Abdominal Aortic Wall Research Articles

Perivascular scaffolds loaded with adipose tissue-derived stromal cells attenuate development and progression of abdominal aortic aneurysm in rats.

Abdominal aortic aneurysm (AAA) is the pathological dilation and weakening of the abdominal aorta wall. Inflammation, degradation of the extracellular matrix (ECM) and loss of smooth muscle cells and skewing of their function are pivotal in AAA pathology. We developed a recombinant collagen-based patch (RCP) to provide structural integrity and deliver Adipose tissue-Derived Stromal Cells (ASC) for repair. Patches supported adhesion and function as well as proliferation of ASC. ASC-loaded RCPs or bare patches, applied around the aorta after AAA induction in rats, both maintained structural integrity of the aortic wall at time of explant (2w). However, wall thinning, accompanied by loss of elastin fibers and loss of medial SMC, was only attenuated in ASC-loaded RCP-treated AAA rats. Interestingly, this coincided with migration of ASC into the media and a reduced influx of macrophages. We hypothesize that the medially-migrated ASC dampened or skewed the adverse innate immunity and thus suppressed SMC apoptosis, phenotypic skewing and elastin degradation. We conclude that the periadventitial delivery of ASC with RCP suppresses development and progression of AAA, which is has an expected future clinical benefit in combination with an appropriate early screening program of patients at risk for aneurysms. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2494-2506, 2018.

Dual-Targeted Theranostic Delivery of miRs Arrests Abdominal Aortic Aneurysm Development.

Abdominal aortic aneurysm (AAA) is an often deadly disease without medical, non-invasive treatment options. The upregulation of vascular cell adhesion molecule-1 (VCAM-1) on aortic endothelium provides an early target epitope for a novel biotechnological theranostic approach. MicroRNA-126 was used as a therapeutic agent, based on its capability to downregulate VCAM-1 expression in endothelial cells and thereby reduces leukocyte adhesion and exerts anti-inflammatory effects. Ultrasound microbubbles were chosen as carriers, allowing both molecular imaging as well as targeted therapy of AAA. Microbubbles were coupled with a VCAM-1-targeted single-chain antibody (scFvmVCAM-1) and a microRNA-126 mimic (M126) constituting theranostic microbubbles (TargMB-M126). TargMB-M126 downregulates VCAM-1 expression in vitro and in an in vivo acute inflammatory murine model. Most importantly, using TargMB-M126 and ultrasound-guided burst delivery of M126, the development of AAA in an angiotensin-II-induced mouse model can be prevented. Overall, we describe a unique biotechnological theranostic approach with the potential for early diagnosis and long-sought-after medical therapy of AAA.

Shortening tends to increase aortic foam cell count and wall thickness in male Wistar rats

BackgroundShortening is widely used as raw material for bread and other foods. Hypercholesterolemia increases aortic arch foam cell formation and abdominal aortic wall thickness. This study aimed to determine the effect of shortening on the number of aortic arch foam cells and abdominal aortic wall thickness in rats.MethodsThis study was of experimental posttest control group design. Twenty four male Wistar rats were randomized into 4 groups. The negative control group (C-) received standard feed, the positive control group (C+) standard high-fat feed, group T1 shortening and standard feed at a ratio of 1:5 and group T2 shortening and standard feed at a ratio of 1:10. The interventions were given for 6 weeks through gavage. The foam cell count in the aortic arch and the thickness of the abdominal aortic wall were measured. One-way ANOVA test was used to analyze the data. ResultsThere was no significant difference in the mean foam cell count of the aortic arch between the four groups C- (7.17 ± 4.17), C + (9.33 ± 7.01), T1 (11.83 ± 4.88) and T2 (9.33 ± 6.80) (p=0.598). The mean thickness of the abdominal aortic wall between the four groups C- (741.98 ± 60.67μm), C + (714.29 ± 90.59μm), T1 (838.90 ± 75.86 μm), and T2 (749.88 ± 99.37μm) also was not significantly different (p=0.110).Conclusion Shortening tends to increase the foam cell count of the aortic arch and the thickness of the abdominal aortic wall of rats.

Features of manifestation and progression for critical lower limb ischemia in subjects with abdominal aortic calcification: a pilot study

Aim. The study was designed to assess the specific features of manifestation and progression for critical low limb ischemia in patients with abdominal aortic calcification. Methods. The total of 151 patients with low limb critical ischemia due to peripheral arterial disease were enrolled to the study cohort: 79 patients (study group) with abdominal aortic calcification and 72 patients (control group) without any signs of abdominal aortic wall calcification. Abdominal aortic calcification was detected by CT-imaging. The patients with diabetes mellitus and with chronic renal insufficiency were excluded from the study cohort. Results. Critical lower limb ischemia in subjects with abdominal aortic calcification manifested itself in the following features: predominant localization of lesions in the aorto-iliac position (68.4% vs. 33.3% in patients without abdominal aortic calcification; р<0.05), rapid progression of lower limb ischemia (its prevalence in the study group was 77.7% vs. 37.3% in the control group; р<0.01), expressed hypercoagulation combined with a decrease in the level of natural anticoagulants concentration (mean activity of antithrombin III in individuals with abdominal aortic calcification was 56.5±10.4% vs. 98.7±16.4% in patients without abdominal aortic calcification; р<0.001). Conclusion. The study findings have shown that critical lower limb ischemia in subjects with abdominal aortic calcification has specific futures of manifestation and clinical course that need to be considered when choosing the best treatment strategy.Received 24 April 2017. Revised 7 June 2017. Accepted 19 June 2017.Funding: The study did not have sponsorship.Conflict of interest: The authors declare no conflict of interest.

On the effect of computed tomography resolution to distinguish between abdominal aortic aneurysm wall tissue and calcification: A proof of concept

PurposeThe purpose of this study is to determine the optimal target CT spatial resolution for accurately imaging abdominal aortic aneurysm (AAA) wall characteristics, distinguishing between tissue and calcification components, for an accurate assessment of rupture risk. Materials and methodsRuptured and non-ruptured AAA-wall samples were acquired from eight patients undergoing open surgical aneurysm repair upon institutional review board approval and informed consent was obtained from all patients. Physical measurements of AAA-wall cross-section were made using scanning electron microscopy. Samples were scanned using high resolution micro-CT scanning. A resolution range of 15.5–155μm was used to quantify the influence of decreasing resolution on wall area measurements, in terms of tissue and calcification. A statistical comparison between the reference resolution (15.5μm) and multi-detector CT resolution (744μm) was also made. ResultsElectron microscopy examination of ruptured AAAs revealed extremely thin outer tissue structure <200μm in radial distribution which is supporting the aneurysm wall along with large areas of adjacent medial calcifications far greater in area than the tissue layer. The spatial resolution of 155μm is a significant predictor of the reference AAA-wall tissue and calcification area measurements (r=0.850; p<0.001; r=0.999; p<0.001 respectively). The tissue and calcification area at 155μm is correct within 8.8%±1.86 and 26.13%±9.40 respectively with sensitivity of 87.17% when compared to the reference. ConclusionThe inclusion of AAA-wall measurements, through the use of high resolution-CT will elucidate the variations in AAA-wall tissue and calcification distributions across the wall which may help to leverage an improved assessment of AAA rupture risk.

Human hepatocyte growth factor inhibits early neointima formation in rabbit abdominal aortae following ultrasound-guided balloon injury.

The present study investigated the effects of in vivo gene transfer of human hepatocyte growth factor (hHGF) on neointima formation in rabbit abdominal aortae following ultrasound-guided balloon injury. New Zealand white rabbits were randomly divided into four groups: endothelium injury alone (EI), endothelium injury with control vector transfection (EI–V), endothelium injury with hHGF transfection (EI-HGF), and hHGF transfection alone without endothelium injury (HGF). Endothelial injury was established by scraping the abdominal aortic wall using a balloon catheter under the guidance of a transabdominal ultrasound. hHGF gene transfer was performed 7 days following injury. hHGF mRNA and protein expression levels were determined at 3, 7, 14 and 21 days following transfection. Neointima formation was assessed by histopathological analysis at 14 and 28 days following injury. hHGF mRNA and protein expression levels were detected in the target abdominal aortae in EI-HGF and HGF groups with the greatest levels observed 3 days following transfection, and their levels dropped below detection limits at 21 days following transfection. hHGF was not detectable in the EI and EI-V groups throughout the experiment. The neointimal area and the neointima to media ratio in the EI-HGF group were significantly decreased compared with those in the EI or EI-V group at 14 days following injury. However, no differences were observed at 28 days following injury. The present study demonstrated that in vivo hHGF gene transfer inhibits the early formation of neointima in balloon-injured rabbit abdominal aortae.

Is aortic aneurysm preventable?

Abdominal aortic aneurysm (AAA) is a chronic inflammatory condition, triggered by the local accumulation of macrophages, oxidative stress and damage to the aortic wall. Pro-inflammatory eicosanoids seem to play a significant role in AAA. The pro-inflammatory events seen in AAA could be due to a deficiency of anti-inflammatory eicosanoids such as lipoxin A4 (LXA4), resolvins, protectins and maresins as a result of reduced tissue concentrations of their precursors: arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Thus, an imbalance between pro- and anti-inflammatory eicosanoids may underlie AAA. Angiotensin-II (Ang-II), a pro-inflammatory molecule, seems to have a role in AAA. I propose that AAA is due to the local (abdominal aortic wall) deficiency of AA and other PUFAs and their anti-inflammatory metabolites especially LXA4. The beneficial action of EPA and DHA reported in the animal experimental models of AAA induced by Ang-II infusion can be attributed to their (EPA and DHA) ability to enhance the formation of not only resolvins, protectins and maresins but also LXA4. It is likely that abdominal aortic tissue (endothelial cells, smooth muscle cells and other cells) may be deficient in AA, EPA and DHA, and have defective activity of 5-, 12-, and 15-lipoxygenases and cyclooxygenase, especially COX-2 resulting in decreased formation of LXA4, resolvins, protectins and maresins. Thus, methods designed to enhance the formation of LXA4 and other anti-inflammatory eicosanoids may form a new approach to prevent and manage AAA.

The Relationship Between Surface Curvature and Abdominal Aortic Aneurysm Wall Stress.

The maximum diameter (MD) criterion is the most important factor when predicting risk of rupture of abdominal aortic aneurysms (AAAs). An elevated wall stress has also been linked to a high risk of aneurysm rupture, yet is an uncommon clinical practice to compute AAA wall stress. The purpose of this study is to assess whether other characteristics of the AAA geometry are statistically correlated with wall stress. Using in-house segmentation and meshing algorithms, 30 patient-specific AAA models were generated for finite element analysis (FEA). These models were subsequently used to estimate wall stress and maximum diameter and to evaluate the spatial distributions of wall thickness, cross-sectional diameter, mean curvature, and Gaussian curvature. Data analysis consisted of statistical correlations of the aforementioned geometry metrics with wall stress for the 30 AAA inner and outer wall surfaces. In addition, a linear regression analysis was performed with all the AAA wall surfaces to quantify the relationship of the geometric indices with wall stress. These analyses indicated that while all the geometry metrics have statistically significant correlations with wall stress, the local mean curvature (LMC) exhibits the highest average Pearson's correlation coefficient for both inner and outer wall surfaces. The linear regression analysis revealed coefficients of determination for the outer and inner wall surfaces of 0.712 and 0.516, respectively, with LMC having the largest effect on the linear regression equation with wall stress. This work underscores the importance of evaluating AAA mean wall curvature as a potential surrogate for wall stress.

Phenotype-based selection of bone marrow mesenchymal stem cell-derived smooth muscle cells for elastic matrix regenerative repair in abdominal aortic aneurysms.

Chronic proteolytic disruption of elastic fibres within the abdominal aortic wall results in wall vessel expansion to form rupture-prone abdominal aortic aneurysms (AAA). Arresting AAA growth is not possible as adult vascular smooth muscle cells (SMCs) poorly auto-regenerate and repair elastic fibres. Thus, there is a need to identify alternate cell sources capable of robust elastic matrix assembly to overcome elastolysis in the AAA wall. Previously, we demonstrated the superior elastogenic properties of rat bone marrow mesenchymal stem cell (BM-MSC)-derived SMCs (BM-SMCs) relative to aneurysmal and healthy rat aortic SMCs. In the present study, we investigate how phenotypic coordinates of the derived BM-SMCs, in turn dependent on conditions of BM-MSC differentiation, impact their elastic matrix synthesis abilities. More specifically, we investigated how glucose content, serum levels and the presence of transforming growth factor (TGF)-β1 supplements alone or together with platelet-derived growth factor (PDGF-BB) in the differentiation medium influence phenotype of, and elastogenesis by derived rat BM-SMCs. BM-SMCs generated in low-glucose and 10% v/v serum conditions in the presence of TGF-β1 with or without PDGF-BB exhibited a mature phenotype characterized by contractility and migrative tendencies similar to healthy rat aortic SMCs, and yet capable of robust tropoelastin (precursor) synthesis and assembly of a fibrous, highly crosslinked elastic matrix. Thus, we have identified metrics and conditions for selecting BM-SMCs with superior elastogenesis for in situ elastic matrix regeneration. Future studies will focus on characterizing these specific BM-SMC subtypes for their pro-elastogenic and anti-proteolytic effects on aneurysmal SMCs to confirm their preferred use for therapy aimed at AAA tissue regenerative repair. Copyright © 2016 John Wiley & Sons, Ltd.

Free-breathing black-blood CINE fast-spin echo imaging for measuring abdominal aortic wall distensibility: a feasibility study

The paper reports a free-breathing black-blood CINE fast-spin echo (FSE) technique for measuring abdominal aortic wall motion. The free-breathing CINE FSE includes the following MR techniques: (1) variable-density sampling with fast iterative reconstruction; (2) inner-volume imaging; and (3) a blood-suppression preparation pulse. The proposed technique was evaluated in eight healthy subjects. The inner-volume imaging significantly reduced the intraluminal artifacts of respiratory motion (p = 0.015). The quantitative measurements were a diameter of 16.3 ± 2.8 mm and wall distensibility of 2.0 ± 0.4 mm (12.5 ± 3.4%) and 0.7 ± 0.3 mm (4.1 ± 1.0%) for the anterior and posterior walls, respectively. The cyclic cross-sectional distensibility was 35 ± 15% greater in the systolic phase than in the diastolic phase. In conclusion, we developed a feasible CINE FSE method to measure the motion of the abdominal aortic wall, which will enable clinical scientists to study the elasticity of the abdominal aorta.

Myostatin mediates abdominal aortic atherosclerosis progression by inducing vascular smooth muscle cell dysfunction and monocyte recruitment

Myostatin (Mstn) is a skeletal muscle growth inhibitor involved in metabolic disorders and heart fibrosis. In this study we sought to verify whether Mstn is also operative in atherosclerosis of abdominal aorta. In human specimens, Mstn expression was almost absent in normal vessels, became detectable in the media of non-progressive lesions and increased with the severity of the damage. In progressive atherosclerotic lesions, Mstn was present in the media, neointima, plaque shoulder and in infiltrating macrophages. Mstn co-localized with α-smooth muscle actin (α-SMA) staining and with some CD45+ cells, indicating Mstn expression in VSMCs and bloodstream-derived leukocytes. In vitro, Mstn was tested in VSMCs and monocytes. In A7r5 VSMCs, Mstn downregulated proliferation and Smoothelin mRNA, induced cytoskeletal rearrangement, increased migratory rate and MCP-1/CCR2 expression. In monocytes (THP-1 cells and human monocytes), Mstn acted as a chemoattractant and increased the MCP-1-dependent chemotaxis, F-actin, α-SMA, MCP-1 and CCR2 expression; in turn, MCP-1 increased Mstn mRNA. Mstn induced JNK phosphorylation both in VSMCs and monocytes. Our results indicate that Mstn is overexpressed in abdominal aortic wall deterioration, affects VSMCs and monocyte biology and sustains a chronic inflammatory milieu. These findings propose to consider Mstn as a new playmaker in atherosclerosis progression.

The water channel AQP1 is expressed in human atherosclerotic vascular lesions and AQP1 deficiency augments angiotensin II-induced atherosclerosis in mice.

The water channel aquaporin 1 (AQP1) promotes endothelial cell migration. It was hypothesized that AQP1 promotes neovascularization and growth of atherosclerotic plaques. AQP1 immunoreactivity and protein abundance was examined in human and murine atherosclerotic lesions and aortic aneurysms. Apolipoprotein E (ApoE) knockout (-/-) and AQP1-/-ApoE-/- mice were developed and fed Western diet (WD) for 8 and 16weeks to accelerate the atherosclerosis process. In ApoE-/- and AQP1-/-ApoE-/- mice abdominal aortic aneurysms (AAA) were induced by angiotensin II (ANGII) infusion by osmotic minipumps for 4weeks. In human atherosclerotic lesions and AAA, AQP1 immunoreactive protein was associated with intralesional small vessels. In ApoE-/- mouse aorta, APQ1 mRNA levels were increased with time on WD (n=7-9, P<0.003). Both in murine lesions at the aortic root and in the abdominal aortic aneurysmal wall, AQP1 immunoreactivity was associated with microvascular structures. The atherosclerotic lesion burden was enhanced significantly in ANGII-infused AQP1-/-ApoE-/- mice compared with ApoE-/- mice, but neither incidence nor progression of AAA was different. The aortic lesion burden increased with time on WD but was not different between ApoE-/- and AQP1-/-ApoE-/- mice at either 8 or 16weeks (n=13-15). Baseline blood pressure and ANGII-induced hypertension were not different between genotypes. AQP1 is expressed in atherosclerotic lesion neovasculature in human and mouse arteries and AQP1 deficiency augments lesion development in ANGII-promoted atherosclerosis in mice. Normal function of AQP1 affords cardiovascular protection.

Effect of Bortezomib on Angiotensin Ⅱ-induced Abdominal Aortic Aneurysm in ApoE-/- Mice.

Objective To investigate the role of proteasome inhibitor bortezomib (BTZ) in inflammatory response in abdominal aortic aneurysm (AAA) formation induced by angiotensin Ⅱ (Ang Ⅱ). Methods Ang Ⅱ-induced ApoE-/- mice AAA models were established. Forty male ApoE-/- mice (8-10-week-old) were randomly and equally divided into four groups:Sham group,BTZ group,Ang Ⅱ group,and Ang Ⅱ+BTZ group.HE staining,immunohistochemical staining,and flow cytometry were used to analyze the inflammatory response. Real-time quantitative polymerase chain reaction (qPCR) was used to analyze the mRNA expression of intercellular cell adhesion molecule-1 (ICAM-1). Western blotting was used to analyze the activation of nuclear factor κB signaling (NF-κB). Results The mean maximum suprarenal aortic diameter (Dmax) of Sham group,BTZ group,Ang Ⅱ group,and Ang Ⅱ+BTZ group were (1.00±0.01),(0.99±0.01),(1.50±0.13),and (1.20±0.04)mm,respectively (F=8.959,P=0.000). The Dmax of Ang Ⅱ group was significantly larger than those of Sham group (P=0.000) and Ang Ⅱ+BTZ group (P=0.015). The incidence of AAA in Ang Ⅱ group,Ang Ⅱ+BTZ group,and Sham group were 60%,17%,and 0,respectively. HE staining revealed that the abdominal aortic wall thickening was more severe in Ang Ⅱ group than in Sham group and Ang Ⅱ+BTZ group,similar with the infiltration of inflammatory cells. Immunohistochemical staining demonstrated that the CD3+T lymphocyte count was significantly higher in Ang Ⅱ group than in Sham group (107.9±15.9 vs. 0,P=0.000) and Ang Ⅱ+BTZ group (107.9±15.9 vs. 0.8±0.5,P=0.000). Flow cytometry also demonstrated that the proportion of the CD3+T lymphocytes of the Ang Ⅱ group [(13.50±0.69)%] was significantly higher than that in the Ang Ⅱ+BTZ group [(10.40±0.78)%] at week 1 (t=3.009,P=0.040),and the proportion of the CD3+T lymphocytes of the Ang Ⅱ group [(22.70±0.93)%] was significantly higher than that in the Ang Ⅱ+BTZ group [(15.10±0.97)%] at week 4 (t=5.654,P=0.005). The qPCR analysis showed that the mRNA expression of ICAM-1 was significantly up-regulated in Ang Ⅱ group than in Sham group (1.93±0.54 vs. 1.00±0.15,P=0.011) and Ang Ⅱ+BTZ group (1.93±0.54 vs. 0.83±0.08,P=0.009). Western blot analysis showed a lower phosphorylation level of inhibitor of NF-κB in the Ang Ⅱ group compared with the Sham group or Ang Ⅱ+BTZ group,accompanied with an increased phosphorylation level of p65. Conclusion Proteasome inhibitor BTZ can attenuate AAA formation partially by regulating T lymphocytes infiltration through regulating the mRNA expression of ICAM-1 regulated by the activation of NF-κB signaling pathway.

腹部大動脈瘤術後10年目に手術した人工血管周囲血腫拡大の1例

腹部大動脈瘤術後，腰動脈からの出血のために人工血管を被覆した瘤壁が拡大し，術後10年目に再手術を施行した稀な1例を経験したので報告する．症例は78歳の男性，68歳時に90mmの腎動脈下腹部大動脈瘤に対し人工血管置換術が施行された．術後1カ月目のCTで少量の血腫が人工血管周囲に認められていたが，6年目の腹部CTでも血腫は消失せず，術後10年目には62mmに拡大したため再手術を施行した．被覆した瘤壁を切開すると，壁内に多量の赤色血栓が認められた．出血源は前回手術で処置されていたと思われる腰動脈であった．今回の原因として，一旦止血されていた腰動脈から術後比較的早期に再出血し，被覆瘤壁が拡大したと思われた．また，腹部大動脈瘤術後に7年後に頸動脈血栓内膜摘除を施行され，その後，抗血小板剤を投与されたことは瘤壁拡大に拍車をかけたと思われた．

The Relation of Intra-Abdominal Adipose Tissue Accumulation and the Development of Vulnerable Carotid Atherosclerotic Plaques in Diabetes Mellitus.

Objective: The aim of study was determining the relation between the quality of metabolic control, anthropometric parameters and ultrasound measurement of fat accumulation and carotid atherosclerotic plaques vulnerability in patients with type 2 diabetes. Methods: The study included 51 patients with type 2 diabetes mellitus and 50 healthy individuals. The assessment of plaque vulnerability relies on quantitative and qualitative plaque ultrasound analysis. The thickness of intraabdominal adipose tissue was measured as a distance between the frontal wall of abdominal aorta and the dorsal wall of rectus abdominis muscles; the measurements are performed by placing transducer 5 cm above the umbilicus. Results: Atherosclerotic plaque was found in all of diabetic patients, comparing to 28.12% in the control group; among those, 47.06% with diabetes and 25.6% of control patients had vulnerable plaque. The vulnerability of atherosclerotic plaque was significantly related to age, duration of diabetes, glycaemia, waist circumference, waist / hip ratio, intra-abdominal adipose tissue thickness, intra-abdominal/subcutaneous fat ratio, dyslipidemia and hypertension. Conclusions: Carotid atherosclerotic plaques, particularly vulnerable ones, are far more prevalent in diabetic patients. Advanced age, poor glycemic control, obesity and the intra-abdominal fat accumulation contribute to carotid atherosclerotic plaques vulnerability. Despite the significant correlations with metabolic/anthropometric measurements, none of the predisposing factors could be identified as the independent risk factor; obviously, the increased vulnerability of has been the result of the synergistic effects of multiple pathogenic mechanisms. Moreover, ultrasound measurements of intra-abdominal fat did not show a decisive advantage over the classical anthropometric measurements in estimating atherosclerotic and metabolic risk.

High Dietary Fructose Intake on Cardiovascular Disease Related Parameters in Growing Rats.

The objective of this study was to determine the effects of a high-fructose diet on cardiovascular disease (CVD)-related parameters in growing rats. Three-week-old female Sprague Dawley rats were randomly assigned to four experimental groups; a regular diet group (RD: fed regular diet based on AIN-93G, n = 8), a high-fructose diet group (30Frc: fed regular diet with 30% fructose, n = 8), a high-fat diet group (45Fat: fed regular diet with 45 kcal% fat, n = 8) or a high fructose with high-fat diet group (30Frc + 45Fat, fed diet 30% fructose with 45 kcal% fat, n = 8). After an eight-week treatment period, the body weight, total-fat weight, serum glucose, insulin, lipid profiles and pro-inflammatory cytokines, abdominal aortic wall thickness, and expressions of eNOS and ET-1 mRNA were analyzed. The result showed that total-fat weight was higher in the 30Frc, 45Fat, and 30Frc + 45Fat groups compared to the RD group (p < 0.05). Serum triglyceride (TG) levels were highest in the 30Frc group than the other groups (p < 0.05). The abdominal aorta of 30Frc, 45Fat, and 30Frc + 45Fat groups had higher wall thickness than the RD group (p < 0.05). Abdominal aortic eNOS mRNA level was decreased in 30Frc, 45Fat, and 30Frc + 45Fat groups compared to the RD group (p < 0.05), and also 45Fat and 30Frc + 45Fat groups had decreased mRNA expression of eNOS compared to the 30Frc group (p < 0.05). ET-1 mRNA level was higher in 30Frc, 45Fat, and 30Frc + 45Fat groups than the RD group (p < 0.05). Both high fructose consumption and high fat consumption in growing rats had similar negative effects on CVD-related parameters.

Development of Polymer Microcapsules Functionalized with Fucoidan to Target P-Selectin Overexpressed in Cardiovascular Diseases.

New tools for molecular imaging and targeted therapy for cardiovascular diseases are still required. Herein, biodegradable microcapsules (MCs) made of polycyanoacrylate and polysaccharide and functionalized with fucoidan (Fuco-MCs) are designed as new carriers to target arterial thrombi overexpressing P-selectin. Physicochemical characterizations demonstrated that microcapsules have a core-shell structure and that fucoidan is present onto the surface of Fuco-MCs. Furthermore, their sizes range from 2 to 6 µm and they are stable on storage over 30 d at 4 °C. Flow cytometry experiments evidenced the binding of Fuco-MCs for human activated platelets as compared to MCs (mean fluorescence intensity: 12 008 vs. 9, p < 0.001) and its absence for nonactivated platelets (432). An in vitro flow adhesion assay showed high specific binding efficiency of Fuco-MCs to P-selectin and to activated platelet aggregates under arterial shear stress conditions. Moreover, both types of microcapsules reveal excellent compatibility with 3T3 cells in cytotoxicity assay. One hour after intravenous injection of microcapsules, histological analysis revealed that Fuco-MCs are localized in the rat abdominal aortic aneurysm thrombotic wall and that the binding in the healthy aorta is low. In conclusion, these microcapsules appear as promising carriers for targeting of tissues characterized by P-selectin overexpression and for their molecular imaging or treatment.

Assessment of abdominal aortic calcification at different stages of chronic kidney disease.

Vascular calcifications that may cause cardiovascular disease are highly prevalent in chronic kidney disease (CKD). In this study, we aimed to determine abdominal aorta calcifications (AAC) in predialysis and hemodialysis patients by lateral lumbar radiography and to investigate factors that were associated with the calcifications. Two hundred and fifty-nine adult chronic hemodialysis patients, 300 predialysis CKD patients and 60 healthy subjects with normal kidney function as a control group were enrolled in the study. Lateral lumbar radiography was used to measure AAC. Calcified deposits of the abdominal aorta wall at the level of the first through fourth lumbar vertebrae were graded by a 24-point scoring system. AAC prevalence (AAC score ≥1) was significantly different in hemodialysis, predialysis and control groups (71.8, 45.7 and 33.3%, respectively; p<0.001). AAC prevalence in CKD stages 1, 2, 3, 4 and 5 predialysis patients was 26.6, 43.3, 40, 58.3 and 55%, respectively. AAC scores of the hemodialysis group were higher than of the predialysis group (p<0.001) and the control group (p<0.001). AAC scores of the predialysis group were not higher than of the control group (p=0.314). AAC scores of the hemodialysis group were significantly higher than of the control group (p<0.001) and stage 1 (p<0.001), stage 2 (p=0.001) and stage 3 predialysis groups (p=0.002). Age (p<0.001), presence of diabetes mellitus (p<0.001) and serum phosphorus levels (p=0.011) were found to be independent predictors of calcification in the hemodialysis group. Age (p<0.001), serum phosphorus levels (p=0.007) and history of cardiovascular disease (p=0.014) were found to be independent predictors of calcification in the predialysis group. Abdominal aortic calcification is highly prevalent in the hemodialysis population. Strict phosphorus control should be implemented to the predialysis and hemodialysis patients.

Noninvasive Estimation of Aneurysm Sac Pressurization Following Endovascular Aneurysm Repair Using M-Mode Ultrasonography to Evaluate Significance of Endoleaks

Purpose: To establish the feasibility of indirectly estimating aneurysm sac pressurization from recordings of aortic pulsatile wall motion (PWM) using M-mode ultrasonography before and after endovascular aneurysm repair (EVAR). Methods: Twenty consecutive patients (mean age 72 years; 19 men) scheduled for EVAR in a single institution underwent M-mode ultrasonography 1 day before EVAR to record PWM of the abdominal aortic aneurysm wall during the cardiac cycle, along with simultaneous blood pressure measurements. The recording was repeated the first postoperative day. Pressure-strain elastic modulus (Ep) was calculated from the preoperative displacement and pressure data. This value and the postoperative PWM were used to inverse estimate pulse pressure in the abdominal aortic aneurysm sac post EVAR. Immediate pressure reduction post EVAR was compared between groups of endoleak vs no endoleak and expansion vs no expansion during 6-month follow-up. Results: Intraobserver variability of the method presented a mean value of 0.04 mm with a 1.2-mm coefficient of variation (95% limits of agreement −1.16 to 1.24 mm). PWM was significantly reduced postoperatively (1.2 vs 0.3 mm, p<0.001) as was pulse pressure exerted on the aneurysm sac (67 vs 16 mm Hg, p<0.001). The pressure reduction was similar between the endoleak vs no endoleak groups (79% vs 75%, p=0.65), but it was significantly greater in the no expansion group (79.5%) vs the group with aneurysm expansion (50%, p=0.008). Conclusion: M-mode ultrasonography may provide a useful adjunct during EVAR surveillance to noninvasively estimate sac pressurization and identify aneurysms at risk of enlargement.

Inflammatory cells, ceramides, and expression of proteases in perivascular adipose tissue adjacent to human abdominal aortic aneurysms

Abdominal aortic aneurysm (AAA) is a deadly irreversible weakening and distension of the abdominal aortic wall. The pathogenesis of AAA remains poorly understood. Investigation into the physical and molecular characteristics of perivascular adipose tissue (PVAT) adjacent to AAA has not been done before and is the purpose of this study. Human aortae, periaortic PVAT, and fat surrounding peripheral arteries were collected from patients undergoing elective surgical repair of AAA. Control aortas were obtained from recently deceased healthy organ donors with no known arterial disease. Aorta and PVAT was found in AAA to larger extent compared with control aortas. Immunohistochemistry revealed neutrophils, macrophages, mast cells, and T-cells surrounding necrotic adipocytes. Gene expression analysis showed that neutrophils, mast cells, and T-cells were found to be increased in PVAT compared with AAA as well as cathepsin K and S. The concentration of ceramides in PVAT was determined using mass spectrometry and correlated with content of T-cells in the PVAT. Our results suggest a role for abnormal necrotic, inflamed, proteolytic adipose tissue to the adjacent aneurysmal aortic wall in ongoing vascular damage.