin treatment significantly reduces non-liver-related mortality;moreover,interferon-based treatment appears to decrease the risk of ischemic stroke.

Chronic hepatitis C,atherosclerosis and cardiovascular disease: What impact of direct-acting antiviral treatments?

Hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, among these there is an increased risk of atherosclerosis and cardiovascular disease as well as an increased cardiovascular mortality. Several direct and indirect HCV pro-atherogenic mechanisms have been proposed. HCV lives and replicates within carotid plaques, promoting a local environment of pro-atherogenic factors. In addition, it causes conditions such as insulin resistance, diabetes, hepatic steatosis, cryoglobulinemia and endotoxinemia that are associated with the development of atherosclerosis and cardiovascular disease. Therapeutic regimens based on direct-acting antiviral agents (DAA) are currently available with high efficacy in HCV clearance and improvement of liver disease, but does HCV eradication also improve atherosclerosis and the risk of cardiovascular disease? Recently, a multi-center study has shown that elimination of HCV improves carotid atherosclerosis. Two studies have shown that DAA treatments significantly reduce the risk of cardiovascular events. Several studies have assessed the impact of HCV clearance on pro-atherosclerosis metabolic conditions showing improvement in cardiovascular risk biomarkers, disappearance or improvement of insulin resistance, reduction of risk of developing diabetes and improvement of glycemic control. There are also evidences that HCV clearance promotes the recovery of cytokines and inflammatory markers associated with atherosclerosis and the disappearance of cryoglobulinemia. Available data show that clearance of HCV by DAAs is associated with an improvement in atherosclerosis and metabolic and immunological conditions that promote the development of cardiovascular disease. However, the data are not sufficient to allow definitive conclusions and further studies will be needed to definitively clarify the impact of HCV clearance on atherosclerosis and cardiovascular disease.

Effect of Xiongshao Capsule (芎芍胶囊) on the Function of Vascular Endothelium of Patients with Cervical Atherosclerosis

Objective: To study the effect of Xiongshao Capsule (芎芍胶囊, XSC), a TCM herb that can promote blood circulation to remove blood stasis, on the endothelial dependent relaxation function, serum nitric oxide (NO), and plasma endothelin-KET-1) of the patients with cervical atherosclerosis. Methods: Forty patients were randomly divided into two groups; XSC group and Probucol group (western medicine control). In addition, 20 healthy people were set as a normal control group. Plasma ET-1, serum NO, the internal diameter of basal brachial artery, endothelial dependent flow mediated dilation (FMD) and non-endothelial dependent nitroglycerin induced dilation (NID) to the trial group before and after therapy and to the healthy control group were determined respectively. Results; Compared to the healthy control group, FMD of patients with atherosclerosis was damaged obviously, the serum NO level decreased, plasma ET-1 increased (P< 0. 01), NID also decreased (P<0. 05), the internal diameter of basal brachial artery has no obvious difference (P>0. 05). After the patients with atherosclerosis were treated with Xiongshao Capsule for 12 weeks, FMD increased evidently, plasma ET-1 decreased, serum NO and the ratio of NO/ET-1 increased, compared with the level before therapy and Probucol group, the difference was significant (P<0.05, P<0.01), NID didn't change obviously (P>0.05). Conclusion: XSC could regulate vascular activity factor and improve the function of endothelial dependent vascular dilation of patients with atherosclerosis.

INSULIN RESISTANCE AND CAROTID ATHEROSCLEROSIS IN 221 PATIENTS WITH POTENTIAL HYPERGLYCEMIA

Objective To investigate the relationship between insulin resistance and carotid atherosclerosis in patients with potential hyperglycemia. Methods A total of 221 patients were recruited among those with potential hyperglycemia. All participants underwent physical examination, medical history interview, and 75 g oral glucose tolerance test. Venous blood was sampled for measurement of insulin and cholesterol levels. The intima-media thickness (IMT) in bilateral common carotid arteries was observed by B-mode ultrasound. Insulin resistance index was calculated by homeostasis model assessment (HOMA-IR). Subjects were stratified in quintiles according to HOMA-IR values. Risk factors and atherosclerotic parameters were analyzed. Results With HOMA-IR value increase, incidence of impaired glucose tolerance, diabetes mellitus, hypertension, and coronary artery disease increased, the levels of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting plasma glucose, 2 hour plasma glucose, and fasting insulin increased as well, while the level of high density lipoprotein cholesterol (HDL-C) decreased. Meanwhile, all atherosclerotic parameters increased. Multivariate regression analysis showed that TG, total cholesterol, HDL-C, LDL-C levels, and ln(HOMA-IR) were related to IMT, hence were risk factors for IMT increase. Conclusion Insulin resistance is implicated in atherogenesis.

Atherosclerosis imaging using 3D black blood TSE SPACE vs 2D TSE

AIM: To compare 3D Black Blood turbo spin echo(TSE)sampling perfection with application-optimized contrast using different flip angle evolution(SPACE) vs 2D TSE in evaluating atherosclerotic plaques in multiple vascular territories. METHODS: The carotid, aortic, and femoral arterial walls of 16 patients at risk for cardiovascular or atherosclerotic disease were studied using both 3D black blood magnetic resonance imaging SPACE and conventional 2D multi-contrast TSE sequences using a consolidated imaging approach in the same imaging session. Qualitative and quantitative analyses were performed on the images. Agreement of morphometric measurements between the two imaging sequences was assessed using a two-sample t-test, calculation of the intra-class correlation coefficient and by the method of linear regression and Bland-Altman analyses. RESULTS: No statistically significant qualitative differences were found between the 3D SPACE and 2D TSE techniques for images of the carotids and aorta. For images of the femoral arteries, however, there were statistically significant differences in all four qualitative scores between the two techniques. Using the current approach, 3D SPACE is suboptimal for femoral imaging. However, this may be due to coils not being optimized for femoral imaging. Quantitatively, in our study, higher mean total vessel area measurements for the 3D SPACE technique across all three vascular beds were observed. No significant differences in lumen area for both the right and left carotids were observed between the two techniques. Overall, a significant-correlation existed between measures obtained between the two approaches. CONCLUSION: Qualitative and quantitative measurements between 3D SPACE and 2D TSE techniques are comparable. 3D-SPACE may be a feasible approach in the evaluation of cardiovascular patients.

Hepatic steatosis is associated with an increased risk of carotid atherosclerosis

AIM: Although an association between hepatic steatosis and vascular risk factors has been described, direct relationships between fatty liver and atherosclerosis have not yet been investigated. The aim of the present study has been to investigate those relationships. METHODS: The Study of Health in Pomerania examined a random population sample aged between 20 and 79 years. A study population of 4 222 subjects without hepatitis B and C infections and without liver cirrhosis was available for the present analysis. Hepatic steatosis was defined sonographically and intima-media thickness (IMT) as well as plaque prevalence were estimated by carotid ultrasound. RESULTS: The prevalence rate of hepatic steatosis was 29.9%. Among subjects aged ≥45 years, an association between hepatic steatosis and IMT of the carotid arteries was found in bivariate analysis, but not after adjustment for atherosclerotic risk factors. Individuals with fatty liver had more often carotid plaques than persons without fatty liver (plaque prevalence rate 76.8% vs 66.6%; P<0.001). This association persisted after adjustment for confounding factors and was predominantly present in subjects with no to mild alcohol consumption. CONCLUSION: There is an independent association between hepatic steatosis and carotid atherosclerotic plaques. Metabolic changes due to nonalcoholic fatty liver disease may explain this relationship.

Subclinical atherosclerosis in northern and southern China： the Chinese paradox

Background The incidence of coronary heart disease （CHD） is higher in Northern than that in Southern China, however differences in traditional CHD risk factors do not fully explain this. No study has examined the differences in subclinical atherosclerosis that may help explain the differences in incidence. This study examined these differences in subclinical atherosclerosis using coronary computed tomography （CT） for calcification between the Northern and Southern China. Methods We selected a random sample of participants in a large multi-center ongoing epidemiologic study for coronary calcium scanning in one northern city （North） （Beijing, n = 49） and in two southern cities （South） （Shanghai, n = 50, and Guangzhou, n = 50）. Participants from the three field centers （mean age 67 years） underwent coronary risk factor evaluation and cardiac CT scanning for coronary calcium measurement using the Multi-Ethnic Study of Atherosclerosis scanning protocol. Results Adjusted log-transformed coronary artery calcium score in North China （Beijing） was 3.1 ±0.4 and in South China （Shanghai and Guangzhou） was 2.2 ＋_ 0.3 （P = 0.04）. Mean calcium score for the northern city of Beijing was three times higher than that of the southern city of Guangzhou （P = 0.01） and 2.5 times higher than for the southern city of Shanghai （P = 0.03）. Conclusions The extent of subclinical atherosclerosis is significantly higher in the northern city of Beijing than that in the two southern cities of Guangzhou and Shanghai, even after adjusting for standard cardiac risk factors. This finding suggests that standard risk factors do not fully explain north south differences in clinical CHD incidence.

Glycemic and blood pressure control in older patients with hypertension and diabetes： association with carotid atherosclerosis

Backgroud Numerous studies have confirmed the effectiveness of slowing the progression of atherosclerosis by blood pressure （Bp） control in patients with hypertension and several studies also showed the efficacy of intensive glycemic control in decreasing progression of carotid intima-media thickness （CIMT） in patients with type 1 and type 2 diabetes. However, few studies have compared the relative importance of glycemic w＇. Bp control in patients with diabetes and hypertension. We aimed to investigate the association between Bp and glycemic control and subclinical carotid atherosclerosis in older patients with hypertension and type 2 diabetes. Methods In a cross-sectional study, B-mode high-resolution ultrasonography of the carotid artery was performed in 670 subjects （508 males and 162 females） aged 60 years or over who had self-reported hypertension and diabetes but no history of coronary heart disease or stroke. Subjects were categorized by their systolic blood pressure： tight control, 〈 130 mmHg; usual control, 130-139 mmHg; or uncontrolled, 〉 140 mmHg, and by their hemoglobin Alc （HbAlc） level： tight control, 〈 6.5%; usual control, 6.5%-7.5%; or uncontrolled, 〉 7.5%, respectively. Results The mean CIMT was 8.20 ±0.11 mm, and carotid plaque was found in 52.5% （352/670） subjects. Overall, 62.1% of the subjects had subclinical carotid atherosclerosis, defined as having either carotid plaque or elevated CIMT （≥ 1.1 ram）. The mean CIMT was significantly different between Bp control categories （7.60 ± 0.09 mm, 7.90 ±0.08 mm, and 8.60 ± 0.12 mm, respectively, P = 0.03） but not between glycemic control categories （8.20± 0.10 mm, 8.1 ±0.08 mm, and 8.40 ± 0.14 ram, respectively, P = 0.13） using ANCOVA analysis. Multivariable logistic regression adjusting for potential confounding factors showed that usual or uncontrolled Bp control were associated with having carotid plaque （OR = 1.08 and OR=1.42, respectively）, or elevated CIMT [Odd ratio （OR） = 1.17, 95% confidence interval （CI） 1.04-2.24, and OR = 1.54, 95% CI 1.36-2.96, respectively compared to tight Bp control; but did not show glycemic control as independent predictor of either having carotid plaque or elevated CIMT. Conclusions In older patients with hypertension and diabetes, blood pressure control, but not glycemic control is associated with subclinical carotid atherosclerosis.

The impact of vascular risk factors multiplicity on severity of carotid atherosclerosis—A retrospective analysis of 1969 Egyptian subjects

Background and Purpose: Carotid atherosclerosis has been recognized as a major cause of stroke. The cur-rent study aimed to describe the effect of multiplicity rather than the type of vascular risk factors on severity of carotid atherosclerosis among a large sample of Egyptian population. Methods: We analyzed the data of 1969 Egyptian subjects, who proved to have extra cranial carotid atherosclerotic disease by duplex scanning at the vascular laboratories of Cairo Uni-versity Hospitals. Demographic, clinical data and causes of referral were recorded and correlated with ultrasound findings. Atherosclerotic indices, namely IMT, plaque number and percentage of stenosis were used for evaluation of severity of carotid atherosclerosis. Furthermore, subjects were classified according to multiplicity of major atherosclerotic risk factors and multivariate regression analysis was performed to detect independent predictors of significant carotid disease. Results: Out of 1969 subjects with proved signs of extracranial carotid atherosclerosis by duplex ultrasonographic scan, 225 (11.4%) showed hemody-namic significant stenosis (≥50%). Multiplicity of risk factors beyond the age of 50 years was the strongest predictor of significant stenosis. Conclusion: Age more than 50 years and multiplicity rather than the type of risk factors were the strongest predictors of significant carotid atherosclerotic disease (CAD).

Effects of Pitavastatin on Lipoprotein Subfractions and Oxidized Low-density Lipoprotein in Patients with Atherosclerosis

It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein(LDL)cholesterol(LDL-C),but its impact on lipoprotein subfractions and oxidized low-density lipoprotein(oxLDL)has not been determined.The aim of the present study was to investigate the potential effects of pitavastatin on subfractions of LDL and high-density lipoprotein(HDL)as well as oxLDL in untreated patients with coronary atherosclerosis(AS).Thirty-six subjects were enrolled in this study.O f them,18 patients with AS were administered pitavastatin 2 mg/day for 8 weeks and 18 healthy subjects without therapy served as controls.The plasma lipid profile,lipoprotein subfractions and circulating oxLDL were determined at baseline and 8 weeks respectively.The results showed that pitavastatin treatment indeed not only decreased LDL-C,total cholesterol(TC),triglycerides(TG)and apolipoprotein B(ApoB)levels,and increased HDL cholesterol(HDL-C),but also reduced the cholesterol concentration of all of the LDL subfractions and the percentage of intermediate and small LDL subfractions.Meanwhile,pitavastatin could decrease plasma oxLDL levels.Furthermore,a more close correlation was found between oxLDL and LDL-C as well as LDL subfractions after pitavastatin treatment.We concluded that a moderate dose of pitavastatin therapy not only decreases LDL-C and oxLDL concentrations but also improves LDL subfractions in patients with AS.

Preliminary study of metabonomic changes during the progression of atherosclerosis in miniature pigs

Background:To explore potential biomarkers for early diagnosis of atherosclerosis(AS)and provide basic data for further research on AS,the characteristics of serum metabolomics during the progression of AS in mini-pigs were observed dynamically.Methods:An AS model in Bama miniature pigs was established by a high-cholesterol and high-fat diet.Fasting serum samples were collected monthly for metabolomics and serum lipid detection.At the end of the treatment period,pathological analysis of the abdominal aorta and coronary artery was performed to evaluate the lesions of AS,thereby distinguishing the susceptibility of mini-pigs to AS.The metabolomics was de-tected using a high-resolution untargeted metabolomic approach.Statistical analysis was used to identify metabolites associated with AS susceptibility.Results:Based on pathological analysis,mini-pigs were divided into two groups:a susceptible group(n=3)and a non-susceptible group(n=6).A total of 1318 metabo-lites were identified,with significant shifting of metabolic profiles over time in both groups.Dynamic monitoring analysis highlighted 57 metabolites that exhibited an ob-vious trend of differential changes between two groups with the advance of time.The KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment analysis in-dicated significant disorders in cholesterol metabolism,primary bile acid metabolism,histidine metabolism,as well as taurine and hypotaurine metabolism.Conclusions:During the progression of AS in mini-pigs induced by high-cholesterol/high-fat diet,the alterations in serum metabolic profile exhibited a time-dependent pattern,accompanied by notable disturbances in lipid metabolism,cholesterol me-tabolism,and amino acid metabolism.These metabolites may become potential bio-markers for early diagnosis of AS.