Artery Atherosclerotic Lesions Research Articles

Outcomes of Excimer Laser Ablation Combined with Drug-coated Balloon in Atherosclerotic Lesions of the Popliteal Artery

BackgroundThe treatment of atherosclerotic lesions in the popliteal artery is challenging. This study aims to investigate the efficacy and safety of excimer laser ablation (ELA) combined with drug-coated balloon (DCB) for these lesions. MethodsFrom June 2019 to December 2021, data of patients who underwent ELA combined with DCB in the popliteal artery were retrospectively reviewed. Demographics, lesion characteristics, periprocedural complications and follow-up information were analyzed. The primary endpoint was primary patency. Secondary endpoints included major amputation-free survival (MAFS) rate, technical success, bailout stenting, clinically-driven target lesion reintervention (CD-TLR), improvement of ankle-brachial index (ABI) and Rutherford class. ResultsA total of 61 patients were enrolled. The mean age was 73.4 ± 11.7 years. 20 (32.8%) patients had stenotic lesions while 41 (67.2%) patients had chronic total occlusions (CTOs). The mean length of these lesion was 7.3 ± 2.8 cm. Procedure technical success rate was 95.1%. Bailout stent was performed in 3 (4.9%) patients. Intraprocedural distal embolization occurred in 3 (4.9%) patients, while flow limiting dissections occurred in 3 (4.9%) patients. The mean ABI was significantly improved from 0.45 ± 0.13 at baseline to 0.90 ± 0.12 after ELA, 0.88 ± 0.11 at 6 months and 0.85 ± 0.12 at 12 months. during the follow-up period. The median follow-up time was 28.2 ± 6.1 months. Reintervention was performed in 5 (8.2%) patients. The 2-year primary patency was 83.5%. ConclusionELA combined with DCB is a safe and effective strategy in the treatment of popliteal artery atherosclerotic lesions with low rates of bail-out stenting and high primary patency.

The role of the gut microbiota in the development of coronary artery atherosclerosis

Cardiovascular diseases are one of the most common causes of death in the Russian Federation and worldwide. Consistently high statistical values, despite known risk factors, encourage us to look for new aspects of the etiology, pathogenesis and course of this group of diseases. The group of coronary heart disease requires special attention, most of the nosologies of which are diseases associated with atherosclerotic lesions of the coronary arteries. Despite the well-established concept of the pathogenesis of atherosclerosis associated with the response to endothelial damage, there is more and more data on the participation of gut microbiota metabolites in the occurrence and progression of this process, which has formed into the theory of atherogenic microbiome. The main bacterial factors influencing the pathogenesis of atherosclerosis are considered to be such metabolites as trimethylamine-N-oxide, lipopolysaccharide, short-chain fatty acids, and deoxyribonucleic acid. They take part in changes in lipid metabolism and immunological reactivity of the macroorganism, induce low-grade inflammation, which leads to the progression of atherosclerotic lesions of arteries, including coronary arteries. The purpose of this review is to analyze the literature on the role of the gut microbiota in the pathogenesis of coronary artery atherosclerosis, its effect on lipid metabolism, the relationship between changes in the microbiome and the development of atherosclerotic vascular lesions, and features of the atherogenic microbiome. Literature search was carried out in PubMed and Google Scholar systems among full-text articles published in Russian and English until January 2023 for the keywords: atherosclerosis, gut microbiota, cardiovascular diseases.

Mitochondrial dysfunction and metabolic reprogramming induce macrophage pro-inflammatory phenotype switch and atherosclerosis progression in aging.

Aging increases the risk of atherosclerotic vascular disease and its complications. Macrophages are pivotal in the pathogenesis of vascular aging, driving inflammation and atherosclerosis progression. NOX4 (NADPH oxidase 4) expression increases with age, correlating with mitochondrial dysfunction, inflammation, and atherosclerosis. We hypothesized that the NOX4-dependent mitochondrial oxidative stress promotes aging-associated atherosclerosis progression by causing metabolic dysfunction and inflammatory phenotype switch in macrophages. We studied atherosclerotic lesion morphology and macrophage phenotype in young (5-month-old) and aged (16-month-old) Nox4 -/-/Apoe -/- and Apoe -/- mice fed Western diet. Young Nox4-/-/Apoe-/- and Apoe-/- mice had comparable aortic and brachiocephalic artery atherosclerotic lesion cross-sectional areas. Aged mice showed significantly increased lesion area compared with young mice. Aged Nox4-/-/Apoe-/- had significantly lower lesion areas than Apoe-/- mice. Compared with Apoe-/- mice, atherosclerotic lesions in aged Nox4-/-/Apoe-/- showed reduced cellular and mitochondrial ROS and oxidative DNA damage, lower necrotic core area, higher collagen content, and decreased inflammatory cytokine expression. Immunofluorescence and flow cytometry analysis revealed that aged Apoe-/- mice had a higher percentage of classically activated pro-inflammatory macrophages (CD38+CD80+) in the lesions. Aged Nox4-/-/Apoe-/- mice had a significantly higher proportion of alternatively activated pro-resolving macrophages (EGR2+/CD163+CD206+) in the lesions, with an increased CD38+/EGR2+ cell ratio compared with Apoe-/- mice. Mitochondrial respiration assessment revealed impaired oxidative phosphorylation and increased glycolytic ATP production in macrophages from aged Apoe-/- mice. In contrast, macrophages from Nox4-/-/Apoe-/- mice were less glycolytic and more aerobic, with preserved basal and maximal respiration and mitochondrial ATP production. Macrophages from Nox4-/-/Apoe-/- mice also had lower mitochondrial ROS levels and reduced IL1β secretion; flow cytometry analysis showed fewer CD38+ cells after IFNγ+LPS treatment and more EGR2+ cells after IL4 treatment than in Apoe-/- macrophages. In aged Apoe-/- mice, inhibition of NOX4 activity using GKT137831 significantly reduced macrophage mitochondrial ROS and improved mitochondrial function, resulting in decreased CD68+CD80+ and increased CD163+CD206+ lesion macrophage proportion and attenuated atherosclerosis. Our findings suggest that increased NOX4 in aging drives macrophage mitochondrial dysfunction, glycolytic metabolic switch, and pro-inflammatory phenotype, advancing atherosclerosis. Inhibiting NOX4 or mitochondrial dysfunction could alleviate vascular inflammation and atherosclerosis, preserving plaque integrity.

DIAGNOSIS AND TREATMENT OF PERIPHERAL ARTERIAL DISEASE IN PATIENTS WITH DIABETES MELLITUS

Patients with endocrine disorders often present with concomitant cardiovascular diseases. Peripheral arterial disease (PAD) in individuals with type 2 diabetes exhibits various clinical characteristics and diverse consequences. One of its primary manifestations is macrovascular complications. Although atherosclerosis is the primary cause, other contributory factors come into play. Notably, individuals with diabetes experience a more severe clinical course, marked by higher amputation rates and significant differences in mortality. The ankle-brachial index (ABI) is the standard diagnostic tool for identifying arterial diseases, while angiography is considered the gold standard for assessing anatomical aspects. Effective management of comorbidities including type 2 diabetes, hypertension, and dyslipidemia, has a substantial impact on clinical progression. Atherosclerotic disease manifests through the narrowing of affected vessels, resulting in reduced blood flow. The diagnosis of PAD requires the management of risk factors, medication-based therapies, and interventions for lower extremity issues. Physical exercise is also a valuable approach for alleviating PAD symptoms and extending pain-free walking distances. For patients with refractory conditions, surgical interventions are recommended. In cases where atherosclerotic arterial lesions are minor, pose minimal surgical risk, and have a high likelihood of successful intervention, percutaneous transluminal angioplasty should be considered. Early intervention is recommended in the presence of rest pain, ischemic ulcers, or necrosis. Balloon angioplasty and stent placement have shown efficacy in symptom relief for many PAD patients. Recent technological advancements have expanded the use of endovascular procedures, even before considering traditional "open" methods. Lesion location and length are essential factors for the long-term success of percutaneous vascular interventions.

Triglyceride-glucose index is associated with severe obstructive coronary artery disease and atherosclerotic target lesion failure among young adults

BackgroundEarly diagnosis and treatment effectiveness of early-onset coronary artery disease (EOCAD) are crucial, and non-invasive predictive biomarkers are needed for young adults. We aimed to evaluate the usefulness of the triglyceride-glucose (TyG) index, a novel marker of insulin resistance, in identifying young CAD patients and predicting their risk of developing target lesion failure (TLF).MethodsWe recruited EOCAD patients (luminal narrowing ≥ 70%) and controls free from CAD (luminal narrowing < 30%), both aged 45 years or younger, from 38 hospitals in China between 2017 and 2020. EOCAD patients who underwent successful percutaneous coronary intervention were followed for incident TLF. TyG index was defined as Ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. We used logistic regression and Cox proportional hazards modeling to evaluate the association of TyG index with prevalent EOCAD and incident TLF, respectively. The discriminatory ability of TyG index was assessed by the area under the receiver-operating characteristic curve (AUC).ResultsAmong the included 1513 EOCAD patients (39.6 ± 4.4 years, 95.4% male) and 1513 age-matched controls (39.0 ± 4.4 years, 46.4% male), TyG index was positively associated with the prevalence of EOCAD (adjusted odds ratio: 1.40, 95% confidence interval [CI] 1.23–1.60, per standard deviation [SD] increase in TyG index). The addition of TyG index to an empirical risk model provided an improvement in diagnostic ability for EOCAD, with a net reclassification improvement of 0.10 (95% CI 0.03–0.17, p = 0.005). During a medium of 33 month (IQR: 31–34 months) follow-up, 43 (3.3%) patients experienced TLF. Multivariate Cox regression model revealed that TyG index was an independent risk factor for TLF (adjusted hazard ratio [HR]: 2.410, 95% CI 1.07–5.42 comparing the top to bottom TyG index tertile groups; HR: 1.30, 95% CI 1.01–1.73, per SD increase in TyG index). Compared with a model of conventional risk factors alone, the addition of the TyG index modestly improved the AUC (0.722–0.734, p = 0.04) to predict TLF.ConclusionsTyG index is positively associated with prevalent EOCAD and incident TLF. TyG index appeared to be a valuable component of future efforts to improve CAD risk stratification and TLF outcome prediction among young adults.

Prognosis of Early Outcomes after Isolated Coronary Bypass Surgery: Results of a Single-Center Cohort Study

Background. The importance of predictors of adverse outcomes after coronary bypass surgery needs to be regularly review in view of changing standards of practice. Predicting complications will help reduce current mortality and morbidity among patients who have undergone coronary bypass surgery (CABG). Aims prediction and determination of independent predictors of in-hospital mortality after CABG based on the results of preoperative examination. Methods. In a retrospective cohort single-center study, we analyzed the results of 2239 patients who underwent isolated CABG for the period from September 2018 to August 2021. The primary endpoint of the study was hospital death after CABG. Also, the frequency of: non-fatal myocardial infarction, non-fatal stroke, acute heart failure, postoperative rhythm and conduction disorders, acute renal failure, multiple organ failure, infectious complications was analyzed. Next, we searched for independent predictors and built a prognostic model for assessing the risk of death after CABG. Results. Results. Hospital mortality among patients was 1.34% (n = 30). Independent predictors of death after CABG were: ejection fraction (OR 0.91; 95% CI: 0.880.93; p 0.001), body mass index (OR 0.90; 95% CI: 0.820.99; p = 0.035), glomerular filtration rate (OR 0.97; 95% CI: 0.960.99; p = 0.005), repeated CABG (OR 9.3; 95% CI: 2.7431.24; p 0.001), critical atherosclerotic lesion of the arteries of the lower extremities (OR 4.5; 95% CI: 1.93310.268; p 0.001). The model for predicting the probability of death after CABG had high quality metrics: ROC-AUC 0.838 (95% CI: 0.7470.929; p 0.001), sensitivity 72.4%, specificity 84%. The threshold value of the logistic function P at the cut-off point, which corresponded to the highest value of the Yuden index, was 0.015. The outcome was predicted when the value of the logistic function P was higher than or equal to this value. Conclusion. We have developed a model for predicting in-hospital mortality after CABG based on independent linear predictors: left ventricular ejection fraction, body mass index, glomerular filtration rate, repeated CABG, critical atherosclerotic lesion of the main arteries of the lower extremities.

Preclinical atherosclerotic burden in carotid and lower extremity arteries in adults with congenital heart disease.

Background: Over 90% of patients with congenital heart defects now reach adulthood, due to significant medical advances in recent decades. With advancing age, the risk of acquired cardiovascular diseases increases in addition to the already existing risk due to the congenital defect. The aim of this study was to evaluate the prevalence of atherosclerotic lesions in carotid and lower extremity arteries in adults with congenital heart disease (ACHD). Patients and methods: A total number of 108 ACHD patients (40.6±15.0 years, 50.0% male) and 22 healthy controls (39.3±16.6 years, 40.9% male) were included in this prospective study and underwent a comprehensive angiological examination that included vascular strain analysis on the common carotid artery. Results were stratified by the underlying ACHD lesion groups: shunt lesions (n=26), left-sided obstructive lesions (n=29), right-sided lesions (n=26) and complex lesions (n=27). Results: Colour-coded duplex sonography revealed atherosclerotic lesions in lower extremity arteries in 19 ACHD patients (17.6%). This prevalence did not significantly differ from the one assessed in controls (13.6%, p=0.77). All cases were asymptomatic and therefore classified as Fontaine stage I. 20.4% of ACHD patients presented atherosclerotic lesions in extracranial carotid arteries; amongst controls, the corresponding proportion was 18.4% (p=1.00). No significant differences were observed in atherosclerotic burden in extracranial carotid and lower limb arteries across the four ACHD patient groups (p=0.67 and p=0.89, respectively). Vascular strain analysis revealed no differences between patients and controls. Though circumferential strain varied over ACHD groups (p<0.05), comparison of strain measurements across all specific underlying defect subgroups revealed no significant difference for any of the studied strain parameters. Conclusions: ACHD patients present an atherosclerotic burden in extracranial carotid and lower limb arteries and a vascular stiffness that is comparable to healthy controls.

Abstract 709: Implementation Of Ribosomal Tagging Strategies To Analyze Smooth Muscle Specific Rna Expression In Mouse Models Of Atherosclerosis

Background: Atherosclerotic cardiovascular disease (CVD) is the leading cause of mortality worldwide. Smooth muscle cells (SMCs) make up the bulk of the healthy arterial wall and atherosclerotic lesions. During atherosclerosis progression, we and others have reported on the emergence of multiple harmful and protective types of SMC-derived cell types (SDCs) in lesions, and the use of fluorescence lineage-tracing animal models have made it possible to isolate and analyze cell-type specific transcriptomes by flow cytometry and scRNA-seq. However, these manipulations are known to carry risk for artifacts, alter transcription, and introduce cell type bias. Therefore, alternative approaches that circumvent the need for single cell isolation may be beneficial. Hypothesis: Introduction of an isolation-free method for SMC translatome retrieval may be beneficial in confirming the presence of SDCs correlating with disease. Methods: SMC-specific translatomes were isolated by immunoprecipitation (IP) of epitope-tagged ribosomes from the aortic arch following the “RiboTag approach” developed by McKnight et al. and sequenced to test against libraries created by flow isolation of SMCs and bulk RNA-sequencing. Results: Here we report the creation of SMC-specific atherosclerotic RiboTag mouse model and initial efforts made to assess the SMC/SDC translatome during atherosclerosis. Side-by-side comparison of translatomes isolated by IP from the aortic arch and transcriptomes from sorted SDCs will be used to identify advantages and disadvantages of the respective approaches. Conclusions: This work will determine if and how the use of cell isolation may impact the transcriptome of SMCs and SDCs from mouse atherosclerotic models and establish if translatome analysis of these cell types can be used to complement standard sort-based profiling strategies in the study of atherosclerosis.

Periprocedural Outcomes of Rotational Atherectomy-Assisted Balloon Angioplasty in Isolated Atherosclerotic Popliteal Artery Lesions: The ISO-POP Trial.

Treatment of calcified popliteal artery lesions represents an ongoing challenge for vascular specialists. Biomechanical forces of external compression, torsion and elongation that occur with locomotion in the popliteal segment can lead to stent fractures and occlusions. The aim of our study was to assess the procedural success rate of atherectomy in combination with balloon angioplasty for isolated calcified popliteal artery lesions. Between January 2020 and December 2022, 62 patients with isolated atherosclerotic lesions of the popliteal artery underwent endovascular treatment by use of rotational atherectomy (Phoenix, Philips USA, (subgroup A) or Jetstream, Boston USA, (subgroup B), atherectomy systems) and additional balloon angioplasty in two vascular centers. The primary outcome measures were: 1. periprocedural clinical and technical success (<30% residual stenosis and no need for bailout stenting due to flow-limiting dissection) and 2. postprocedural increase in the ankle brachial index of more than 0.1. The overall rate of bailout stenting was 4.8%, whereas the procedural success rate was 98.4%. The rate of procedural complications included 3.7% and 5.7% peripheral embolizations in the subgroups A and B, respectively, and no vessel perforations were noted. All embolizations were successfully treated by catheter aspiration or capture in the pre-treatment placed filter system. In addition, 1 (3.7%) pseudoaneurysm in the groin was reported in subgroup A and treated by surgical means. Median ABI of the affected limbs improved from 0.55 (0.2) to 0.70 (0.2) in subgroup A and from 0.50 (0.2) to 0.95 (0.1) in subgroup B (DABI of 0.15 versus 0.45, p < 0.001). The combination of rotational atherectomy and balloon angioplasty in the popliteal artery showed reproducible outcomes in 2 centers, with low incidence of complications and low rates of bail-out stenting. These findings may contribute to more liberal use of such devices especially in segments with high risk for stent factures and occlusions.

РЕЗУЛЬТАТЫ РЕНТГЕНЭНДОВАСКУЛЯРНЫХ ВМЕШАТЕЛЬСТВ НА ИНФРАИНГВИНАЛЬНЫХ АРТЕРИЯХ ПРИ ХРОНИЧЕСКОЙ ИШЕМИИ НИЖНИХ КОНЕЧНОСТЕЙ АТЕРОСКЛЕРОТИЧЕСКОГО ГЕНЕЗА

Background. X-ray endovascular arterial interventions become the operation of choice for atherosclerotic lesions of the infrainguinal arteries. The purpose of the study. To perform a comprehensive retrospective analysis of the outcomes of infrainguinal balloon angioplasty and stenting in the treatment of chronic lower limb ischemia of atherosclerotic genesis, depending on the initial stage of lower extremities chronic arterial insufficiency, the age of patients, the type of infrainguinal artery lesion according to TASC II, the presence of diabetes mellitus. Material and methods. The study included 85 patients with chronic arterial insufficiency of the lower extremities who underwent X-ray endovascular interventions on the infrainguinal arteries in 2015. Results. By the end of the 7-year follow-up period, the lower limb in healthy patients was preserved in 50.6% cases, but this indicator among the patients who did not undergo repeated X-ray endovascular interventions and open arterial operations was 28.2%. The preservation of the lower limb in patients with lower extremities chronic arterial insufficiency at the initial 2b stage was 42.9%, at stage 3 – 30%, at stage 4 – 11.1%. In patients of the middle, elderly and senile age, X-ray endovascular surgery was effective in 23.1%, 24.4%, 41.2% cases. The effectiveness of endovascular interventions in patients with the TASC II A, B, C and D atherosclerotic artery lesions was 46.2%, 27.3%, 16.6%, 10.5%. After 7 years the lower limb was preserved in 7.7% and 31.9% of the patients with and without diabetes mellitus, the frequency of repeated X-ray endovascular interventions was 2.7% and 23.1%, and survival rate was 38.5% and 68.1% correspondingly. Conclusions. The outcomes of X-ray endovascular interventions in patients with infrainguinal arterial lesion depend on the stage of the lower extremities chronic arterial insufficiency, the age of patients, the TASC II type of the infrainguinal arteries damage, the presence of diabetes mellitus.

Potential miRNA biomarkers and therapeutic targets for early atherosclerotic lesions

Identification of potential therapeutic targets and biomarkers indicative of burden of early atherosclerosis that occur prior to advancement to life-threatening unstable plaques is the key to eradication of CAD prevalence and incidences. We challenged 16 baboons with a high cholesterol, high fat diet for 2 years and evaluated early-stage atherosclerotic lesions (fatty streaks, FS, and fibrous plaques, FP) in formalin-fixed common iliac arteries (CIA). We used small RNA sequencing to identify expressed miRNAs in CIA and in baseline blood samples of the same animals. We found 412 expressed miRNAs in CIA and 356 in blood samples. Eight miRNAs (miR-7975, -486-5p, -451a, -191-5p, -148a-3p, -17-5p, -378c, and -144-3p) were differentially expressed between paired fatty streak lesion and no-lesion sites of the tissue, and 27 miRNAs (e.g., miR-92a-3p, -5001, -342-3p, miR-28-3p, -21-5p, -221-3p, 146a-5p, and -16-5p) in fibrous plaques. The expression of 14 blood miRNAs significantly correlated with extent of lesions and the number of plaques. We identified coordinately regulated miRNA-gene networks in which miR-17-5p and miR-146a-5p are central hubs and miR-5001 and miR-7975 are potentially novel miRNAs associated with early atherosclerosis. In summary, we have identified miRNAs expressed in lesions and in blood that correlate with lesion burden and are potential therapeutic targets and biomarkers. These findings are a first step in elucidating miRNA regulated molecular mechanisms that underlie early atherosclerosis in a baboon model, enabling translation of our findings to humans.

The Joint Link of the rs1051730 and rs1902341 Polymorphisms and Cigarette Smoking to Peripheral Artery Disease and Atherosclerotic Lesions of Different Arterial Beds.

Genome-wide association studies (GWAS) have discovered numerous single nucleotide polymorphisms (SNP) contributing to peripheral artery disease (PAD), but their joint effects with risk factors like cigarette smoking (CS) on disease susceptibility have not been systematically investigated. The present study looked into whether CS mediates the effects of GWAS loci on the development of PAD and atherosclerotic lesions in different arterial beds. DNA samples from 1263 unrelated individuals of Slavic origin including 620 PAD patients and 643 healthy subjects were genotyped by the MassArray-4 system for rs1051730, rs10134584, rs1902341, rs10129758 which are known as PAD-associated GWAS loci. The rs1051730 polymorphism was strongly associated with an increased risk of PAD (p = 5.1 × 10-6), whereas rs1902341 did not show an association with disease risk. The rs1051730 polymorphism was associated with increased plasma levels of LDL cholesterol (p = 0.001), and conferred a greater risk of PAD in cigarette smokers than in nonsmokers (p < 0.01). Interestingly, the rs1902341T allele was associated with an increased risk of PAD in smokers and a decreased disease risk in nonsmokers. SNPs and CS were both linked to unilateral and/or bilateral atherosclerotic lesions of peripheral vessels, as well as the abdominal aorta, coronary, and cerebral arteries. The studied polymorphisms exert pleiotropic and cigarette smoking-mediated effects on atherosclerotic lesions of different arterial beds.

Mechanism of Buyang Huanwu Decoction glycosides against atherosclerotic inflammation through NF-κB signaling pathway

This study aims to explore the effect of Buyang Huanwu Decoction glycosides on the inflammatory response of apolipoprotein E~(-/-)(ApoE~(-/-)) mice and RAW264.7 cells through nuclear factor kappa-B(NF-κB) signaling pathway. In the in vivo experiment, ApoE~(-/-) mice were fed with high-fat diets for 12 weeks to induce the animal model of atherosclerosis, and 75 μg·mL~(-1) oxidized low-density lipoprotein(Ox-LDL) incubated RAW264.7 cells for 24 h to establish the atherosclerosis cell model. Automatic biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), Western blot, and droplet digital polymerase chain reaction(PCR) were used to determine the blood lipid levels, aortic intimal thickness, inflammatory factor content, NF-κB pathway-related proteins, and mRNA expression levels, and evaluate arterial atherosclerotic lesions and anti-atherosclerotic mechanisms of the drug. The model of atherosclerosis was successfully established in ApoE~(-/-) mice after 12 weeks of feeding with high-fat diets. In the model group, the plasma levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-C) were increased(P&lt;0.01), the intima of the blood vessels was thickened, the levels of inflammatory factors tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were increased, and the protein and mRNA expressions of NF-κB and inhibitor of NF-κB(IκBα) were significantly increased as compared with the control group. Compared with the model group, the high-dose Buyang Huanwu Decoction glycoside group decreased the plasma levels of TC, TG, and LDL-C, reduced the plaque area and thickness and the content of inflammatory factor TNF-α, and inhibited the protein and mRNA expressions of NF-κB and IκBα, with the effect same as Buyang Huanwu Decoction. In the in vivo experiment, 75 μg·mL~(-1) Ox-LDL stimulated RAW264.7 cells for 24 h to successfully establish a foam cell model. As compared with the control group, the nuclear amount of NF-κB and the protein and mRNA expressions of IκBα in the model group increased. Compared with the model group, the middle-dose and high-dose Buyang Huanwu Decoction glycoside groups decreased the nuclear amount of NF-κB and the protein and mRNA expressions of IκBα. The above results show that the glycosides are the main effective substances of Buyang Huanwu Decoction against atherosclerosis, which inhibit the NF-κB pathway and reduce the inflammatory response, thus playing the role against atherosclerotic inflammation same as Buyang Huanwu Decoction.

Clinical efficacy of a method for identifying patients at high risk of carotid atherosclerosis in rheumatoid arthritis

Objective: to test the patented “Method for determining a high risk of atherosclerosis in rheumatoid arthritis” on patients with rheumatoid arthritis.Materials and methods: 74 patients with RA who underwent inpatient treatment were examined. Gender composition of respondents: 77% women and 23% men. Mean age 54.1±9.1 years. The duration of RA is from 1 year to 26 years. 85.1% were diagnosed with a high degree of disease activity. Erosive arthritis was detected radiographically in 41 patients (55.4%). 83.7% (n=62) were seropositive for RF, 81% for ACCP (n=60). All received basic anti-inflammatory therapy. Systemic glucocorticoid therapy was received by 33.7%. All patients were calculated cardiovascular risk according to SCORЕ and mSCORЕ Also, all patients underwent duplex scanning of the BCA to detect atherosclerosis.Results: no significant increase in traditional factors of cardiovascular diseases was found among patients. When CVR was stratified according to SCORE, the frequency of low risk was 32.4%, moderate — 59.5%, high — 5.4%, very high — 2.7%. When using mSCORE, low risk was found in 27%, moderate — 56.7%, high — 13.5%, very high — 2.7%. Atherosclerotic plaques (ASP) in the carotid arteries in patients stratified according to SCORE for moderate, high and very high risk was detected in 68%, in persons with similar risks according to mSCORE — in 66.7%. With a score of 4 or more when using the tested method, ASP was found in 77.8%. Sensitivity for the detection of ASP in the carotid arteries using SCORE was 0.77, with mSCORE and the tested method 0.81 and 0.95, respectively. Specificity 0.47, 0.4 and 0.6 respectively. Positive predictive power for SCORE — 0.68, mSCORE — 0.67, tested method — 0.77. Negative predictive power for SCORE — 0.58, mSCORE — 0.6, tested method — 0.9.Conclusion: the study showed that our proposed method, which uses traditional clinical markers, significantly increases the sensitivity, specificity, and negative predictive power of calculation methods for identifying a group of individuals with a high risk of atherosclerotic lesions of extracranial arteries against the background of rheumatoid arthritis compared with using the SCORE and mSCORE parameters.

Application value of excimer laser ablation combined with drug-coated balloon in non-stent atherosclerotic lesions of lower extremity arteries

Objective: To examine the effect of excimer laser ablation (ELA) combining with drug-coated balloon (DCB) for atherosclerotic lesions in no-stenting zones (NSZ) of the lower extremity. Methods: From June 2019 to December 2021, 46 patients who underwent ELA combining with DCB in lesions of NSZ at Zhongshan Hospital, Fudan University and Jinshan Hospital, Fudan University were retrospectively enrolled, including 29 males and 17 females. The age was (72.5±11.7) years (range: 42 to 93 years). Among them, 44 lesions (95.7%, 44/46) were in popliteal artery and 2 lesions (4.3%, 2/46) were in common femoral artery. Chronic total occlusion (CTO) was observed in 31 patients (76.4%, 31/46), and stenotic lesions were observed in 15 patients (32.6%, 15/46). The length of lesions was (7.3±2.7) cm (range: 3.0 to 13.2 cm). Patients were followed at 6, 12 months after surgery and every year thereafter, and they underwent Doppler and CT angiography examination at each follow-up point. The primary endpoint was primary patency. The secondary endpoints included major amputation-free survival (MAFS) rate, technical success, bailout stent, ankle-brachial index (ABI), target lesion reintervention (TLR). Student t test was applied to compare the difference between ABI of 6 or 12 months after surgery and the baseline. Primary patency, freedom from TLR, and MAFS rate were calculated by Kaplan-Meier method. Results: The technical success rate was 91.3% (42/46). The rate of procedure-related complication was 6.5% (3/46), and all the complications were distal embolization. The rate of flow-limiting dissection was 8.7% (4/46). ABI was significantly increased at 6 and 12 months compared to preoperatively (0.90±0.10 vs. 0.42±0.10, t=-4.48, P<0.01; 0.87±0.12 vs. 0.42±0.10, t=-5.21, P<0.01). The follow-up time[M(IQR)] was 22.5 (8.8) months (range: 6 to 32 months). TLR was performed in 4 patients (4/46, 8.7%). The 2-year primary patency was 86.2% (95%CI: 71.8% to 93.5%). The 2-year freedom from TLR and MAFS rate were 90.7% (95%CI: 77.0% to 96.4%) and 97.8% (95%CI: 85.6% to 99.7%), respectively. Conclusion: ELA combining with DCB can be applied to treat atherosclerotic lesions in NSZ.

ATIC-Associated De Novo Purine Synthesis Is Critically Involved in Proliferative Arterial Disease.

Proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of arterial diseases, especially in arterial restenosis after angioplasty or stent placement. VSMCs reprogram their metabolism to meet the increased requirements of lipids, proteins, and nucleotides for their proliferation. De novo purine synthesis is one of critical pathways for nucleotide synthesis. However, its role in proliferation of VSMCs in these arterial diseases has not been defined. De novo purine synthesis in proliferative VSMCs was evaluated by liquid chromatography-tandem mass spectrometry. The expression of ATIC (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase), the critical bifunctional enzyme in the last 2 steps of the de novo purine synthesis pathway, was assessed in VSMCs of proliferative arterial neointima. Global and VSMC-specific knockout of Atic mice were generated and used for examining the role of ATIC-associated purine metabolism in the formation of arterial neointima and atherosclerotic lesions. In this study, we found that de novo purine synthesis was increased in proliferative VSMCs. Upregulated purine synthesis genes, including ATIC, were observed in the neointima of the injured vessels and atherosclerotic lesions both in mice and humans. Global or specific knockout of Atic in VSMCs inhibited cell proliferation, attenuating the arterial neointima in models of mouse atherosclerosis and arterial restenosis. These results reveal that de novo purine synthesis plays an important role in VSMC proliferation in arterial disease. These findings suggest that targeting ATIC is a promising therapeutic approach to combat arterial diseases.

The C1q-ApoE complex: A new hallmark pathology of viral hepatitis and nonalcoholic fatty liver disease.

We recently identified a high-affinity C1q-ApoE complex in human artery atherosclerotic intima lesions and in human amyloid plaques of Alzheimer’s Disease brains defining a common pathogenetic pathway of two diverse diseases, i.e. atherosclerosis and dementia. C1q is the initiating and controlling protein of the classical complement cascade (CCC), which occupies a key role in multiple acute and chronic inflammatory tissue responses. C1q is largely produced by myeloid cells including Kupffer cells (KCs) and subsequently secreted into the circulation as an inactive preprotein. Its binding partner, Apolipoprotein E (ApoE), is produced by KCs and hepatocytes and it is also secreted into the circulation, where it regulates essential steps of lipid transport. In addition to its major source, ApoE can be produced by non-liver cells including immune cells and multiple other cells depending on local tissue contexts. To initiate the CCC cascade, C1q must be activated by molecules as varied as oxidized lipids, amyloid fibrils, and immune complexes. However, ApoE is mute towards inactive C1q but binds at high-affinity to its activated form. Specifically, our studies revealed that ApoE is a CCC-specific checkpoint inhibitor via the formation of the C1q-ApoE complex. We proposed that it may arise in multiple if not all CCC-associated diseases and that its presence indicates ongoing CCC activity. Here, we turned to the liver to examine C1q-ApoE complexes in human B- and C-viral hepatitis and nonalcoholic fatty liver disease (NAFLD). In addition, we used multidrug-resistance-2 gene-knockout (Mdr2-KO) mice as a model for inflammatory liver disease and hepatocellular carcinoma (HCC) pathogenesis. In normal murine and human livers, KCs were the major C1q-producing cell type while hepatocytes were the primary ApoE-forming cell type though the C1q-ApoE complex was rare or nonexistent. However, significant numbers of C1q-ApoE complexes formed in both Mdr2-KO, human viral hepatitis, and NAFLD around portal triads where immune cells had infiltrated the liver. Additionally, high numbers of C1q-ApoE complexes emerged in human livers in areas of extracellular lipid droplets across the entire liver parenchyma in NAFLD-affected patients. Thus, the C1q-ApoE complex is a new pathological hallmark of viral hepatitis B and C and NAFLD.

Pure Endovascular versus Hybrid Approach for Management of Iliofemoral Arterial Disease: A Randomized Controlled Trial.

Common femoral artery (CFA) atherosclerotic lesions currently remain one of the last limitations for adoption of endovascular repair as the first-line treatment, easy surgical accessibility, and, last but not least, favorable long-term outcomes, still making CFA disease treatment part of the surgical domain. In the last 5 years, improvement of the endovascular equipment and technical skills of the operators have led to an increase in percutaneous CFA procedures. A single-center randomized prospective study of 36 symptomatic (Rutherford 2-4) CFA stenotic or occlusive lesions were included, and patients were randomized over two groups based on the management approach SUPERA versus hybrid technique. Patients had a mean age 60.8 ± 8.2 years. Thirty-two (88.9%) patients reported improvement of the clinical symptoms, 28 (87.5%) patients had intact pulse postoperatively, and 28 (87.5%) had patent vessels. Follow-up showed that none developed reocclusion or restenosis during the period of follow-up. Comparison of difference in peak systolic velocity ratio (PSVR) among study groups showed that the hybrid technique had more reduction of PSVR postintervention compared to the SUPERA group with a p -value of < 0.0001. Safety and feasibility of endovascular approach with the SUPERA stent to the CFA (no stent zone) has low incidence of postoperative morbidity and mortality in well experienced surgical hands.

Application of Model-Building Based on Arterial Ultrasound Imaging Evaluation to Predict CHD Risk.

Objective Atherosclerotic is a chronic systemic disease that may occur in multiple vascular beds, including the carotid arteries, renal arteries, lower limb arteries, and cerebral vessels. Coronary atherosclerosis shares similar risk factors, pathogenesis, and pathophysiological basis with the atherosclerotic lesions of arteries at these sites. Arterial ultrasound assessment data were used to explore the correlation of atherosclerotic disease with CHD lesions and their severity and the number of lesion branches, as well as to evaluate its value in predicting CHD risk, in combination with traditional risk factors. Methods A total of 363 inpatients with suspected CHD in the Department of Cardiology of the First Hospital of Harbin Medical University from November 2017 to June 2021 were selected. Patient clinical data, blood biochemical examination results, and ultrasound examination of neck vessels, abdominal arteries, and limb arteries were collected to obtain atherosclerosis assessment data. We then compared the differences between the CHD group and the control group, analyzed their correlation with CHD lesions and severity and the number of lesion branches, and evaluated the correlation with the coronary Gensini score. After adjustment for traditional risk factors, logistic regression was applied to analyze the relationship between arterial ultrasound assessment data and the risk of CHD. In addition, ROC plots were drawn to evaluate the risk of arterial ultrasound assessment data, combined with traditional risk factors, to predict CHD. Results With regard to abnormal blood biochemical index values, differences in lipids, HDL-C, FIB, CK-MB, hs-cTnI, BNP, and GGT were found between the CHD group and the control group. Carotid plaque count, abdominal aortic flow velocity, inferior mesenteric artery flow velocity, classification of the number of stenotic branches of abdominal aortic branch arteries, lower-extremity-artery plaque count, degree of lower-extremity-artery stenosis, and lower-extremity-artery AS were risk factors for arterial ultrasound assessment data of CHD. Carotid plaque count, carotid artery AS, inferior mesenteric artery flow velocity, abdominal aortic flow velocity, abdominal aortic plaque count, abdominal aortic branch artery stenosis branch classification, lower-extremity-artery plaque count, lower-extremity-artery stenosis branch classification, degree of lower-extremity-artery stenosis, and lower-extremity-artery AS, combined with traditional risk factors, were mostly more effective than traditional risk factor models in predicting CHD, its severity, and the number of branch lesions; moreover, the predictive value was higher. Specifically, carotid plaque count, carotid AS, lower-extremity-artery AS, the degree of stenosis of lower-extremity arteries, and abdominal aortic branch artery stenosis branch classification can be used as predictor variables for CHD risk. Among these variables, the carotid plaque count can be used as an independent predictor of CHD. Conclusion The incidence of arterial intima–media thickening (IMT), plaques, and stenosis can provide a reference for understanding the pattern of systemic atherogenesis and the distribution of atherosclerosis.

Contrast enhanced magnetic resonance imaging in early assessment of atherosclerotic lesion of abdominal aortic wall and common iliac arteries

Highlights. Early atherosclerotic changes in the abdominal aortic wall and common iliac arteries in patients without clinical manifestations of critical atherosclerotic stenosis of the lower extremity arteries were studied using contrast enhanced magnetic resonance imaging. A method for quantitative characterization of the accumulation of paramagnetic contrast in the abdominal aortic wall and common iliac arteries is presented.Aim. To study the pattern of early atherosclerotic lesions of the abdominal aortic wall and common iliac arteries in patients without clinical manifestations of critical atherosclerotic stenosis of the lower extremity arteries using paramagnetic contrast enhancement (CE-) MRI.Methods. The retrospective study included 36 patients (25 men, 11 women) who underwent MRI of the lumbar spine with CE, without signs of atherosclerosis of the lower extremities. Subsequently, 2.5 and 4 years after CE-MRI, two patients developed acute leg ischemia and required vascular surgeries. At the time of the study, both had higher levels of C-reactive protein in the blood (6.3 mg/L and 5.9 mg/L, while the other patients had &lt;4.2 mg/L). MRI included T2 – and T1-weighted spin-echo scans (T2-w and T1-w) in the axial and sagittal planes, before and in 10-15 minutes after contrast injection. The index of enhancement (IE) of T1-w was calculated based on the ratio of mean intensities of the region of arterial wall over aorta and iliac arteries in CE-MRI and pre-contrast MRI: IE = Int.T1–w. CE / Int. T1–w pre-contrast.Results. Depending on the IE of the abdominal aortic wall in CE-MRI, patients were divided into three groups: group 1 (n = 11) with IE ≤1.05; group 2 (n = 16) with 1.05 &lt;IE ≤1.15; group 3 (n = 9) with IE &gt;1.15. The aortic IE in all three groups was 1,03 (1,01;1,03); 1,10 (1,09;1,15); 1,36 (1,16;1,40) respectively (p&lt;0.001). The thickness of the abdominal aortic wall progressively increased moving up the group 1, while statistically significant differences were found only between the groups 1 and 3, and the groups 2 and 3 (p&lt;0.001). There were no differences in the wall thickness of the common iliac arteries and the diameter of all vessels studied between the groups. Two patients from the group 3 later presented with acute limb ischemia.Conclusion. The state of the abdominal aortic wall and common iliac arteries should be evaluated, and IE of T1-w should be calculated when performing CE-MRI examination of the area of the descending aorta to assess pathological neoangiogenesis as the most important component of atherogenesis.