Wall Inflammation Research Articles

Vessel wall imaging and quantitative flow assessment in arteriovenous malformations: A feasibility study.

Cerebral arteriovenous malformations (AVMs) carry a rupture rate of 2-3% per year. Several architectural factors may influence rupture rate, and a recently theorized model of AVMs describes the influence of vessel wall inflammation. A novel imaging modality, vessel wall imaging (VWI), has been developed to view inflammatory processes in vessel wall foci but has not yet been examined in AVMs, which is the aim of this study. This retrospective review studies prospectively collected data on patients with ruptured and unruptured AVMs between 2019 and 2021. Inclusion criteria included adult patients (≥18 years) with radiographically diagnosed AVM who underwent VWI. Charts were reviewed for medical history, clinical presentation, hospital course, discharge condition, and follow-up. Angioarchitectural features, blood flow, and VWI were compared in patients with and without hemorrhagic patients. Nine patients underwent VWI, mean age 37.7 ± 9.9 years. Four presented with hemorrhage (44.4%). Seven (77.7%) received glue embolization and 6 (66.7%) underwent surgical resection. All patients (4/4) with a history of hypertension presented with hemorrhage (p = 0.0027). Size and Spetzler-Martin grade were not associated with hemorrhage (p = 0.47, p = 0.59). Net AVM flow was higher in patients presenting with hemorrhage, although nonsignificant (p = 0.19). With VWI, 3 (75%) hemorrhagic AVMs showed visible nidus and draining veins, and all three demonstrated positive post-contrast wall enhancement in at least one of their draining veins; conversely, of fivenonhemorrhagic AVMs, only 2 (40%) demonstrated post-contrast wall enhancement in any draining vein (p = 0.090). This pilot study successfully demonstrated capture of venous walls in AVMs using VWI. In this study, draining vein enhancement occurred more often in hemorrhagic AVM and in those with higher venous volumetric flow.

First case of successful usage of a low-profile flow-diverting stent for treatment of intracranial infectious aneurysm in patient with a mechanical heart valve. Clinical case and literature review

Infectious aneurysms (IA) are cerebral aneurysms that are formed due to the infectious inflammation of the arterial wall. They are a rather rare pathology and in most cases prove to be a complication of infectious (bacterial) endocarditis of the left heart chambers. Timely diagnosis of IA in the pre-hemorrhagic period is problematic due to the variability of the clinical picture of IA, frequent blurred or low-symptomatic clinical course, the possibility of IA formation in the remote period after septic embolism, even despite the background of antibiotic therapy. The presented clinical case illustrates the first successful use of a low-profile flow-diverting stent for the treatment of a young patient with a mechanical heart valve and an infectious aneurysm of the left middle cerebral artery, developed at the site of septic embolism in the acute period of septic bacterial endocarditis accompanied by ischemic stroke. This observation demonstrates the effectiveness of the chosen method of treatment, peculiarities of adequate preoperative preparation, possible postoperative complications and detailed correction of anticoagulant and antiplatelet therapy.

Circulating Biomarkers in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy is the most common genetic heart disease. Biomarkers, molecules measurable in the blood, could inform the clinician by aiding in diagnosis, directing treatment, and predicting outcomes. We present an updated review of circulating biomarkers in hypertrophic cardiomyopathy representing key pathologic processes including wall stretch, myocardial necrosis, fibrosis, inflammation, hypertrophy, and endothelial dysfunction, in addition to their clinical significance.

Interleukin-27 Ameliorates Atherosclerosis in ApoE-/- Mice through Regulatory T Cell Augmentation and Dendritic Cell Tolerance.

Atherosclerosis, which is characterized by chronic inflammation in the arterial wall, is driven by immune cells and cytokines. Recent evidence indicated that interleukin (IL)-27 showed pleiotropic properties in immune diseases. However, precise mechanisms of IL-27, especially in atherosclerosis remains unknown. In our research, we examined the influence of the administration of IL-27 and an anti-IL-27p28 antibody (anti-IL-27p28-Ab) on both the initiation and the progression of atherosclerosis. In the groups (both the initiation and the progression) receiving recombinant IL-27 administration, the formation of atherosclerotic plaques was suspended, and the percentage of regulatory T cells (LAP+ or Foxp3+) in the spleen and peripheral blood was increased. Meanwhile, the number of T helper 1 (Th1) and T helper 17 (Th17) cells was decreased. In the peripheral blood plasma, TGF-β and IL-10 expression were increased, while the levels of IFN-γ and IL-17 were reduced. As for lesions, the mRNA expression of Foxp3, TGF-β, and IL-10 was increased, while that of IFN-γ and IL-17 was reduced. In the anti-IL-27p28 antibody groups, we obtained opposite results. We also observed that DCs treated with IL-27 display a tolerogenic phenotype and that IL-27-treated tolerogenic DCs (tDCs) are likely to play a protective role during atherosclerosis. Our study indicates that IL-27 or adoptive transfer of IL-27 loaded tDCs may be a new therapeutic approach in atherosclerosis.

Matr3 reshapes m6A modification complex to alleviate macrophage inflammation during atherosclerosis

Atherosclerosis, characterized as the chronic inflammation of the arterial wall, is one of the leading causes of coronary artery disease (CAD), and macrophages are found to play essential roles in the initiation and progression of inflammation in atherosclerosis. N6-methyladenosine (m6A) modification, as the most abundant epi-transcriptomic modification in mRNA, is found to mediate the atherogenic inflammatory cascades in vascular endothelium. The detailed molecular mechanism of m6A methylation regulating inflammatory response during atherosclerosis is still not fully known. In this study, we find oxidized low-density lipoprotein (oxLDL) stimulation increases methyltransferases Mettl3 and Mettl14 expressions in macrophages, whereas the total m6A modification level in macrophages decreases under oxLDL stimulation. Matrin-3 (Matr3), an RNA binding protein, is identified to play a suppressive role on oxLDL-mediated macrophage inflammatory responses through inhibiting activation of pro-inflammatory signaling, mitogen-activated protein kinase (Mapk) by m6A-mediated mRNA decay via regulating the formation of Mettl3-Mettl14 complex. Moreover, we find that Matr3 expression decreases in the oxLDL-stimulated macrophages, and the peripheral blood-derived monocytes from patients with CAD, and overexpression of Matr3 significantly alleviates atherosclerosis development in vivo. Our study for the first time clarifies the role of Matr3 on macrophage inflammatory responses during atherosclerotic development, and supplies deep understanding on the relationship of m6A modification and inflammatory responses in atherosclerosis.

Abstract 13700: LncRNA MERRICAL Controls Macrophage Chemotaxis and Vascular Inflammation by In-cis Regulation of CCL3/4 via H3k4me3 in Diabetes-Associated Atherosclerosis

Introduction: Diabetes-associated atherosclerosis is characterized by excessive vascular wall inflammation, including impaired lipid deposition, increased immune cell infiltration and plaque formation in the vessel wall. Macrophages are instrumental for lesion formation, however the mechanisms underlying their impaired functional capacity remain poorly understood in diabetes. Herein, we identify a unique role of a macrophage-enriched lncRNA MERRICAL (Macrophage Enriched lncRNA Regulates Inflammation, Chemotaxis, and AtheroscLerosis) in the development of diabetes-associated atherosclerosis. Methods: Transcriptomic analysis of the aortic intima from Ldlr -/- mice was performed at 4 time points along the continuum of lesion progression and regression under a high fat, high sucrose-containing (HFSC) or chow diet, respectively, to identify differentially expressed lncRNAs. Gain- and loss-of-function cell-based assays, RNA-protein interactions, and in vivo knockdown were performed to uncover the role of a top lncRNA candidate. Results: LncRNA MERRICAL is nuclear localized and increased by 249% in intimal lesions during progression. Transcriptomic analysis of MERRICAL -deficient bone marrow-derived macrophages showed decreased chemokine and inflammatory gene expression for Ccl3, Ccl4, and Il1β, with reduced chemotaxis and inflammatory-associated gene ontology pathways. Gain- and loss-of-function studies demonstrated the role of lncRNA MERRICAL in cis -regulation of its neighboring genes Ccl3 and Ccl4, an effect that is mediated in part via interaction with the histone modification enzyme H3K4me3. Remarkably, systemic knockdown of MERRICAL in HFSC-fed mice strongly reduced lesion formation by 73% in the aortic sinus by inhibiting the pro-inflammatory and Ccl3 - and Ccl4 -associated chemotactic response and decreasing the recruitment of leukocytes into the aortic wall. Conclusions: These findings establish a cis -regulatory mechanism by which a macrophage-specific lncRNA, MERRICAL , potently inhibits pro-inflammatory and chemotactic responses to alleviate lesion progression in diabetes, with implications for a broad range of diabetes-associated vascular disease states.

Abstract 11998: ADAR1 Mediates Macrophage Activation by Its Non-Editing Activity-Mediated Pri-miRNA Processing in Abdominal Aortic Aneurysm

Introduction: Macrophage activation plays a critical role in abdominal aortic aneurysm (AAA) development. However, molecular mechanisms controlling macrophage activation in AAA remain largely unknown. The objective of the study was to identify novel mechanisms underlying adenosine deaminase acting on RNA (ADAR1) function in macrophage activation and AAA formation. Methods: Aortic transplantation was conducted to determine the importance of non-vascular ADAR1 in AAA development. Angiotensin II (Ang II) infusion of ApoE–/– mouse combined with macrophage-specific knockout of ADAR1 was used to study ADAR1 macrophage-specific role in AAA formation. Primary cultured bone-marrow derived and peritoneal macrophages were used to study how ADAR1 regulates macrophage activation. Moreover, a novel humanized AAA model was established by transplanting human artery to immunodeficient mouse aorta followed by immunity reconstitution with ADAR1-deficient human monocytes to test the role of human macrophages in aneurysm formation in human arteries. Results: Allograft transplantation of wild type abdominal aortas to ADAR1+/- recipient mice significantly attenuated AAA formation, suggesting that non-vascular ADAR1 is essential for AAA development. ADAR1 deficiency in hematopoietic cells decreased the prevalence of AAA while inhibited macrophage infiltration and aorta wall inflammation. ADAR1 deletion blocked the classic macrophage activation, diminished NF-κB signaling, and enhanced the expression of many anti-inflammatory miRNAs. Mechanistically, ADAR1 interacted with Drosha to promote its degradation, which attenuated Drosha-DGCR8 interaction, and consequently inhibited pri- to pre-miRNA processing of miRNAs targeting IKKβ, resulting in an increased IKKβ expression and enhanced NF-κB signaling. Reconstitution of ADAR1-deficient, but not the wild type, human monocytes to immunodeficient mice blocked the aneurysm formation in transplanted human arteries. Conclusions: Macrophage ADAR1 promotes AAA formation in both mouse and human arteries through a novel mechanism, i.e., Drosha protein degradation, which inhibits the processing of miRNAs targeting NF-kB signaling and thus elicits macrophage-mediated vascular inflammation.

JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm

JAK2V617F mutation is associated with an increased risk for athero-thrombotic cardiovascular disease, but its role in aortic disease development and complications remains unknown. In a cohort of patients with myeloproliferative neoplasm, JAK2V617F mutation was identified as an independent risk factor for dilation of both the ascending and descending thoracic aorta. Using single-cell RNA-seq, complementary genetically-modified mouse models, as well as pharmacological approaches, we found that JAK2V617F mutation was associated with a pathogenic pro-inflammatory phenotype of perivascular tissue-resident macrophages, which promoted deleterious aortic wall remodeling at early stages, and dissecting aneurysm through the recruitment of circulating monocytes at later stages. Finally, genetic manipulation of tissue-resident macrophages, or treatment with a Jak2 inhibitor, ruxolitinib, mitigated aortic wall inflammation and reduced aortic dilation and rupture. Overall, JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm.

EOSINOPHILIC MYENTERIC GANGLIONITIS: A RARE CAUSE OF GASTROINTESTINAL DYSMOTILITY

<h3>Introduction</h3> Eosinophilic myenteric ganglionitis is a rare inflammatory neuropathy characterized by infiltration of eosinophils in the myenteric plexus, often presenting with pseudo-obstruction. It is likely an under-recognized cause of enteric motility disorders with an allergic component. <h3>Case Description</h3> A 32-year-old female with chronic abdominal pain associated with diarrhea, vomiting, and weight loss was admitted for acute worsening of symptoms. Exacerbations are accompanied by syncope/near-syncope, flushing, anxiety, palpitations, diaphoresis, and mouth numbness. She denied angioedema, shortness of breath, urticaria. Ex-laparotomy was performed to alleviate obstruction along with resection of "unhealthy bowel." Surgical pathology with C-kit immunostaining showed prominent mast cells and eosinophils in the muscularis propria, myenteric plexus, and submucosa with atrophy and fibrosis of the small bowel. There were also intraganglionic (1-8/ganglion) and periganglionic eosinophils (>20) observed in the myenteric plexus. Colon pathology was unremarkable. She had peripheral eosinophilia of 310 cells/μl and tryptase level of 5.1/L.KIT (D816V) mutation was negative. Urinary N-Methylhistamine collected over 24 hours was 282 mcg/g of creatinine. The patient was started on antihistamines as prophylaxis for a possible mast cell syndrome. <h3>Discussion</h3> This patient's history and clinical findings are consistent with a rare diagnosis of eosinophilic myenteric ganglionitis along with possible mast cell disorder. The main findings of inflammation of muscle wall with eosinophils, lymphocytes, and markedly increased mast cells raise the possibility of mast cell-related dysmotility causing her SBO. These findings have rarely been reported in the literature. The patient could possibly benefit from treatment with an IL4 or IL-5 receptor antagonist.

A Mysterious Case of Abdominal Pain

A Mysterious Case of Abdominal Pain

Study of the JAK inhibitors antifibrotic activity for the prevention and treatment of chronic thromboembolic pulmonary hypertension

Introduction. Chronic thromboembolic pulmonary hypertension (CTEPH) is the most common complication of pulmonary thromboembolism (PE). Fibrous remodeling of the pulmonary circulation vessels against the background of CTEPH leads to an irreversible increase of the vessel wall stiffness and the ineffectiveness of CTEPH treatment. The involvement of Janus kinase (JAK) in the regulation of vascular wall and lung tissue inflammation and fibrosis allows for the possible effectiveness of JAK 1,2 inhibitors (iJAK) in the course of CTEPH. Purpose – to study the antifibrotic effect of iJAK for the prevention and treatment of CTEPH. Materials and methods. The study was conducted on male Wistar rats. Modeling of CTEPH was performed by sequential embolization of the vascular bed with partially biodegradable sodium alginate microspheres. 2 weeks after the last administration of the microspheres, low, medium and high doses of iJAK were initiated. To assess the effectiveness of the substance, the following tests were used: treadmill test, echocardiography, cardiac catheterization with right ventricular (RV) manometry, histological examination of the lungs. Results. Animals undergone vascular embolization demonstrated decreased exercise tolerance at all observation points compared to healthy animals. The placebo group, in contrast with the group getting treatment and iJAK, was found to have an increased mean RV pressure compared to healthy animals. There was an increase in mean RV pressure in the placebo group (15.5±7.7 mmHg) and in the low dose and iJAK group (13.4±6.4 mmHg) compared with healthy animals (9.4±2.2 mmHg). Vascular hypertrophy of the pulmonary artery branches was lower in group getting average dosages and iJAK compared with the placebo group (54.9±19.0 and 68.9±23.1 %, respectively). Thus, the suppression by iJAK of aseptic inflammation and following fibrosis leads to the decreasing of severity of pulmonary circulation remodeling in the experimental model of CTEPH. This approach can be used in the comprehensive bypass and prevention of CTEPH.

Relationship between histopathological features of non-infectious aortitis and the results of pre-operative 18F-FDG-PET/CT: a retrospective study of 16 patients.

To describe the characteristics of 18F-fluorodeoxyglucose positron-emission tomography/computed-tomography (18FDG-PET/CT) findings before surgery in patients with active, histologically confirmed aortitis, and to correlate the degree of arterial wall inflammation with PETVAS score. This was a multiple-centre retrospective study including cases with histologically proven active, non-infectious aortitis who had a 18FDG-PET/CT performed within one year before surgery for aneurysm repair. PETVAS score was determined by radiologists blinded to the pathology findings. Cardiovascular pathologists reviewed aortic tissue samples and graded the degree of inflammation in the vessel wall. Sixteen patients were included (8 giant cell arteritis, 4 clinically isolated aortitis, 2 Takayasu's arteritis, 1 relapsing polychondritis, and 1 rheumatoid arthritis). In 5/16 (31%) patients, 18FDG-PET/CT did not detect the presence of aortic inflammation; two of whom were being treated with glucocorticoids at the time of procedure. Ascending thoracic and abdominal aorta had the highest FDG uptake among the affected territories. Patients without active aortitis on 18FDG-PET/CT were significantly older (p=0.027), had a lower PETVAS score (p=0.007), and had a lower degree of adventitial inflammation (p=0.035). In contrast, there was no difference between 18FDG-PET/CT active and inactive aortitis patients as regards the timing between PET/CT and surgery, serum CRP level (during 18FDG-PET/CT) and, FDG uptake per study site. In histologically proved aortitis, 18FDG-PET/CT before surgery did not detect vascular inflammation in 31% patients, and PETVAS score correlated with the degree of adventitial histopathologic inflammation.

Macrophage-specific deletion of neuropilin-2 inhibits inflammatory signalling and attenuates atherosclerotic plaque development in apolipoprotein e-deficient mice

Abstract Background Atherosclerosis is the underlying pathology in most cases of ischaemic heart disease, which itself remains the leading cause of mortality worldwide. Atherosclerosis is a multifaceted vascular disease characterised by arterial wall inflammation resulting from the subendothelial retention, and modification, of lipoproteins by macrophages. Macrophages exhibit a high degree of plasticity, and undergo polarisation to a pro-inflammatory phenotype in response to pro-inflammatory cytokines and other environmental stimuli, making them an attractive therapeutic target. Neuropilin-2 (NRP2) is a cell-surface co-receptor with essential roles in angiogenesis and axonal guidance, and is also expressed by macrophages. However, little is known about the role of NRP2 in macrophage function or atherosclerosis. Purpose To investigate whether NRP2 is important for macrophage involvement in atherosclerosis, we characterised the effects of conditional NRP2 deletion on macrophage function and atherosclerotic plaque development. Methods We generated mice with macrophage-specific (LysM-Cre) deletion of Nrp2, and lineage tracing via EYFP transgene expression, on the pro-atherogenic Apolipoprotein E-deficient background (Nrp2-KOMac, Apoe−/−, EYFP). These mice were fed a high-fat diet (HFD) for 16 weeks before their aortas were stained with Oil-red-O to assess plaque coverage. Plaque content was then characterised by sectioning and staining the aortic roots. The role of NRP2 in modulating pro-inflammatory macrophage polarisation and signalling, was assessed using functional assays and transcriptome analysis in Nrp2-KO bone marrow-derived macrophages (BMDMs). Results HFD-induced plaque development was significantly reduced in Nrp2-KOMac, Apoe−/−, EYFP mice, with 17.4% total aortic plaque coverage in Nrp2-KOMac, Apoe−/−, EYFP mice, compared to 24.9% in WTApoe−/−, EYFP mice (p=0.0021, n=10). Plaques from Nrp2-KOMac, Apoe−/−, EYFP mice also displayed features consistent with increased plaque stability, including reduced necrotic core area and plaque lipid content, and increased cap thickness. NRP2 was significantly upregulated upon M-CSF-mediated differentiation of bone marrow progenitors into BMDMs, and further upregulated by pro-inflammatory polarisation using LPS and IFN-gamma. Furthermore, upregulation of Il1β, Tnfα and Il6, induced by LPS and IFN-gamma, was significantly reduced in Nrp2-KO BMDMs, and MCP-1 induced migration was also decreased in these cells. Transcriptome analysis revealed that NF-kappaB signalling pathway genes, and genes regulating monocyte chemotaxis, were downregulated in Nrp2-KO BMDMs. Conclusion Macrophage-derived NRP2 is pro-atherogenic, likely resulting from its role in positively regulating pro-inflammatory signalling and macrophage migration. Targeting NRP2 expressed on the surface of macrophages could therefore offer a novel therapeutic approach for reducing the disease burden associated with atherosclerosis. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation (MB PhD Studentship)

Neuroimaging evaluation of unilateral asymptomatic carotid plaque ulceration: preliminary results of the Carotid Artery Multimodality imaging Prognostic study

Abstract Background Carotid plaque ulceration has been associated with imaging characteristics of high risk of future events (plaque vulnerability) in patients with a significant degree of stenosis, while little is known about its role in patients with a lesser degree of stenosis and its association with markers of vascular inflammation. Purpose We evaluated the association between imaging characteristics of plaque vulnerability and vascular inflammation detected by different imaging tests. Methods One hundred and seven patients with unilateral asymptomatic carotid artery stenosis (40–60% detected by Doppler ultrasound (DUS)), enrolled in the ongoing Carotid Artery Multimodality Prognostic (CAMP) study were prospectively evaluated with computed tomography angiography (CTA), contrast-enhanced magnetic resonance imaging (CEMRA) and, in a subgroup of patients, with 18-F-fluorodeoxyglucose positron emission tomography (PET). Plaque ulceration was detected by CTA. Variables are expressed as median (1st–3rd quartiles) and number (percentages).The Student's t-test or Mann-Whitney and Chi square or Fisher's exact test were used to study associations among variables. Results An ulcerated plaque was present in 35% patients (n=33) of those undergoing CTA (n=94), while intraplaque hemorrhage and lipid-rich necrotic core were present in 9% and 15% of those undergoing CEMRA. Compared with patients with non-ulcerated plaques, those with an ulcerated plaque had a significant higher degree of stenosis at DUS, a higher target to background ratio (TBR) at 18F-FDG-PET and a higher high-sensitivity cardiac troponin (cTn) T. Conclusions Plaque ulceration is common and associated with higher degree of stenosis, higher indices of wall inflammation and higher serum markers of myocardial injury. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Regione Toscana

Effect of Particulate Matter on Achilles Tendon Healing: An Experimental Study in Rats

Category: Basic Sciences/Biologics; Ankle; Sports; Trauma Introduction/Purpose: Exposure of particulate matter (PM) has been linked to several diseases including pulmonary, cardiovascular, oncology, neurology system, and etc. Even though tendon injury has become increasingly common recently, there has been no study of relationship between tendon healing and PM. Hence, we performed experimental study in rats to evaluate whether PM has significant effect on tendon healing. We hypothesized that PM exposure may substantially influence Achilles tendon healing. Here, we evaluated whether PM exposure led to deleterious effect on tendon healing in a rat model of Achilles tendon rupture (ATR). Methods: All experiments with rats were approved by the Institutional Animal Care and Use Committee. The Achilles tendons of 20 Sprague-Dawley rats were transected by open tenotomy. The animals were divided into two groups according to exposure of PM 2.5 (particulate matter less than 2.5µm): control group (Non-PM group) or PM exposure group (PM group). 30 minutes of PM inhalational exposure was performed 3 days a week for 6 weeks in closed chamber systems. After 6 weeks, histologic study of lung, laboratory test and enzyme-linked immunosorbent assay (ELISA) of blood samples, histologic study, transmission electron microscopy (TEM) analysis, biomechanical study, RNA sequencing, and western blot analysis of Achilles tendon was performed. Results: Hematoxylin and eosin (H&amp;E) stain of lung tissue in PM group showed inflammation of alveolar wall and increased macrophage. Laboratory test and ELISA of blood samples from PM group showed significantly higher expression of white blood cell count and tissue necrosis factor alpha (TNF-α) than those from non-PM group, respectively. Histologic study of Achilles tendon in PM group exhibited increased lymphocyte and ossification findings with inflammatory change of cell morphology. TEM analysis showed decreased collagen fibril in PM group than non-PM group. Load to failure was decreased in the PM group than non-PM group. RNA sequencing and ingenuity pathway analysis showed increased cAMP-PKA-CREB signal pathway in PM group and the results were consistent with western blot outcomes. Conclusion: Achilles tendon healing was substantially affected by the PM exposure. Based on the present data, PM exposure induces detrimental histological and biomechanical results on Achilles tendon healing through cAMP-PKA-CREB pathway. Further in-vitro study and larger in-vivo study with longer time period are needed to support the present data.

S2055 Intra-Diverticular Polyp Associated With Acute Diverticulitis

Introduction: The incidence of both colon polyps and diverticulosis increases with age. Intra-diverticular polyps are a very rare findings despite the relatively high prevalence of both colon polyps and diverticulosis. Acute diverticulitis happens in approximately 5-10% of patients with diverticulosis. Risk factors for acute diverticulitis have been well described including age, NSAIDs, and dietary factors. There is limited evidence on the incidence of diverticulitis associated with colon polyps. Case Description/Methods: A 44-year-old woman with no significant medical history was referred for evaluation after a recent episode of acute uncomplicated diverticulitis confirmed on CT. She was treated with a short course of antibiotics in the outpatient setting. The patient had a normal BMI and was not using any NSAIDs previously. The patient subsequently underwent a diagnostic colonoscopy and was found to have sigmoid diverticulosis. A single 5 mm semi-pedunculated polyp was found arising from the base of a diverticulum (Figure). The polyp was resected using forceps to evert the diverticulum and fully visualize the polyp. Histologic examination revealed an inflammatory polyp. Discussion: Here we present a case of a patient who was found to have an intra-diverticular polyp after an episode of acute diverticulitis. The patient had no other risk factors for acute diverticulitis which suggests the polyp may have been the underlying cause of the diverticulitis. Intra-diverticular polyps are rare. To the best of our knowledge, diverticulitis caused by such polyps is exceedingly rare. Polyp location or growth in the diverticulum may led to obstruction, inflammation or erosion of the thin diverticular wall. Because the polyp was inflammatory, we cannot rule out the possibility that it may have developed after the episode. Whether the polyp was the trigger or the result of diverticulitis, this rare association highlights the importance of a colonoscopy after an episode of acute diverticulitis to rule out other pathology.Figure 1.: Left: Intra-diverticular polyp. Right: Forceps were used to fully visualize and resect the polyp.

Trehalose-induced alterations in serum expression levels of microRNAs associated with vascular inflammation in patients with coronary artery disease - the pilot results from the randomized controlled trial.

IntroductionBackground: This study aimed to investigate the trehalose-induced alterations in serum expression levels of miRNAs associated with vascular inflammation in patients with coronary artery disease (CAD) in order to evaluate the effectiveness of intravenous (IV) trehalose administration in reducing arterial wall inflammation.Material and methodsMethods: This trial enrolled 14 men with a history of myocardial infarction (MI) and systemic inflammation. The patients were randomized in a 2:1 ratio to trehalose (15g/week, IV administration) (N=10) or placebo (equal volume 0.9% normal saline) (N=4) for a period of 12-weeks. The relative serum expression levels of miRNA-126, miRNA-24, miRNA-181b, miRNA-10a and miRNA-92a were assessed.ResultsResults: IV trehalose administration significantly increased the serum level of miRNA-24 (2.473±0.72; P=0.037) compared to the baseline, but did not alter the other miRNA serum levels. However, at the end of the study, miRNA-24 (4.58±0.99; P=0.002), miRNA-181b (4.08±1.75; P=0.009) and miRNA-10a (3.68±0.63; P=0.013) showed notably higher serum levels in the trehalose relative to the placebo group. Furthermore, the reduction (normalized to baseline) in serum levels of miRNA-126 (P=0.042) and miRNA-92a (P=0.001) were reduced in the trehalose versus placebo group, while the serum level of miRNA-24 (P=0.007) was notably higher than that in the placebo group.ConclusionsConclusion: Serum levels of miRNAs associated with vascular inflammation were altered following IV trehalose administration. The alterations in serum miRNAs, especially miRNA-126 and miRNA-24, could be considered as helpful biomarkers for the evaluation of trehalose potency in reducing arterial wall inflammation in patients with CAD.

Experimental study of a heparin-coated venous stent fabricated by atomic layer deposition.

To evaluate the safety and efficacy of heparin-coated venous stents in animals. We used atomic layer deposition technology to obtain a heparin coating with good stability and then prepared a heparin-coated venous stent based on this technology. The experimental stents were prepared according to the diameter of the rabbit inferior vena cava and were divided into Ni-Ti alloy stent group, Ni-Ti-Al2O3 stent group and Ni-Ti-Al2O3-Heparin stent group. 3 days, 7 days and 14 days after stent implantation, the materials were collected, and the three groups of stents were observed by hard tissue section pathology, immunohistochemistry and scanning electron microscope to observe the differences in vascular wall inflammation, thrombosis, lumen stenosis and vascular intima regeneration. The experiment confirmed the safety of the heparin-coated stent in vivo. Compared with the control group, the experimental group showed a high degree of vascular endothelialization and an intact neointimal structure 14 days after implantation. The long-term safety and biological effects of heparin-coated venous stents in animals require further study.

Irisin inhibits PCSK9 expression through activating AMPK-SREBP2 pathway

AimsPrevious studies found that irisin attenuated the vascular wall inflammation caused by Oxidized low-density lipoprotein (ox-LDL), and recent experiments have shown that proprotein convertase subtilisin/kexin type 9 (PCSK9) can act on various cells in the vascular wall to induce inflammatory responses. But, the relationship between irisin and PCSK9 has not been reported. The aim of this study was to investigate the effect of irisin on PSCK9 in endothelial cells and hepatocytes under the induction of ox-LDL. MethodsExperiments were performed using human umbilical vein endothelial cells and Hep G2, and cells were treated with irisin and (or) ox-LDL for evaluating expression of PCSK9 and downstream inflammatory proteins, while the expression levels of AMP-dependent protein kinase (AMPK) and sterol-regulatory element binding protein 2 (SREBP2) were also examined. Then Compound C was used to inhibit AMPK activation and SiAMPK for silencing of AMPK mRNA, and the above assays were also performed to deeply validate the role of the AMPK-SREBP2 pathway. ResultsIrisin treatment significantly downregulated the expression of PCSK9 and inflammation-related proteins induced by ox-LDL, also restored the content of p-AMPK and reduced the SREBP2 content. After the use of Compound C or SiAMPK, the content of p-AMPK was obviously decreased, and the positive effect of irisin was greatly weakened. ConclusionsThis study demonstrates that irisin suppresses PCSK9 expression through the AMPK-SREBP2 pathway and ameliorates ox-LDL-induced endothelial cells inflammation.

Atherosclerosis Burdens in Diabetes Mellitus: Assessment by PET Imaging.

Arteriosclerosis and its sequelae are the most common cause of death in diabetic patients and one of the reasons why diabetes has entered the top 10 causes of death worldwide, fatalities having doubled since 2000. The literature in the field claims almost unanimously that arteriosclerosis is more frequent or develops more rapidly in diabetic than non-diabetic subjects, and that the disease is caused by arterial inflammation, the control of which should therefore be the goal of therapeutic efforts. These views are mostly based on indirect methodologies, including studies of artery wall thickness or stiffness, or on conventional CT-based imaging used to demonstrate tissue changes occurring late in the disease process. In contrast, imaging with positron emission tomography and computed tomography (PET/CT) applying the tracers 18F-fluorodeoxyglucose (FDG) or 18F-sodium fluoride (NaF) mirrors arterial wall inflammation and microcalcification, respectively, early in the course of the disease, potentially enabling in vivo insight into molecular processes. The present review provides an overview of the literature from the more than 20 and 10 years, respectively, that these two tracers have been used for the study of atherosclerosis, with emphasis on what new information they have provided in relation to diabetes and which questions remain insufficiently elucidated.