Features of infective native aortic aneurysms on computed tomography

Background Infective native aortic aneurysm (INAA) is a rare clinical diagnosis. The purpose of this study was to describe the CT findings of INAAs in detail. Methods This was a retrospective single-center study of INAA patients at a major referral hospital between 2005 and 2020. All images were reviewed according to a protocol consisting of aneurysm features, periaortic findings, and associated surrounding structures. Results One hundred and fourteen patients (mean age, 66 years [standard deviation, 11 years]; 91 men) with 132 aneurysms were included. The most common locations were infrarenal (50.8%), aortoiliac (15.2%), and juxtarenal (12.9%). The mean transaxial diameter was 6.2 cm. Most INAAs were saccular (87.9%) and multilobulated (91.7%). Calcified aortic plaque was present in 93.2% and within the aneurysm in 51.5%. INAA instability was classified as contained rupture (27.3%), impending rupture (26.5%), and free rupture (3.8%). Rapid expansion was demonstrated in 13 of 14 (92.9%) aneurysms with sequential CT studies. Periaortic inflammation was demonstrated as periaortic enhancement (94.7%), fat stranding (93.9%), soft-tissue mass (92.4%), and lymphadenopathy (62.1%). Surrounding involvement included psoas muscle (17.8%), spondylitis (11.4%), and perinephric region (2.8%). Twelve patients demonstrated thoracic and abdominal INAA complications: fistulas to the esophagus (20%), bronchus (16%), bowel (1.9%), and inferior vena cava (IVC) (0.9%). Conclusion The most common CT features of INAA were saccular aneurysm, multilobulation, and calcified plaques. The most frequent periaortic findings were enhancement, fat stranding, and soft-tissue mass. Surrounding involvement, including psoas muscle, IVC, gastrointestinal tract, and bronchi, was infrequent but may develop as critical INAA complications.

Cilengitide Inhibits Neovascularization in a Rabbit Abdominal Aortic Plaque Model by Impairing the VEGF Signaling

Background. Cilengitide is a selective αvβ3 and αvβ5 integrin inhibitor. We sought to investigate the effect of cilengitide on the neovascularization of abdominal aortic plaques in rabbits and explore its underlying antiangiogenic mechanism on human umbilical vein endothelial cells (HUVECs). Materials and Methods. For the in vivo experiment, the abdominal aortic plaque model of rabbits was established and injected with different doses of cilengitide or saline for 14 consecutive days. Conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) were applied to measure the vascular structure and blood flow parameters. CD31 immunofluorescence staining was performed for examining neovascularization. Relative expressions of vascular endothelial growth factor (VEGF) and integrin of the plaque were determined. For in vitro experiments, HUVECs were tested for proliferation, migration, apoptosis, and tube formation in the presence of different doses of cilengitide. Relative expressions of VEGF, integrin, and Ras/ERK/AKT signaling pathways were determined for the exploration of underlying mechanism. Results. CEUS showed modestly increased size and eccentricity index (EI) of plaques in the control group. Different degrees of reduced size and EI of plaques were observed in two cilengitide treatment groups. The expressions of VEGF and integrin in the plaque were inhibited after 14 days of cilengitide treatment. The neovascularization and apoptosis of the abdominal aorta were also significantly alleviated by cilengitide treatment. For in vitro experiments, cilengitide treatment was found to inhibit the proliferation, migration, and tube formation of HUVECs. However, cilengitide did not induce the apoptosis of HUVECs. A higher dose of cilengitide inhibited the mRNA expression of VEGF-A, β3, and β5, but not αV. Lastly, cilengitide treatment significantly inhibited the Ras/ERK/AKT pathway in the HUVECs. Conclusions. This study showed that cilengitide effectively inhibited the growth of plaque size by inhibiting the angiogenesis of the abdominal aortic plaques and blocking the VEGF-mediated angiogenic effect on HUVECs.

Down-regulation of microRNA-342-5p or Up-regulation of Wnt3a Inhibits Angiogenesis and Maintains Atherosclerotic Plaque Stability in Atherosclerosis Mice

Evidence has demonstrated that microRNA-342-5p (miR-342-5p) is implicated in atherosclerosis (AS), but little is known regarding its intrinsic regulatory mechanisms. Here, we aimed to explore the effect of miR-342-5p targeting Wnt3a on formation of vulnerable plaques and angiogenesis of AS. ApoE−/− mice were fed with high-fat feed for 16 w to replicate the AS vulnerable plaque model. miR-342-5p and Wnt3a expression in aortic tissues of AS were detected. The target relationship between miR-342-5p and Wnt3a was verified. Moreover, ApoE−/− mice were injected with miR-342-5p antagomir and overexpression-Wnt3a vector to test their functions in serum lipid levels, inflammatory and oxidative stress-related cytokines, aortic plaque stability and angiogenesis in plaque of AS mice. miR-342-5p expression was enhanced and Wnt3a expression was degraded in aortic tissues of AS mice and miR-342-5p directly targeted Wnt3a. Up-regulating Wnt3a or down-regulating miR-342-5p reduced blood lipid content, inflammatory and oxidative stress levels, the vulnerability of aortic tissue plaque and inhibited angiogenesis in aortic plaque of AS mice. Functional studies show that depleting miR-342-5p can stabilize aortic tissue plaque and reduce angiogenesis in plaque in AS mice via restoring Wnt3a.

TP53-mediated clonal hematopoiesis confers increased risk for incident peripheral artery disease

BackgroundSomatic mutations in blood indicative of clonal hematopoiesis of indeterminate potential (CHIP), particularly in DNMT3A, TET2, and JAK2, are associated with an increased risk of hematologic malignancy, coronary artery disease, and all-cause mortality. However, whether CHIP is associated with increased risk of peripheral artery disease (PAD) remains unknown. In addition, chemotherapy frequently causes mutations in DNA Damage Repair (DDR) genes TP53 and PPM1D, and whether CHIP caused by somatic mutations in DDR genes results in increased risk of atherosclerosis is unclear. We sought to test whether CHIP, and CHIP caused by DDR genes, associates with incident peripheral artery disease (PAD) and atherosclerosis.MethodsWe identified CHIP among 50,122 exome sequences in individuals from UK and Mass General Brigham Biobanks and tested CHIP status (N=2,851) with incident PAD and atherosclerosis across multiple arterial beds. To mimic the human scenario of clonal hematopoiesis and test whether the expansion of p53-deficient hematopoietic cells contributes to atherosclerosis, a competitive bone marrow transplantation (BMT) strategy was used to generate atherosclerosis-prone Ldlr-/- chimeric mice carrying 20% Trp53-/- hematopoietic cells (20% KO-BMT mice). We then evaluated aortic plaque burden and plaque macrophage accumulation 12 weeks after grafting.ResultsCHIP associated with incident PAD (HR 1.7; P=2.2x10-5) and atherosclerosis in multiple beds (HR 1.3; P=9.7x10-5), with increased risk among individuals with DDR CHIP (HR 2.0; P=0.0084). Among atherosclerosis-prone Ldlr null mice, the p53 -/- 20% KO-BMT mice demonstrated increased aortic plaque size (p=0.013) and accumulation of p53-/- plaque macrophages (P<0.001), driven by an abundance of p53-deficient plaque macrophages. The expansion of p53-deficient cells did not affect the expression of the pro-inflammatory cytokines IL-6 and IL-1β in the atherosclerotic aortic wall.ConclusionsOur findings highlight the role of CHIP as a broad driver of atherosclerosis across the entire arterial system, with evidence of increased plaque among p53 -/- 20% KO-BMT mice via expansion of plaque macrophages. These observations provide new insight into the link between CHIP and cardiovascular disease, and lend human genetic support to the concept that post-cytotoxic chemotherapy patients may benefit from surveillance for atherosclerotic conditions in addition to therapy-related myeloid neoplasms.

Parkin Dependent Mitophagy Protects Macrophage Against Oxidative Injury And Inflammation During Atherogenesis

Mitochondrial oxidative injury induces macrophage inflammatory activation and apoptosis during atherogenesis. Timely clearance of dysfunctional mitochondria may therefore be beneficial for the survival of macrophages. Based on these principles, our working hypothesis was therefore that mitophagy mediated by the E3 ubiquitin ligase Parkin could have an important role in reducing both oxidative injury and the apoptosis of macrophages under atherogenic conditions. To examine this proposal, in the present study oxidative low-density lipoprotein (ox-LDL) treated THP-1 macrophages were used for the in vitro experiments, and high-cholesterol-fed male apolipoprotein E knockout (ApoE−/−) mice were used for the in vivo investigations. The results demonstrated that mitophagy was activated both in oxidatively stimulated THP-1 macrophages and in aortic plaque macrophages of high-cholesterol-fed ApoE−/− mice. In ox-LDL treated THP-1 macrophages, both the expression level and mitochondrial translocation of Parkin were increased following oxidative stimulation, whereas silencing Parkin led to impaired mitophagy, which exacerbated macrophage oxidative injury, NF-κB activation and apoptosis. Taken together, these results have demonstrated that mitophagy exerts a protective role in macrophages under atherogenic conditions, and that Parkin is a key mediator in this process.

Hyperacute Incidental Late Myocardial Enhancement in Ischemic Stroke using Chest Spectral CT: Relationship with Etiology

PurposeHyperacute cardiac imaging of patients with acute ischemic stroke (AIS), though desirable, is impractical. Using delayed-enhancement, low-dose, non-gated, chest spectral computed tomography scans (DESCT), we explored the prevalence and patterns of incidental myocardial late iodine enhancement (LIE) and embolic sources, and the relationship with stroke etiology. MethodsSince July 2020, DESCT was performed after cerebrovascular CT angiography (CTA) among patients with suspected AIS undergoing CT using a dual-layer spectral scanner, without additional contrast administration. Images were analyzed using monoenergetic reconstructions and iodine density maps, and the myocardial extracellular volume fraction (ECV, %) was calculated. ResultsEighty consecutive patients with AIS were included. DESCT identified a cardiac thrombi in 6 patients (7.5%), and a complex aortic plaque in 4 (5%) cases; reclassifying 5 embolic strokes of uncertain source (28% of ESUS) to cardioembolic (CE, n=3) and non-CE (n=2) etiologies. LIE, most commonly ischemic (82%), was identified in 38 (48%) patients. We did not identify significant relationships between AIS etiology and the presence, pattern, and extension of LIE (p>0.05); ECV (p=0.56), severe aortic (p=0.25) or valvular (p=0.26) disease, or the extent of coronary calcification (p=0.39). Patients with evidence of major cardiovascular DESCT findings had higher rate rates of all-cause death at 90 days (42% vs. 19%, p=0.037). ConclusionIn this study, hyperacute cardiac imaging of AIS with DESCT identified a high prevalence of incidental cardiac disease predominantly involving LIE of ischemic etiology and mostly not related to the stroke etiology.

Theranostic Nanoplatform to Target Macrophages Enables the Inhibition of Atherosclerosis Progression and Fluorescence Imaging of Plaque

Background: Rupture of atherosclerotic plaque can cause acute malignant heart and cerebrovascular events, such as acute coronary heart disease, stroke and so on, which seriously threaten the safety of human life and property. Therefore, the early diagnosis and inhibition of atherosclerotic plaque progress still be a vital task. Results: In this study, we presented the development of composite mesoporous silica nanoparticle (CMSN) - based nanomedicines (NMs) (Ru(bpy)3@SiO2-mSiO2@SRT1720@ AntiCD36, CMSN@SRT@Anti) for accurate diagnosis and treatment of atherosclerosis. In vitro cell experiments showed that both RAW264.7 and ox-LDL-stimulated RAW264.7 cells could significantly uptake CMSN@SRT@Anti. Conversely, little fluorescence signal could be observed in CMSN@SRT group, showing the excellent targeting ability of CMSN@SRT@Anti to CD36 on macrophage. Additionally, such fluorescence signal was significantly stronger in ox-LDL-stimulated RAW264.7 cells, showing the ox-LDL can promote the upregulation of CD36 expression on macrophages to produce a stronger binding signal. For another, compared with free SRT1720, CMSN@SRT@Anti had a better and more significant effect on the inhibition of macrophage foaming process, which indicated that drug-carrying mesoporous silicon with targeting ability could enhance the efficacy of SRT1720. Animal experimental results showed that after the abdominal injection of CMSN@SRT@Anti, the aortic lesions of ApoE-/-mice could be observed with obvious and persistent fluorescence signals. After 4 weeks post- treatment, the serum total cholesterol, aortic plaque status and area were significantly improved in the mouse, and the effect was better than that in the free SRT1720 group or the CMSN@SRT group. Conclusions: The designed CMSN@SRT@Anti with excellent biocompatibility, high-performance and superior atherosclerosis-targeting ability has great potential for accurate identification and targeted therapy of atherosclerotic diseases.

Assessment of risk factors for postoperative cognitive dysfunction after coronary artery bypass surgery: a single-center retrospective cohort study

Aim: To find out risk factors for postoperative cognitive dysfunction (POCD) after coronary artery bypass grafting (CABG), and to provide basis for clinical prevention of POCD. A total of 88 patients who underwent CABG were surveyed with Telephone Questionnaire (TICS-M) for their cognitive impairment after 3, 7, 21, 90, 180 days post-surgery. The occurrence of POCD was diagnosed by Neuropsychological Battery which included Vocabular Learning Test (VLT), Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT) and Symbol Digit Modalities Test (SDMT). The preoperative, intraoperative and postoperative risk factors were assessed by the χ2 or t test. Multivariate analysis was used to study the correlation between the risk factors and the occurrence of POCD. Age, aortic plaque, carotid artery stenosis, cerebrovascular disease, anesthesia time, the rate of decline in intraoperative hemoglobin concentration (ΔHb) and systemic inflammatory response syndrome (SIRS) score on postoperative day 2 had statistically significant (P&lt;0.05) influence on the occurrence of POCD. Aortic plaque, carotid artery stenosis, anesthesia time and SIRS score (odds ratio (OR) value &gt; 1, P&lt;0.05) are the risk factors for POCD. The incidence of day-21 and -180 POCD was approximately 26.1 and 22.7%, respectively.