Abdominal Aortic Atherosclerosis Research Articles

Radiation-induced Renal Artery Stenosis

We present a case of a 33 year old male presenting with uncontrolled hypertension, requiring four drugs and renal dysfunction. Investigations revealed calcific atherosclerosis of abdominal aorta and bilateral renal artery stenosis. He had received radiotherapy for abdominal Non-Hodgkin’s lymphoma 14 years ago. Transluminal angioplasty was done on the right side resulting in improved renal function and normalization of blood pressure. Radiotherapy for intra-abdominal malignancy induces atherosclerosis process in arteries within field of irradiation and they manifest after many years of the initial insult.

Targeting aging and age-related diseases with vaccines.

Aging is a major risk factor for numerous chronic diseases. Vaccination offers a promising strategy to combat these age-related diseases by targeting specific antigens and inducing immune responses. Here, we provide a comprehensive overview of recent advances in vaccine-based interventions targeting these diseases, including Alzheimer's disease, type II diabetes, hypertension, abdominal aortic aneurysm, atherosclerosis, osteoarthritis, fibrosis and cancer, summarizing current approaches for identifying disease-associated antigens and inducing immune responses against these targets. Further, we reflect on the recent development of vaccines targeting senescent cells, as a strategy for more broadly targeting underlying causes of aging and associated pathologies. In addition to highlighting recent progress in these areas, we discuss important next steps to advance the therapeutic potential of these vaccines, including improving and robustly demonstrating efficacy in human clinical trials, as well as rigorously evaluating the safety and long-term effects of these vaccine strategies.

Identification of key genes for atherosclerosis in different arterial beds

Atherosclerosis (AS) is the pathologic basis of various cardiovascular and cerebrovascular events, with a high degree of heterogeneity among different arterial beds. However, mechanistic differences between arterial beds remain unexplored. The aim of this study was to explore key genes and potential mechanistic differences between AS in different arterial beds through bioinformatics analysis. Carotid atherosclerosis (CAS), femoral atherosclerosis (FAS), infrapopliteal atherosclerosis (IPAS), abdominal aortic atherosclerosis (AAS), and AS-specific differentially expressed genes (DEGs) were screened from the GSE100927 and GSE57691 datasets. Immune infiltration analysis was used to identify AS immune cell infiltration differences. Unsupervised cluster analysis of AS samples from different regions based on macrophage polarization gene expression profiles. Weighted gene co-expression network analysis (WGCNA) was performed to identify the most relevant module genes with AS. Hub genes were then screened by LASSO regression, SVM-REF, and single-gene differential analysis, and a nomogram was constructed to predict the risk of AS development. The results showed that differential expression analysis identified 5, 4, 121, and 62 CAS, FAS, IPAS, AAS-specific DEGs, and 42 AS-common DEGs, respectively. Immune infiltration analysis demonstrated that the degree of macrophage and mast cell enrichment differed significantly in different regions of AS. The CAS, FAS, IPAS, and AAS could be distinguished into two different biologically functional and stable molecular clusters based on macrophage polarization gene expression profiles, especially for cardiomyopathy and glycolipid metabolic processes. Hub genes for 6 AS (ADAP2, CSF3R, FABP5, ITGAX, MYOC, and SPP1), 4 IPAS (CLECL1, DIO2, F2RL2, and GUCY1A2), and 3 AAS (RPL21, RPL26, and RPL10A) were obtained based on module gene, gender stratification, machine learning algorithms, and single-gene difference analysis, respectively, and these genes were effective in differentiating between different regions of AS. This study demonstrates that there are similarities and heterogeneities in the pathogenesis of AS between different arterial beds.

Antioxidants and azd0156 Rescue Inflammatory Response in Autophagy-Impaired Macrophages.

Autophagy is a lysosomal degradation system that eliminates and recycles damaged intracellular organelles and proteins. Inflammatory macrophages play a critical role in the development of various age-related inflammatory illnesses such as abdominal aortic aneurysm, atherosclerosis, and rheumatoid arthritis; therefore, identifying the mechanisms that cause macrophage inflammation is crucial for a better understanding of and developing therapeutics for inflammatory diseases. Previous research has linked autophagy to macrophage inflammation; Atg16L1-deficient macrophages increase IL-1 and IL-18 production via inflammasome activation. In this study, however, we show an alternative pathway of macrophage inflammation in an autophagy-deficient environment. We found that inhibiting autophagy in THP1 macrophages progressively increased the expression of p65-mediated inflammatory genes. This effect was reversed by treatment with antioxidants or azd0156, an ataxia telangiectasia mutated (ATM) inhibitor. In addition, our results showed that M1 macrophages inhibit autophagy and induce DNA damage, whereas M2 macrophages activate autophagy and reduce DNA damage. Importantly, the chemical activation of autophagy or ATM inhibition during M1 polarization reduced the M1 phenotype and inflammation, whereas inhibiting autophagy during M2 polarization also reduced the M2 phenotype. Thus, our findings highlight the importance of the autophagy-ATM pathway in driving macrophage inflammation.

Structural features of the Achilles tendon in men with dyslipidemia and atherosclerosis

Highlights. A large number of studies are devoted to changes in connective tissues in persons with familial hypercholesterolemia. Studies that are focused on these changes in patients with dyslipidemia without family history of dyslipidemia are few, and most of them are based on ultrasound methods. The data presented in the article make it possible to timely assess the presence of minor changes in the Achilles tendons and thereby obtain additional information about the mechanism of lipid deposition in various tissues.Aim. To determine structural features of the Achilles tendon in men with dyslipidemia and atherosclerosis.Methods. The study included 138 men aged 45–65 years with or without atherosclerosis of the common carotid artery or the abdominal aorta and their aortic branches verified by multislice computed tomography.Results. In individuals with atherosclerosis, the frequency of calcification of the Achilles tendon was 2.5 times higher than in individuals without atherosclerosis. In individuals with carotid artery atherosclerosis, the cross-sectional area of the Achilles tendon was 1.2 times larger than in individuals with abdominal aortic atherosclerosis. In individuals with carotid artery atherosclerosis, the density of the Achilles tendon was 1.1 times higher than in individuals with abdominal aortic atherosclerosis. In individuals with carotid artery atherosclerosis, the frequency of calcification of the Achilles tendon was 2.0 times higher than in individuals with abdominal aortic atherosclerosis. An increase in the cross-sectional area of the tendon and its density, regardless of other factors, including the localization of the atherosclerosis, is directly associated with the total blood cholesterol. The presence of lipid and calcium deposition in the tendons, regardless of other factors, is directly associated with the total blood cholesterol and some of its fractions. The presence of lipid deposition in the tendons is inversely associated with the level of level of phosphate in the blood. The thickening of the tendon and the increase in its density is directly associated with the age of men.Conclusion. The study results revealed that persons with dyslipidemia and atherosclerosis present with changes in the connective tissues – in the structure of tendons, regardless of family history.

Scale down and optimized automated production of [68Ga]68Ga-DOTA-ECL1i PET tracer targeting CCR2 expression

BackgroundRecently it has been identified a short peptide that showed allosteric antagonism against C–C motif chemokine receptor 2 (CCR2) expressed on inflammatory monocyte and macrophages. A 7-d-amino acid peptidic CCR2 inhibitor called extracellular loop 1 inverso (ECL1i), d(LGTFLKC) has been identified and labeled to obtain a new probe for positron emission tomography in pulmonary fibrosis, heart injury, abdominal aortic aneurysm inflammation, atherosclerosis, head and neck cancer. Our goal was to develop, optimize and validate an automated synthesis method for [68Ga]68Ga-DOTA-ECL1i to make it available for a broader community. The synthesis of [68Ga]68Ga-DOTA-ECL1i was done using the Scintomics GRP® module with the already estabilished synthesis template for [68Ga]68Ga-DOTATOC/[68Ga]68Ga-PSMA. The radiopharmaceutical production was optimized scaling down the amount of DOTA-ECL1i (from 50 to 10 μg), evaluating synthesis efficiency and relevant quality control parameters in accordance with the European Pharmacopeia.ResultsBest results were yielded with 20 μg DOTA-ECL1i and then the process validation was carried out by producing three different batches on three different days obtaining an optimal radiochemical yield (66.69%) as well as radiochemical purity (100%) and molar activity (45.41 GBq/µmol).Conclusions[68Ga]68Ga-DOTA-ECL1i was successfully synthesized and it is, thus, available for multi-dose application in clinical settings.

Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens.

Inflammatory dysregulation of mechanosensitive developmental genes may be central to atherogenesis. In the present seven-week model, we utilized colchicine regimens to curtail aortic atherogenesis in New Zealand White rabbits. We also explored the effect of colchicine regimens on atheroprotective (<i>Klotho</i>, <i>HOXA5</i>, <i>NOTCH1</i>, and <i>OCT4</i>) and proatherogenic (<i>HIF1a</i>, <i>SOX2</i>, <i>BMP4</i>, and <i>NANOG</i>) genes. The control (n = 6) and group A (n = 6) received standard and cholesterol-enriched chow, respectively. Groups B (n = 8) and C (n = 8) were fed hypercholesterolemic diet and were treated with colchicine plus fenofibrate or N-acetylcysteine (NAC), respectively. Group A developed significantly greater thoracic and abdominal aortic atherosclerosis compared to groups B (<i>p</i> &lt; 0.001) and C (<i>p</i> &lt; 0.001). Combining colchicine with NAC resulted in stronger atheroprotection both in the thoracic and the abdominal aorta. In group A thoracic aortas, <i>Klotho</i> was downregulated compared to controls (95% CI: 1.82-15.76). Both colchicine regimens upregulated <i>Klotho</i> back to baseline levels (<i>p</i> &lt; 0.001). Colchicine/fenofibrate also significantly upregulated thoracic <i>NOTCH1</i> compared to controls (95% CI: -8.09 to -0.48). Colchicine/NAC significantly reduced thoracic <i>NANOG</i> expression compared to hyperlipidemic diet alone (95% CI: 0.37-8.29). In the abdominal aorta, hypercholesterolemic diet resulted in significant downregulation of <i>HOXA5</i> (95% CI: 0.03-2.74) which was reversed with colchicine/NAC back to baseline (95% CI: -1.19 to 1.51). Colchicine/fenofibrate downregulated <i>HIF1a</i> compared to baseline (95% CI: 0.83-6.44). No significant differences were noted in terms of <i>BMP4</i>, <i>SOX2</i>, and <i>OCT4</i>. Overall, the aortic expression pattern of mechanosensitive genes seems to be spatially influenced by a hyperlipidemic diet and can be modified using colchicine-based therapy.

The aortic expression pattern of mechanosensitive stem cell genes is spatially deranged by western-type diet but can be regulated with colchicine-based anti-inflammatory treatment

Abstract Background Inflammatory dysregulation of mechanosensitive stem cell genes may be central to atherogenesis. Purpose In the present animal model, we utilized colchicine-based regimens to curtail the development of thoracic and abdominal aortic atheromatosis. We also explored the effect of anti-inflammatory therapy on atheroprotective (Klotho, HOXA5, NOTCH1, OCT4) and proatherogenic (HIF1a, SOX2, BMP4, NANOG) genes. Methods Twenty-eight New Zealand White rabbits were divided to four groups. The control group (n=6) was fed standard chow, group A (n=6) was fed chow enriched with 1% w/w cholesterol, group B (n=8) was fed the same cholesterol-enriched diet plus 2 mg/kg body weight/day colchicine and 250 mg/kg body weight/day fenofibrate, while group C (n=8) was fed the same diet plus 2 mg/kg body weight/day colchicine and 15 mg/kg body weight/day N-acetylcysteine (NAC). After seven weeks, all animals were euthanized, and their aortas were resected. Atherosclerotic plaque area was estimated via morphometric analysis. Gene expression was quantified with qRT-PCR. Results Group A developed significantly more extensive thoracic and abdominal aortic atherosclerosis compared to groups B (p&amp;lt;0.001) and C (p&amp;lt;0.001). Combining colchicine with NAC instead of fibrate resulted in stronger atheroprotection both in the thoracic (MD: 6.6, 95% CI: 0.9–12.3) and the abdominal aorta (MD: 11.1, 95% CI: 6.0–16.3). In group A thoracic aortas, Klotho was downregulated compared to controls (MD: 8.79, 95% CI: 1.82–15.76). Both colchicine regimens upregulated Klotho back to baseline levels (p&amp;lt;0.001). Colchicine/fenofibrate also significantly upregulated thoracic NOTCH1 compared to controls (MD: −4.29, 95% CI: −8.09 to −0.48). Colchicine/NAC significantly reduced thoracic NANOG expression compared to hyperlipidemic diet alone (MD: 4.33, 95% CI: 0.37–8.29). In the abdominal aorta, cholesterol-enriched diet alone resulted in significant downregulation of HOXA5 (MD: 1.39, 95% CI: 0.03–2.74) which was reversed with colchicine/NAC back to baseline levels (MD: 0.16, 95% CI: −1.19 to 1.51). On the other hand, colchicine/fenofibrate downregulated HIF1a compared to baseline (MD: 3.64, 0.83–6.44). No statistically significant differences were noted in terms of BMP4, SOX2, and OCT4 expression in thoracic and abdominal aortic specimens. Conclusions The aortic expression pattern of mechanosensitive stem cell genes is spatially influenced by western-type diet and can be modified using anti-inflammatory regimens. In our experiment, hyperlipidemic diet drove thoracic and abdominal aortic atheromatosis by downregulating Klotho and HOXA5, respectively. Both colchicine regimens curtailed thoracic atheromatosis via upregulating Klotho. In the thoracic aorta, combining colchicine with fenofibrate also increased NOTCH1, while the addition of NAC reduced NANOG. In the abdominal aorta, combining colchicine with fenofibrate reduced HIF1a, whereas the addition of NAC upregulated HOXA5. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This research was funded by the Hellenic Surgical Society and the Hellenic Atherosclerosis Society.

The Nonproteolytic Intracellular Domain of Membrane-Type 1 Matrix Metalloproteinase Coordinately Modulates Abdominal Aortic Aneurysm and Atherosclerosis in Mice-Brief Report.

MT1-MMP (membrane-type 1 matrix metalloproteinase, MMP-14) is a transmembrane-anchored protein with an extracellular proteinase domain and a cytoplasmic tail devoid of proteolytic functions but capable of mediating intracellular signaling that regulates tissue homeostasis. MT1-MMP extracellular proteolytic activity has been shown to regulate pathological remodeling in aortic aneurysm and atherosclerosis. However, the role of the nonproteolytic intracellular domain of MT1-MMP in vascular remodeling in abdominal aortic aneurysms (AAA) is unknown. We generated a mutant mouse that harbors a point mutation (Y573D) in the MT1-MMP cytoplasmic domain that abrogates the MT1-MMP signaling function without affecting its proteolytic activity. These mice and their control wild-type littermates were subjected to experimental AAA modeled by angiotensin II infusion combined with PCSK9 (proprotein convertase subtilisin/kexin type 9) overexpression and high-cholesterol feeding. The mutant mice developed more severe AAA than the control mice, with concomitant generation of intraaneurysmal atherosclerotic lesions and dramatically increased macrophage infiltration and elastin degradation. Aortic lesion-associated and bone marrow-derived macrophages from the mutant mice exhibited an enhanced inflammatory state and expressed elevated levels of proinflammatory Netrin-1, a protein previously demonstrated to promote both atherosclerosis and AAA. Our findings show that the cytoplasmic domain of MT1-MMP safeguards from AAA and atherosclerotic plaque development through a proteolysis-independent signaling mechanism associated with Netrin-1 expression. This unexpected function of MT1-MMP unveils a novel mechanism of synchronous onset of AAA and atherogenesis and highlights its importance in the control of vascular wall homeostasis.

Ultrasonographic Assessment of Atherosclerotic Renal Artery Stenosis in Elderly Patients with Chronic Kidney Disease: An Italian Cohort Study.

Although atherosclerotic renal artery stenosis (ARAS) is strictly associated with high cardiovascular risk and mortality, it often may remain unrecognized being clinically silent and frequently masked by co-morbidities especially in elderly patients with coexisting chronic kidney disease (CKD). The present observational study was conducted in elderly CKD-patients with atherosclerosis on other arterial beds. The aims were assessment of (1) ARAS prevalence; (2) best predictor(s) of ARAS, using duplex ultrasound; and (3) cardiovascular and renal outcomes at one-year follow-up. The cohort was represented by 607 consecutive in-patients. Inclusion criteria were age ≥65 years; CKD stages 2–5 not on dialysis; single or multiple atherosclerotic plaque on epiaortic vessels, abdominal aorta, aortic arch, coronary arteries, peripheral arteries that had been previously ascertained by one or more procedures. Duplex ultrasound was used to detect ARAS. Multiple regression analysis and ROS curve were performed to identify the predictors of ARAS. ARAS was found in 53 (44%) out of 120 patients who met the inclusion criteria. In univariate analysis, GFR (b = −0.021; p = 0.02); hemoglobin (b = −0.233; p = 0.02); BMI (b = 0.134; p = 0.036) and atherosclerosis of abdominal aorta and/or peripheral vessels (b = 1.025; p < 0.001) were associated with ARAS. In multivariable analysis, abdominal aorta and/or peripheral atherosclerosis was a significant (p = 0.002) predictor of ARAS. The area under the ROC curve was 0.655 (C.I. = 0.532–0.777; p = 0.019). ARAS is common in older CKD patients with extra-renal atherosclerosis, with the highest prevalence in those with aortic and peripheral atherosclerosis. ARAS may pass by unnoticed in everyday clinical practice.

Role of Sclerostin in Cardiovascular Disease.

Sclerostin is most recognized for its role in controlling bone formation but is also expressed in the heart, aorta, coronary, and peripheral arteries. This review summarizes research on sclerostin's role in cardiovascular disease. Rodent studies have found sclerostin to be expressed at sites of arterial calcification. In contrast, aortic sclerostin was reported to be downregulated in a mouse model of abdominal aortic aneurysm, and transgenic upregulation or administration of sclerostin was found to prevent abdominal aortic aneurysm and atherosclerosis formation. Sclerostin deficiency was reported to stimulate cardiac rupture in one rodent model. In humans, 7 of 11 studies reported a significant association between high serum sclerostin and high carotid intima media thickness. Ten of 15 studies reported a significant association between high serum sclerostin and severe arterial calcification. Twelve of 14 studies reported a significant association between high serum sclerostin and high arterial stiffness or atherosclerosis severity. Four of 9 studies reported a significant association between high serum sclerostin and high risk of cardiovascular events. A meta-analysis of randomized controlled trials suggested that administration of the sclerostin blocking antibody romosozumab did not significantly increase the risk of major adverse cardiovascular events (risk ratio, 1.14 [95% CI, 0.83-1.57]; P=0.54) or cardiovascular death (risk ratio, 0.92 [95% CI, 0.53-1.59]; P=0.71). Human genetic studies reported variants predisposing to low arterial sclerostin expression were associated with a high risk of cardiovascular events. Overall, past research suggests a cardiovascular protective role of sclerostin but findings have been inconsistent, possibly due to variations in study design, the unique populations and models studied, and the heterogeneous methods used.

Lipid-lowering treatment in a rabbit model of atherosclerosis: a vessel wall magnetic resonance imaging study.

BackgroundVessel wall magnetic resonance imaging (VWMRI) is currently one of the best imaging techniques for the non-invasive evaluation of intracranial atherosclerotic lesions. However, it is still impossible to obtain pathological specimens of intracranial atherosclerotic plaques in vivo. The establishment of experimental animal models of atherosclerotic lesions similar to those of humans could solve this deficiency.MethodsA model of abdominal aortic atherosclerosis in New Zealand white rabbits was established using abdominal aortic balloon dilatation combined with high-fat fodder. The pathological results were used as the reference standard for the successful establishment of the animal model. The rabbits with abdominal aortic atherosclerosis were randomly divided into the lipid-lowering treatment and the normal-fodder control groups. VWMRI and blood biochemical examinations were performed at 4, 12, and 24 weeks, and the radiologic-pathologic correlations were established.ResultsA rabbit abdominal aortic atherosclerosis model was established using balloon dilatation followed by high-fat fodder for 8 weeks. The lipid-lowering treatment reduced the plaque lipid core volume and decreased the plaque burden. However, it did not change plaque distribution, shape, or reverse vascular remodeling. Our pathological findings suggest that the lipid-lowering treatment reduced intraplaque macrophages but did not alter microvascular density.ConclusionsVWMRI accurately assessed the morphological changes of the plaques before and after the lipid-lowering treatment, and the results support the pathology results. VWMRI could be useful in experimental studies on the pathogenesis, diagnosis, and treatment of atherosclerotic lesions.

Assessing serum levels of SM22α as a new biomarker for patients with aortic aneurysm/dissection.

BackgroundAortic aneurysm/dissection (AAD) is now encountered more often because of the increasing prevalence of atherosclerosis and hypertension in the population. Despite many therapeutic improvements, in particular timely and successful surgery, in-hospital mortality rates are still higher. Timely identification of patients at high risk will help improve the overall prognosis of AAD. Since early clinical and radiological signs are nonspecific, there is an urgent need for accurate biomarkers. Smooth muscle 22α (SM22α) is a potential marker for AAD because of its abundant expression in vascular smooth muscle, which is involved in development of AAD.MethodsWe prepared three different mouse models, including abdominal aortic aneurysm, neointimal hyperplasia and atherosclerosis. SM22α levels were assessed in serum and vascular tissue of the mice. Next, the relationships between serum SM22α level and vascular lesion were studied in mice. Finally, serum from 41 patients with AAD, 107 carotid artery stenosis (CAS) patients and 40 healthy volunteers were tested for SM22α. Serum levels of SM22α were measured using an enzyme-linked immunosorbent assay (ELISA).ResultsCompared with the controls, serum SM22α levels were reduced in the models of aortic aneurysm, neointimal formation and atherosclerosis, and elevated in mice with ruptured aneurysm. Serum SM22α level was negatively correlated with apoptosis rate of vascular smooth muscle cells (VSMC), ratio of intima/ media (I/M) area and plaque size. Patients with AAD had significantly higher serum SM22α levels than patients with only CAS, or normal controls.ConclusionSerum SM22α could be a potential predictive marker for AAD, and regulation of VSMC is a possible mechanism for the effects of SM22α.

A regulator of G protein signaling 5 marked subpopulation of vascular smooth muscle cells is lost during vascular disease.

Vascular smooth muscle cell (VSMC) subpopulations relevant to vascular disease and injury repair have been depicted in healthy vessels and atherosclerosis profiles. However, whether VSMC subpopulation associated with vascular homeostasis exists in the healthy artery and how are their nature and fate in vascular remodeling remains elusive. Here, using single-cell RNA-sequencing (scRNA-seq) to detect VSMC functional heterogeneity in an unbiased manner, we showed that VSMC subpopulations in healthy artery presented transcriptome diversity and that there was significant heterogeneity in differentiation state and development within each subpopulation. Notably, we detected an independent subpopulation of VSMCs that highly expressed regulator of G protein signaling 5 (RGS5), upregulated the genes associated with inhibition of cell proliferation and construction of cytoskeleton compared with the general subpopulation, and mainly enriched in descending aorta. Additionally, the proportion of RGS5high VSMCs was markedly decreased or almost disappeared in the vascular tissues of neointimal formation, abdominal aortic aneurysm and atherosclerosis. Specific spatiotemporal characterization of RGS5high VSMC subpopulation suggested that this subpopulation was implicated in vascular homeostasis. Together, our analyses identify homeostasis-relevant transcriptional signatures of VSMC subpopulations in healthy artery, which may explain the regional vascular resistance to atherosclerosis at some extent.

Investigation of Relation between Abdominal Aortic Calcium Score and Renal Stone via Multislice Computed Tomography

Objective: The present study aimed to investigate the relation between abdominal aorta calcium score and renal stones (RS) using computed tomography (CT).&#x0D; Methods: This study comprised 352 subjects who underwent CT of urinary system in our clinic. One hundred and seventy-six subjects with RS were assigned to Group 1 and 176 subjects without RS were assigned to Group 2 (control group). The likely relation of calcium score, an indicator of atherosclerosis of abdominal aorta, with renal stone formation and stone volume, which has not been investigated previously, was investigated using multislice CT (MSCT).&#x0D; Results: Age distribution of the study subjects ranged from 19 years to 87 years (mean, 44.3±15.1 years). Of the study subjects, 224 (63.6%) were male and 128 (36.4%) were female. According to Agatston scoring, the mean aortic calcium score was 348.7±665.7 Agatston unit (AU) in Group 1 and 212.2±486.9 AU in Group 2. Stone volume was 38.1±25.7 cubic millimeter (mm3) in Group 1.&#x0D; Conclusions: Independently from RS volume, the frequency of abdominal aortic atherosclerosis was observed to be higher in the some aged patients with urolithiasis than in the normal subjects. The result was significant (p

Soluble Fms-like tyrosine kinase-1 (sFlt-1) is associated with subclinical and clinical atherosclerotic cardiovascular disease: The Dallas Heart Study

Background and aimsSoluble Fms-like tyrosine kinase-1 (sFlt-1) plays a role in angiogenesis, atherogenesis, and preeclampsia. The relationship of sFlt-1 with markers of subclinical atherosclerosis and future atherosclerotic cardiovascular disease (ASCVD) events in a generally healthy population is unknown. MethodsParticipants in the Dallas Heart Study with sFlt-1 measured were included (n = 3292). Abdominal aortic atherosclerosis was measured by MRI and coronary artery calcium (CAC) by CT. The cohort was also followed for subsequent ASCVD events (CV death, MI, stroke, unstable angina, revascularization). Multivariable linear and logistic regression analyses and Cox regression analyses were performed adjusting for demographics and traditional cardiac risk factors. ResultssFlt-1 levels were higher in older individuals, males, and African Americans, and tracked with most traditional risk factors. sFlt-1 was significantly associated with higher prevalence of aortic plaque [OR 1.33 (95% CI 1.02–1.73)], greater abdominal aortic wall thickness (p<0.01) and aortic plaque area (p<0.02) but no difference in coronary artery calcification. There were 322 ASCVD events over 12 years of follow-up. Higher sFlt-1 levels associated with increased ASCVD events in unadjusted (16.1% vs. 8.9%, p<0.001, quartile 4 vs. quartile 1) and adjusted analyses (HR 1.58 [1.14–2.18], p<0.01, quartile 4 vs. quartile 1). Findings were unchanged when analyzing sFlt-1 as a continuous variable or when excluding those with a history of ASCVD. ConclusionsIn a population-based cohort, sFlt-1 is associated with measures of subclinical aortic atherosclerosis and clinical ASCVD events. Future studies are warranted on the therapeutic potential of targeting sFlt-1 for atherosclerotic disease.

Reconstruction of infrarenal abdominal aortic occlusion using the Culotte stenting technique: a case report

Patients with clinically significant infrarenal abdominal aortic atherosclerosis are often encountered in the clinical practice of vascular and endovascular surgeons. In the absence of timely treatment, the ability to work and life quality of patients are sharply reduced, and in some cases, patients require limb amputation. Until recently, the only treatment option for such a lesion was an open surgery. However, a good skill level of endovascular surgeons and the device availability allow today to perform minimally invasive operations with comparable effectiveness and greater safety in comparison with open surgery. We present a case report of successful endovascular treatment of aortic occlusion involving the right and left common and external iliac arteries using Culotte stenting technique with further 12-month follow-up.

Neutrophil-To-Lymphocyte Ratio and Abdominal Aortic Atherosclerosis among Asymptomatic Individuals.

ResumoFundamento A razão neutrófilo-linfócito (RNL) tem sido proposta como um marcador inflamatório possivelmente associado a aterosclerose coronariana, embora a maioria dos dados atuais seja restrita à fase aguda. Além disso, a associação entre a RNL e a aterosclerose extracoronariana ainda não está clara.Objetivo Analisar a associação entre a RNL e aterosclerose da aorta abdominal (AtAA).Métodos Foram incluídos pacientes assintomáticos submetidos a um programa de rastreamento. A AtAA foi avaliada através de ultrassom. Os números absolutos de leucócitos e linfócitos foram utilizados para calcular a RNL. Foi estabelecido um nível de significância estatística de 0,05.Resultados De 36.985 indivíduos (idade: 42±10 anos, 72% homens), foi identificada a presença de AtAA em 7%. Aqueles com AtAA eram mais velhos e tinham maior propensão a serem homens e diabéticos. A presença de AtAA foi associada a RNL aumentada (odds ratio [OR] 1,17; intervalo de confiança de 95% [IC95%] 1,13-1,21). No entanto, a associação deixou de ser significativa quando a análise foi ajustada para os fatores de risco (OR 1,02; IC95% 0,97-1,06), principalmente devido à inclusão da idade no modelo. Quando os neutrófilos e linfócitos foram analisados separadamente, a associação negativa entre os linfócitos e a RNL foi invertida com a inclusão da idade, o que sugere um forte efeito confundidor da idade na relação entre linfócitos e aterosclerose. Por fim, a associação entre os neutrófilos e a AtAA deixou de ser significativa após o ajuste adicional para os fatores de risco tradicionais, mas não apenas para a idade.Conclusão Embora a RNL tenha se associado a AtAA, foi principalmente devido ao efeito confundidor da idade. No geral, os resultados sugerem um papel limitado da contagem de leucócitos como biomarcador de AtAA.

Differences of Gut Microbiota Diversity between Patients with Abdominal Aortic Aneurysm and Atherosclerosis

Objective To investigate the differences of gut microbiota between patients with abdominal aortic aneurysm and atherosclerosis.Methods From December 2018 to June 2019,20 fresh stool samples were collected respectively from the patients with abdominal aortic aneurysm and atherosclerosis treated at the Department of Vascular Surgery,Peking Union Medical College Hospital.The 16S rDNA high-throughput sequencing was employed to compare the composition,abundance,and α and β diversities of gut microbiota between the two disease groups,and further determine the significantly differential genera.Results The two groups had great similarities in the composition of gut microbiota.There was no statistical difference in α diversity.Although β diversity did not have statistically significant difference,certain microbial taxa showed differences between the two groups.The LEfSe demonstrated that the abdominal aortic aneurysm group had higher relative abundance of Leuconostocaceae,Ruminococcaceae,Weissella,and Faecalibacterium while lower relative abundance of Firmicuteria,Selenomonadales,and Veillonellaceae.Conclusion The structure of gut microbiota has differences between patients with abdominal aortic aneurysm and atherosclerosis,and sample size should be enlarged to validate the results.

Tryptophan Catabolism and Inflammation: A Novel Therapeutic Target For Aortic Diseases.

Aortic diseases are the primary public health concern. As asymptomatic diseases, abdominal aortic aneurysm (AAA) and atherosclerosis are associated with high morbidity and mortality. The inflammatory process constitutes an essential part of a pathogenic cascade of aortic diseases, including atherosclerosis and aortic aneurysms. Inflammation on various vascular beds, including endothelium, smooth muscle cell proliferation and migration, and inflammatory cell infiltration (monocytes, macrophages, neutrophils, etc.), play critical roles in the initiation and progression of aortic diseases. The tryptophan (Trp) metabolism or kynurenine pathway (KP) is the primary way of degrading Trp in most mammalian cells, disturbed by cytokines under various stress. KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), etc. Depends on the cell types, these metabolites can elicit both hyper- and anti-inflammatory effects. Accumulating evidence obtained from various animal disease models indicates that KP contributes to the inflammatory process during the development of vascular disease, notably atherosclerosis and aneurysm development. This review outlines current insights into how perturbed Trp metabolism instigates aortic inflammation and aortic disease phenotypes. We also briefly highlight how targeting Trp metabolic pathways should be considered for treating aortic diseases.