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.

Isoliquiritigenin regulated ox-LDL through activating the PPAR-γ signaling pathway to stabilize atherosclerosis plaques

Objective:To explore the molecular mechanisms of isoliquiritigenin in stabilizing atherosclerotic plaques by activating PPAR-γsignal pathway to regulate ox-LDL metabolism.Methods:The ApoE-/-mice AS carotid plaque model was prepared by using high fat diet and right perivascular carotid collar placement(PCCP).ApoE-/-mice were randomly divided into the model group and the isoliquiritigenin group after PCCP.C57BL/6J mice were used for the control group.High fat diet continued feeding for 8 weeks after PCCP to establish the AS model.Automatic biochemical analyzer was used to test levels of total cholesterol(TC),triacylglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C).ELISA was used to measure oxidized low-density lipoprotein(ox-LDL)in serum.Hematoxylin-eosin(HE)staining was used to observe the pathological pattern of the carotid artery,and then calculated the carotid parameters.Oil red O staining was used for lipid determination,Masson staining was used to determine collagen content,MOMA-2 andα-SMA immunohistochemical staining were used to determine macrophages and smooth muscle cells,and to calculate the vulnerability index.Western blot was used to detected the expression of PPAR-γ,LXR-α,FABP-4,MMP-2 and MMP-9 in mice arteries.Results:Compared with the normal group,TC、TG、LDL-C、HDL-C and ox-LDL were increased in the model group.Compared with the model group,TC、TG、LDL-C and ox-LDL were reduced,and there was no significant change in HDL-C of the isoliquiritigenin group.Compared with the normal group,intima thickness(IT),intima/media thickness(IT/MT),plaque area(PA),and plaque area/lumen area(PA/LA)of carotid arteries were increased,the content of lipid and MOMA-2 in plaques was increased,collagen andα-SMA content decreased,and the vulnerability index was higher in the model group.The expression of PPAR-γand LXR-αwere reduced and the expression of FABP-4,MMP-2 and MMP-9 were increased in the model group.Compared with the model group,carotid IT,IT/MT,PA,and PA/LA were reduced,the content of lipid and MOMA-2 in plaques was decreased,collagen andα-SMA content were increased,and the vulnerability index was decreased in the isoliquiritigenin group.PPAR-γand LXR-αexpression were increased,FABP-4,MMP-2 and MMP-9 expression were decreased significantly in the isoliquiritigenin group.Conclusion:Isoliquiritigenin can exert anti-AS effects by activating PPAR-γ,up-regulating LXR-α,reducing FABP-4 expression,reducing ox-LDL,reducing the protein expression of MMP-2 and MMP-9,decreasing plaque vulnerability index,and increasing plaque stability.

MicroRNA Let-7g and Atherosclerosis Plaque Stabilization

Vascular atherosclerotic vulnerable plaque rupture is the primary cause of acute myocardial infarctions and strokes. Thus, stabilization of vulnerable plaques is of important clinical endeavor to decrease the fatal risk of atherosclerosis. Inflammatory infiltration, apoptosis of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), destruction of extracellular matrix (ECM) or collagen, and neovascularization all contribute to the formation and stability of plaque. Let-7g, one miRNA of let-7 family, is related to retardation of the progress of vulnerable atherosclerosis plaque. First of all, let-7g induced preservation on vascular diseases through regulating on the intracellular Ca2+- activated protein kinase C-oxLDL-LOX-1 pathway, which resulted in reduced leukocyte adhesion to and migration across endothelium. Over expression of let-7g negatively regulated apoptosis in the ECs by targeting lectin-like oxidized LDL receptor-1(LOX-1)/CASP3 expression, therefore made the fibrous cap of plaque integrated and thick, increased the density of vascular atherosclerotic plaque. In addition, let-7g might stabilize the atherosclerotic plaque through other aspects. In this review, we focus on current and potential importance of let-7g on the stabilization of atherosclerosis plaque which might lead to the future development of an alternative strategy of CAD.

Effects of different statins application methods on plaques in patients with coronary atherosclerosis

BACKGROUND Discontinued application of statins may be related to adverse cardiovascular events.However,it is unclear whether different statins administration methods have effects on coronary artery plaques.AIM To evaluate the effects of different statins application methods on plaques in patients with coronary atherosclerosis.METHODS A total of 100 patients diagnosed with atherosclerotic plaque by coronary artery computed tomography were continuously selected and divided into three groups according to different statins administration methods(discontinued application group,n=32;intermittent application group,n=39;sustained application group,n=29).The effects of the different statins application methods on coronary atherosclerotic plaque were assessed.RESULTS The volume change and rate of change of the most severe plaques were significantly reduced in the sustained application group(P≤0.001).The volume change of the most severe plaques correlated positively with low-density lipoprotein(LDL-C)levels only in the sustained application group(R=0.362,P=0.013).There were no changes in plaques or LDL-C levels in the intermittent and discontinued application groups.CONCLUSION Continuous application of statins is effective for controlling plaque progression,whereas discontinued or intermittent administration of statins is not conducive to controlling plaques.Only with continuous statins administration can a reduction in LDL-C levels result in plaque volume shrinkage.

Expression and Location of Intracellular Tissue Factor in Atherosclerosis Stable Plaque of ApoE^(-/-) Mice

In the ApoE^-/- mouse model of atherosclerosis （AS） stable plaque, the expression and location of intracellular tissue factor （TF） in the cellular components of AS stable plaque were investigated in order to explore the cellular mechanism of AS thrombosis. Pathological changes of the stable plaque were observed under a microscope. The expression of TF protein was examined in aortic stable plaque of mice by using immunohistochemistry. Color image planimetric system was used to analyze the histological components of the stable plaque and the TF distribution. Under the confocal microscope, the intracellular TF location in the stable plaque of mice was observed. The results showed the cellular area was the major part of stable plaque （67.36%±6.52%, P〈0.01）. The percentage of total area occupied by cellular area was significantly larger than atheromatous gruel and acellular area （P〈0.01）. Macrophages and smooth muscle cells （SMC） were major cells in the cellular area. The percentage of total area occupied by SMC was significantly larger than by macrophages （P〈0.01）. Multiple linear regression analysis showed there was a positive correlation between TF area and SMC area （r=0.616, P=-0.008）, and no correlation was found between TF area and macrophage area （r=0.437, P=0.08）. Pictures of color image planimetric analysis of TF and SMC were merged to highlight areas with co-localization （yellow）, it was concluded that the process could be a cell-mediated TF expression in the stable plaque. SMC may be the major source of TF in AS without plaque rupture.

Correlation of carotid contrast-enhanced ultrasonography parameters with nerve damage and plaque properties in patients with atherosclerosis cerebral infarction

Objective: To explore the correlation of carotid contrast-enhanced ultrasonography parameters with nerve damage and plaque properties in patients with atherosclerosis cerebral infarction. Methods: A total of 176 patients with atherosclerosis cerebral infarction who were sent to this hospital for medical treatment between August 2014 and February 2018 were enrolled in cerebral infarction group, and 100 healthy elderly subjects who received physical examination in this hospital during the same period were enrolled in normal control group. Carotid CEUS parameter levels as well as serum contents of indexes related to nerve injury and plaque property were compared between the two groups, and Pearson test was used to evaluate the correlation of CEUS parameters levels with nerve damage and plaque properties in patients with cerebral infarction. Results: CEUS parameter Tp level in cerebral infarction group was lower than that in normal control group whereas P and AUC levels were higher than those in normal control group;serum nerve damage-related indexes SAA, NT-proBNP, Hcy, NSE and copeptin contents were higher than those of normal control group;serum plaque property-related indexes Lp-PLA2, MMP-9, Cat S and CD62P contents were higher than those of normal control group while APN and Cys C contents were lower than those of normal control group. Correlation analysis confirmed that carotid CEUS parameter levels in patients with cerebral infarction were correlated with the contents of indexes related to nerve damage and plaque property. Conclusion: Carotid CEUS parameters are obviously abnormal in patients with atherosclerosis cerebral infarction, they are directly correlated with the specific nerve damage and plaque properties, and they can be used as the reliable indexes to forecast the risk of cerebral infarction and evaluate its severity.

Effect of ginkgo capsules combined with secondary preventive drugs on the endothelial injury and plaque properties of patients with hypertension complicated by carotid atherosclerosis

Objective: To study the effect of ginkgo capsules combined with secondary preventive drugs on the endothelial injury and plaque properties of patients with hypertension complicated by carotid atherosclerosis. Methods: A total of 178 patients with hypertension complicated by carotid atherosclerosis who were treated in Chengyue Community Health Service Center of Xisaishan District Huangshi City Hubei Province between February 2015 and January 2017 were collected and randomly divided into two groups. Control group were treated with conventional secondary preventive drugs, and observation group were treated with ginkgo capsules combined with secondary preventive drugs. The differences in serum endothelial injury indexes and lipid metabolism indexes as well as carotid artery ultrasound parameters were compared between the two groups before and after treatment. Results: Before treatment, endothelial injury indexes and lipid metabolism indexes as well as carotid artery ultrasound parameters were not significantly different between two groups. After treatment, serum ET, AngⅡ, TC, LDL-C and LpA contents as well as carotid artery ultrasound parameters DS and AS levels of observation group were lower than those of control group while serum NO and HDL-C contents as well as carotid artery ultrasound parameter MLD level were higher than those of control group. Conclusion: Ginkgo capsule combined with secondary preventive drugs can effectively reduce the endothelial injury and stabilize the plaques in patients with hypertension complicated by carotid atherosclerosis.

Effect of butylphthalide soft capsule on the anti-inflammatory effect and plaque stability in patients with ischemic cerebrovascular disease and carotid atherosclerosis

Objective:To explore the effect of butylphthalide soft capsule on the serum hs-CRP, MMP-9, and TNF-α in patients with ischemic cerebrovascular disease in order to evaluate the the therapeutic effect in the treatment of carotid atherosclerosis.Methods:According to the carotid ultrasound results, the patients were divided into the stable plaque group (control group) and the vulnerable plaque group. The patients in the vulnerable plaque group were randomized into the intervention 1 group and intervention 2 group. The patients in the two subgroups were given bayaspirin and atorvastatin. On this basis, the patients in the intervention 1 group were given butylphthalide soft capsules. The serum hs-CRP, MMP-9, and TNF-αbefore treatment and 6 months after treatment in each group were detected. The color Doppler ultrasound was used to measure and evaluate IMT, Crouse score, and plaque echo change. Results: The serum hs-CRP, MMP-9, and TNF-α levels before treatment between the two subgroups were significantly higher than those in the control group, but the comparison between intervention 1 group and intervention 2 group was not statistically significant. The serum hs-CRP, MMP-9, and TNF-α levels 6 months after treatment in the two subgroups were significantly reduced when compared with before treatment. The serum hs-CRP, MMP-9, and TNF-α levels after treatment in the intervention 1 group were significantly lower than those in the intervention 2 group. IMT 6 months after treatment in the two subgroups was significantly reduced when compared with before treatment. The reduced degree of IMT after treatment in the intervention 1 group was significantly greater than that in the intervention 2 group. Crouse score after treatment in the two subgroups was significantly reduced when compared with before treatment, but the comparison between the two groups was not statistically significant. The unstable plaque number after treatment in the two subgroups was significantly reduced when compared with before treatment. The unstable plaque number after treatment in the intervention 1 group was significantly lower than that in the intervention 2 group.Conclusions:Butylphthalide soft capsule can resist the inflammation, reverse the prolieration of carotid intima, stabilize the vulnerable plaque, and remove the non-atherosclerotic plaque.

Relationship between serum inflammatory response cytokines and the change of plaque properties in patients with H-type hypertension complicated by carotid atherosclerosis

Objective:To study the relationship between serum inflammatory response cytokines and the change of plaque properties in patients with H-type hypertension complicated by carotid atherosclerosis.Methods: Patients who were diagnosed with H-type hypertension complicated by carotid atherosclerosis in Yulin Hospital of Traditional Chinese Medicine between May 2014 and December 2016 were selected as group A, patients with H-type hypertension complicated by carotid atherosclerosis and normal Hcy levels were selected as group B, patients with carotid atherosclerosis and normal blood pressure levels and Hcy levels were selected as group C, and healthy volunteers during the same period were selected as control group. Serum levels of inflammatory response cytokines and plaque property-related cytokines were detected.Results: Serum Hcy, sICAM-1, MCP-1, YKL-40, IL-6, PTX3, FGF23, MMP9 and Caspase-3 levels of group A, group B and group C were significantly higher than those of group D, serum Hcy, sICAM-1, MCP-1, YKL-40, IL-6, PTX3, FGF23, MMP9 and Caspase-3 levels of group A and group B were significantly higher than those of group C, and serum Hcy, sICAM-1, MCP-1, YKL-40, IL-6, PTX3, FGF23, MMP9 and Caspase-3 levels of group A were significantly higher than those of group B;serum Hcy, sICAM-1, MCP-1, YKL-40, IL-6, PTX3, FGF23, MMP9 and Caspase-3 levels of group A with vulnerable plaques were significantly higher than those of patients with stable plaques. Serum Hcy, sICAM-1, MCP-1, YKL-40 and IL-6 levels of group A were positively correlated with PTX3, FGF23, MMP9 and Caspase-3 levels.Conclusion: Serum inflammatory response cytokine secretion increases in patients with H-type hypertension complicated by carotid atherosclerosis, and it can result in the change in plaque properties and the decrease in stability.

Effect of folic acid combined with routine drugs on Hcy metabolism, inflammatory response and plaque properties in patients with H-type hypertension complicated by carotid atherosclerosis

Objective:To explore the effect of folic acid combined with routine drugs on Hcy metabolism, inflammatory response and plaque properties in patients with H-type hypertension complicated by carotid atherosclerosis.Methods: A total of 68 patients with H-type hypertension complicated by carotid atherosclerosis who received treatment in our hospital between January 2014 and September 2016 were collected and divided into control group (n=34) and observation group (n=34) according to random number table. The control group received routine therapy and the observation group received folic acid combined with routine drug therapy. The differences in Hcy metabolism, inflammatory response and plaque properties were compared between the two groups of patients before and after treatment.Results:Before treatment, differences in serum Hcy contents, pro-inflammatory and anti-inflammatory mediator contents, and ultrasound plaque property parameter levels were not statistically significant between two groups of patients. After treatment, serum Hcy content of observation group was lower than that of control group;serum pro-inflammatory factors IL-1, IL-6, IL-8 and CRP contents were lower than those of control group;serum anti-inflammatory factors IL-4, IL-10 and IL-13 contents were lower than those of control group;ultrasound plaque property parameter strain value was lower than that of control group while plaque strain rate was higher than that of control group.Conclusion:Folic acid treatment based on routine treatment can effectively accelerate the Hcy metabolism, reduce systemic inflammatory response and increase the plaque stability in patients with H-type hypertension complicated by carotid atherosclerosis.

Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.

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.

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.

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.

Life's essential 8 and risk of subclinical atherosclerosis progression: a prospective cohort study

BACKGROUND Previous studies have demonstrated the benefits of ideal cardiovascular health(CVH) in reducing cardiovascular risk.However,its role in subclinical atherosclerosis(SA) progression remains unclear.We aim to examine the association of CVH,estimated by the American Heart Association's new Life's Essential 8(LE8),with the progression of SA.METHODS This prospective cohort study was conducted among 972 asymptomatic Chinese participants and followed up for5.7 years.The LE8 score(range,0–100) consisted of blood pressure,lipids,glucose,body mass index,smoking status,diet health,physical activity and sleep health was evaluated in 1998 and 2008–2009.Progression of SA was determined by carotid plaque and coronary artery calcification(CAC) in 2008–2009 and 2013–2014.Log-binomial regression model was used to estimate the association of LE8 score with SA progression.RESULTS Each 10 points increment in LE8 score was associated with 15.2%(RR:0.848,95% CI:0.797–0.902),17.7%(RR:0.823,95% CI:0.766–0.884) and 12.0%(RR:0.880,95% CI:0.845–0.916) lower risks of carotid plaque,CAC and overall SA progression,respectively.Compared with participants with non-ideal CVH at both visits,the participants with ideal CVH at both visits had39.1%(RR:0.609,95% CI:0.494–0.752),41.0%(RR:0.590,95% CI:0.456–0.764) and 29.7%(RR:0.703,95% CI:0.598–0.825) lower risks of carotid plaque,CAC and overall SA progression,respectively.CONCLUSIONS Higher LE8 scores were associated with lower risks of SA progression.Besides,long-term maintenance of optimal CVH was more beneficial to prevent SA progression.

An overview of potential cardioprotective benefits of xanthophylls in atherosclerosis:an evidence-based review

Atherosclerosis,as the most prevalent form of cardiovascular disease,is characterized by oxidized lowdensity lipoprotein(ox-LDL)accumulation in the vascular wall,increased inflammation of the large arteries,dysfunction of the endothelial cells(ECs)and vascular smooth muscle cells(VSMCs),which may eventually lead to the formation of plaques.Xanthophylls,one of the main groups of carotenoids,have been proposed as preventive agents or adjunct therapies to prevent and slow the progression of atherosclerosis due to their cardioprotective properties.However,the underlying preventive mechanism of action of xanthophylls on the pathogenesis of atherosclerosis remains unclear,and clinical evidence of the effect of xanthophylls on atherosclerosis have not yet been summarized and critically reviewed.In this regard,we conducted a comprehensive literature search in four scientific databases(Pub Med,Google Scholar,Science Direct and Web of Science)and carefully analyzed the existing evidence to provide meaningful insights on the association between xanthophylls and atherosclerosis from various aspects.Based on the evidence from in vitro and in vivo studies,we explored several potential mechanisms,including antioxidant effect,anti-inflammatory effect,regulation of lipid metabolism,and modulation of ECs and VSMCs dysfunction,and we found that a clear picture of regulatory pathways of xanthophylls on atherosclerosis prevention and treatment is still lacking.In addition,epidemiological studies suggested the possible relationship among high dietary intake of xanthophylls,high plasma/serum xanthophylls and a reduced risk of atherosclerosis.Direct evidence from interventional studies investigating the effect of xanthophylls on atherosclerosis is very sparse,whilst indirect clinical evidence was only limited to astaxanthin and lutein.Therefore,well-designed long-term randomized controlled trials(RCTs)are highly recommended for future studies to investigate the effective dose of different xanthophylls on atherosclerosis prevention and their possible ancillary effect in conjunction with drug therapies on different stages of atherosclerosis.

Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis:Current Knowledge and Future Perspectives

Atherosclerosis(AS)is characterized by impairment and apoptosis of endothelial cells,continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells,which is documented as the traditional cellular paradigm.However,the mechanisms appear much more complicated than we thought since a bulk of studies on efferocytosis,transdifferentiation and novel cell death forms such as ferroptosis,pyroptosis,and extracellular trap were reported.Discovery of novel pathological cellular landscapes provides a large number of therapeutic targets.On the other side,the unsatisfactory therapeutic effects of current treatment with lipid-lowering drugs as the cornerstone also restricts the efforts to reduce global AS burden.Stem cell-or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse effects.Given the complexity of pathological changes of AS,attempts to develop an almighty medicine based on single mechanisms could be theoretically challenging.In this review,the top stories in the cellular landscapes during the initiation and progression of AS and the therapies were summarized in an integrated perspective to facilitate efforts to develop a multi-targets strategy and fill the gap between mechanism research and clinical translation.The future challenges and improvements were also discussed.

Sonodynamic therapy for the treatment of atherosclerosis

Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and stabilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDT's therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.

Atherosclerosis originating from childhood:Specific features

Atherosclerosis is extremely widespread.Traditionally,it is considered a disease of older people,who most often experience problems with the heart and blood vessels.While much attention from the scientific community has been paid to studying the association between aging and atherosclerosis,as well as its consequences,there is evidence that atherosclerosis occurs at an early age.Atherosclerosis may form both during intrauterine development and in childhood.Nutrition plays an important role in childhood atherosclerosis,along with previous infectious diseases and excess weight of both the child and the mother.In the present review,we examined the development of atherosclerosis and the prerequisites in childhood.

Analysis of a New Toothbrushing Technique through Plaque Removal Success

Background/Aims: Determining the levels of oral health and the quality of dental care are fundamental to building concepts of oral health. This study aims to assess toothbrushing techniques using a technical and physical model, clarifying how children and pre-adults learn to brush their teeth. Materials and Methods: Data were recorded from 23 participants, both male and female of various ages, using a proposed electronic toothbrush equipped with X-Y-Z axes pathways. The data, collected before and after training experiments, were processed with MATLAB to generate plots for the three axes. Results: The study revealed that most parameter values, such as Mean Difference Between Amplitudes (MAV, 6.00), Wilson Amplitude (WAMP, 179.419), and Average Amplitude Coupling (AAC, 1.270), decreased from before to after the experiments. Furthermore, the average overall epoch lengths (AVG) showed a 75% reduction in movement amplitude between the two experiments. Conclusion: Dentist observations indicated which brushing methods were acceptable or not. Analytical values suggest that individuals learn the toothbrushing technique effectively, and medical observations clearly demonstrate the success of the proposed method.