Wall Inflammation Research Articles

Endothelial Damage Arising From High Salt Hypertension Is Elucidated by Vascular Bed Systematic Profiling.

Considerable evidence links dietary salt intake with the development of hypertension, left ventricular hypertrophy, and increased risk of stroke and coronary heart disease. Despite extensive epidemiological and basic science interrogation of the relationship between high salt (HS) intake and blood pressure, it remains unclear how HS impacts endothelial cell (EC) and vascular structure in vivo. This study aims to elucidate HS-induced vascular pathology using a differential systemic decellularization in vivo approach. We performed systematic molecular characterization of the endothelial glycocalyx and EC proteomes in mice with HS (8%) diet-induced hypertension versus healthy control animals. Isolation of eGC and EC compartments was achieved using differential systemic decellularization in vivo methodology. Altered protein expression in hypertensive compared to normal mice was characterized by liquid chromatography tandem mass spectrometry. Proteomic results were validated using functional assays, microscopic imaging, and histopathologic evaluation. Proteomic analysis revealed a significant downregulation of eGC and associated proteins in HS diet-induced hypertensive mice (among 1696 proteins identified in this group, 723 were markedly decreased in abundance, while only 168 were increased in abundance. Bioinformatic analysis indicated substantial derangement of the eGC layer, which was subsequently confirmed by fluorescent and electron microscopy assessment of vessel damage ex vivo. In the EC fraction, HS-induced hypertension significantly altered protein mediators of contractility, metabolism, mechanotransduction, renal function, and the coagulation cascade. In particular, we observed dysregulation of integrin subunits α2, α2b, and α5, which was associated with arterial wall inflammation and substantial infiltration of CD68+ monocyte-macrophages. Consequently, HS-induced hypertensive mice also displayed reduced vascular integrity of multiple organs including lungs, kidneys, and heart. These findings provide novel molecular insight into HS-induced structural changes in eGC and EC composition that may increase cardiovascular risk and potentially guide the development of new diagnostics and therapeutic interventions.

ADAR1 Non-Editing Function in Macrophage Activation and Abdominal Aortic Aneurysm.

Macrophage activation plays a critical role in abdominal aortic aneurysm (AAA) development. However, molecular mechanisms controlling macrophage activation and vascular inflammation 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. Aortic transplantation was conducted to determine the importance of nonvascular ADAR1 in AAA development/dissection. Ang II (Angiotensin II) infusion of ApoE-/- mouse model combined with macrophage-specific knockout of ADAR1 was used to study ADAR1 macrophage-specific role in AAA formation/dissection. The relevance of macrophage ADAR1 to human AAA was examined using human aneurysm specimens. Moreover, a novel humanized AAA model was established to test the role of human macrophages in aneurysm formation in human arteries. Allograft transplantation of wild-type abdominal aortas to ADAR1+/- recipient mice significantly attenuated AAA formation, suggesting that nonvascular ADAR1 is essential for AAA development. ADAR1 deficiency in hematopoietic cells decreased the prevalence and severity of AAA while inhibited macrophage infiltration and aorta wall inflammation. ADAR1 deletion blocked the classic macrophage activation, diminished NF-κB (nuclear factor kappa B) signaling, and enhanced the expression of a number of anti-inflammatory microRNAs. Mechanistically, ADAR1 interacted with Drosha to promote its degradation, which attenuated Drosha-DGCR8 (DiGeorge syndrome critical region 8) interaction, and consequently inhibited pri- to pre-microRNA processing of microRNAs targeting IKKβ, resulting in an increased IKKβ (inhibitor of nuclear factor kappa-B) expression and enhanced NF-κB signaling. Significantly, ADAR1 was induced in macrophages and interacted with Drosha in human AAA lesions. Reconstitution of ADAR1-deficient, but not the wild type, human monocytes to immunodeficient mice blocked the aneurysm formation in transplanted human arteries. Macrophage ADAR1 promotes aneurysm formation in both mouse and human arteries through a novel mechanism, that is, Drosha protein degradation, which inhibits the processing of microRNAs targeting NF-kB signaling and thus elicits macrophage-mediated vascular inflammation in AAA.

Immunology of Giant Cell Arteritis.

Giant cell arteritis is an autoimmune disease of medium and large arteries, characterized by granulomatous inflammation of the three-layered vessel wall that results in vaso-occlusion, wall dissection, and aneurysm formation. The immunopathogenesis of giant cell arteritis is an accumulative process in which a prolonged asymptomatic period is followed by uncontrolled innate immunity, a breakdown in self-tolerance, the transition of autoimmunity from the periphery into the vessel wall and, eventually, the progressive evolution of vessel wall inflammation. Each of the steps in pathogenesis corresponds to specific immuno-phenotypes that provide mechanistic insights into how the immune system attacks and damages blood vessels. Clinically evident disease begins with inappropriate activation of myeloid cells triggering the release of hepatic acute phase proteins and inducing extravascular manifestations, such as muscle pains and stiffness diagnosed as polymyalgia rheumatica. Loss of self-tolerance in the adaptive immune system is linked to aberrant signaling in the NOTCH pathway, leading to expansion of NOTCH1+CD4+ T cells and the functional decline of NOTCH4+ T regulatory cells (Checkpoint 1). A defect in the endothelial cell barrier of adventitial vasa vasorum networks marks Checkpoint 2; the invasion of monocytes, macrophages and T cells into the arterial wall. Due to the failure of the immuno-inhibitory PD-1 (programmed cell death protein 1)/PD-L1 (programmed cell death ligand 1) pathway, wall-infiltrating immune cells arrive in a permissive tissues microenvironment, where multiple T cell effector lineages thrive, shift toward high glycolytic activity, and support the development of tissue-damaging macrophages, including multinucleated giant cells (Checkpoint 3). Eventually, the vascular lesions are occupied by self-renewing T cells that provide autonomy to the disease process and limit the therapeutic effectiveness of currently used immunosuppressants. The multi-step process deviating protective to pathogenic immunity offers an array of interception points that provide opportunities for the prevention and therapeutic management of this devastating autoimmune disease.

Clearance of Stress-Induced Premature Senescent Cells Alleviates the Formation of Abdominal Aortic Aneurysms.

Abdominal aortic aneurysm (AAA) is a multifactorial disease characterized by various pathophysiological processes, including chronic inflammation, oxidative stress, and proteolytic activity in the aortic wall. Stress-induced premature senescence (SIPS) has been implicated in regulating these pathophysiological processes, but whether SIPS contributes to AAA formation remains unknown. Here, we detected SIPS in AAA from patients and young mice. The senolytic agent ABT263 prevented AAA development by inhibiting SIPS. Additionally, SIPS promoted the transformation of vascular smooth muscle cells (VSMCs) from a contractile phenotype to a synthetic phenotype, whereas inhibition of SIPS by the senolytic drug ABT263 suppressed VSMC phenotypic switching. RNA sequencing and single-cell RNA sequencing analysis revealed that fibroblast growth factor 9 (FGF9), secreted by stress-induced premature senescent VSMCs, was a key regulator of VSMC phenotypic switching and that FGF9 knockdown abolished this effect. We further showed that the FGF9 level was critical for the activation of PDGFRβ/ERK1/2 signaling, facilitating VSMC phenotypic change. Taken together, our findings demonstrated that SIPS is critical for VSMC phenotypic switching through the activation of FGF9/PDGFRβ/ERK1/2 signaling, promoting AAA development and progression. Thus, targeting SIPS with the senolytic agent ABT263 may be a valuable therapeutic strategy for the prevention or treatment of AAA.

Морфофункциональное состояние эндотелия сосудов в периферических нервах овец при патологии

In a comparative aspect, studies of experimental models of hepatosis in sheep, depending on etiological factors, were carried out. Comprehensive studies made it possible to characterize the morphofunctional state of the peripheral nervous system in sheep and the vascular endothelium. With prolonged exposure to various damaging factors, there is a gradual depletion of compensatory capabilities in the peripheral nervous system and the endothelial cover of the vessels, which leads to an increase in exudative activity, respectively, and vasoconstriction. the relaxing and constrictor functions of the endothelium are disturbed, as well as the production of anticoagulant and procoagulant substances, growth factors and their inhibitors, etc. It has been established that due to the commonality of innervation, blood circulation of the abdominal organs in pathology, a combined pathology develops, which is manifested by the corresponding syndromes. In this regard, pathogenetic mechanisms of dysfunction of myelinated and unmyelinated nerve fibers and vascular endothelium have been established. Endothelial dysfunction occurs with an imbalance in the synthesis of endothelins, bradykinin, eicosanoids, NO, inactivation of acetylcholine, catecholamines, serotonin, histamine, etc. The vascular intima ceases to perform barrier, secretory, hemostatic, vasotonic functions, reducing its role in the processes of inflammation and remodeling of the vascular wall. Trophic function disorders are manifested by morphological changes in the peripheral nervous system. In myelinated and unmyelinated nerve fibers, dystrophic processes are induced that do not bypass neurolemmocytes and connective tissue.

Pathogenesis of Fistulating Crohn's Disease: A Review.

Sustained, transmural inflammation of the bowel wall may result in the development of a fistula in Crohn's disease (CD). Fistula formation is a recognized complication and cause of morbidity, occurring in 40% of patients with CD. Despite advanced treatment, one-third of patients experience recurrent fistulae. Development of targeting treatment for fistulae will be dependent on a more in depth understanding of its pathogenesis. Presently, pathogenesis of CD-associated fistulae remains poorly defined, in part due to the lack of accepted invitro tissue models recapitulating the pathogenic cellular lesions linked to fistulae and limited invivo models. This review provides a synthesis of the existing knowledge of the histopathological, immune, cellular, genetic, and microbial contributions to the pathogenesis of CD-associated fistulae including the widely accredited contribution of epithelial-to-mesenchymal transition, upregulation of matrix metalloproteinases, and overexpression of invasive molecules, resulting in tissue remodeling and subsequent fistula formation. We conclude by exploring how we might utilize advancing technologies to verify and broaden our current understanding while exploring novel causal pathways to provide further inroads to future therapeutic targets.

Uticaj polifenola na razvoj ateroskleroze

Polyphenols represent one of the biggest and most widespread groups of secondary plant metabolites with more than 8000 polyphenolic compounds. Fruits, vegetables and beverages such as tea and red wine are the main sources of polyphenols. A significant number of studies indicate the ability of certain polyphenols to delay the development of atherosclerosis. According to the same polyphenols reduce lipid deposition, oxidative stress, inflammation of the blood vessel wall, proliferation of vascular smooth muscle cells and endothelial dysfunction. The widespread use of polyphenols requires further research on bioavailability, absorption and transformation. It is necessary to determine the effect of individual polyphenols as well as the interaction with other bioactive compounds, define the dietary reference intake and the safety of use in certain subpopulations.

Frequency of Preneoplastic and Neoplastic Lesions in Cholecystectomy Specimen from a Tertiary Care Hospital in Uttar Pradesh, India: A Cross-sectional Study

Introduction: Cholelithiasis is known to cause a spectrum of changes, including inflammation in the gallbladder wall, cholesterolosis, atrophy, metaplasia, dysplasia, polyps, and eventually cancer. Gallbladder Carcinoma (GBC) is a rare and highly fatal malignancy. Aim: To determine the frequency of preneoplastic and neoplastic lesions, along with demographic and clinical aspects of different gallbladder lesions. Materials and Methods: This cross-sectional study was performed on 788 patients who underwent elective cholecystectomy for gallbladder disease at Hind Medical College, Sitapur, Uttar Pradesh, India, from August 2017 to October 2021. All patients underwent a history and physical examination, followed by routine laboratory tests and other investigations, including full abdominal ultrasound. Histopathologic evaluation of the gallbladder specimen was also performed after surgical resection. Categorical variables were presented as numbers and percentages (%), while continuous variables were presented as mean ± Standard Deviation (SD). Results: A total of 788 cholecystectomy specimens were analysed. The mean age of the patients was 42.49±1.39 years with female predominance 640 (82.05%). The majority of cases were between 40-49 269 (34.13%) and 60-69 399 (50.63) years of age. Preneoplastic changes were found in 764 (96.96%) cases, while neoplastic pathology was evident in 24 (3.04%) cholecystectomy specimens. The most commonly observed preneoplastic change was chronic cholecystitis in 532 (67.54%) cases. Other lesions associated with chronic cholecystitis were cholesterolosis in 76 cases (9.64%), xanthogranulomatous cholecystitis in 34 cases (4.31%), follicular cholecystitis in 30 cases (3.80%), and GBC in 24 cases (3.04%). Conclusion: This study observed that chronic cholecystitis and cholesterolosis, followed by xanthogranulomatous cholecystitis, were associated with metaplastic changes in gallbladder pathologies. It is believed that metaplasia-dysplasia could be linked to GBC. Therefore, routine microscopic examination is required for all cholecystectomies. However, further studies on gallbladder carcinogenesis are needed.

Extract of Laurus nobilis attenuates inflammation and epithelial ulcerations in an experimental model of inflammatory bowel disease

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are classified as chronic inflammatory disorders and typically require anti-inflammatory drug therapies, such as glucocorticoid regimens, non-steroidal anti-inflammatory drugs, and biologics, aimed at reducing inflammation in the bowel wall. However, each of these therapies is accompanied by a list of possible serious side effects. Because of this, there remains an urgent need to identify new pharmacologic options to reduce or prevent the pro-inflammatory events of IBD while minimizing adverse side effects, and to make available more cost-effective treatment modalities. We have previously identified several herbal extracts that demonstrate potent bio-inhibitory activity of the innate immune response. In particular, Laurus nobilis (LN), or more commonly called bay laurel, demonstrated significant anti-inflammatory function by inhibiting nuclear factor-κB activation. Based upon our original in vitro findings, we have now examined the effects of this herbal extract on a murine dextran sodium sulfate (DSS) model of IBD. Hematoxylin and eosin-stained paraffin sections prepared from DSS treated animals show clear epithelial damage, including ulcerations, extensive neutrophil infiltration into the mucosal layer, and granuloma formation. Tissue from DSS treated animals that also received LN extract showed improved tissue morphology more closely resembling that from control animals. In addition, DSS treated mice with co-administration of LN extract showed a significant reduction in CD4+ antibody staining within the mucosal layer in colonic sections indicating reduced lymphocyte infiltration. Based on these findings, we believe that administration of LN extracts may be effective in reducing the intestinal epithelial damage seen in human IBD and warrants further investigation through clinical trials. Lay Summary: Inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), manifest as chronic inflammation and ulceration of tissues lining the digestive tract. CD involves inflammation of the deeper layers of the digestive tract, including both the small and large intestines, and less commonly, the upper digestive tract. UC involves inflammation along the lining of the colon and rectum. Steroid or biologic treatments for IBD are common, however, are limited due to significant side effects and/or prohibitive cost. In the present study, we provide evidence for use of the natural product, Laurus nobilis (bay leaf), as a safe and effective anti-inflammatory therapy for IBD.

Extract of Laurus nobilis attenuates inflammation and epithelial ulcerations in an experimental model of inflammatory bowel disease

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are classified as chronic inflammatory disorders and typically require anti-inflammatory drug therapies, such as glucocorticoid regimens, non-steroidal anti-inflammatory drugs, and biologics, aimed at reducing inflammation in the bowel wall. However, each of these therapies is accompanied by a list of possible serious side effects. Because of this, there remains an urgent need to identify new pharmacologic options to reduce or prevent the pro-inflammatory events of IBD while minimizing adverse side effects and making available more cost-effective treatment modalities. We have previously identified several herbal extracts that demonstrate the potent bio-inhibitory activity of the innate immune response. In particular, Laurus nobilis (LN), or more commonly called bay laurel, demonstrated significant anti-inflammatory function by inhibiting nuclear factor-κB activation. Based upon our original in vitro findings, we have now examined the effects of this herbal extract on a murine dextran sodium sulfate (DSS) model of IBD. Hematoxylin and eosin-stained paraffin sections prepared from DSS-treated animals show clear epithelial damage, including ulcerations, extensive neutrophil infiltration into the mucosal layer, and granuloma formation. Tissue from DSS-treated animals that also received LN extract showed improved tissue morphology more closely resembling that from control animals. In addition, DSS-treated mice with co-administration of LN extract showed a significant reduction in CD4+ antibody staining within the mucosal layer in colonic sections indicating reduced lymphocyte infiltration. Based on these findings, we believe that the administration of LN extracts may be effective in reducing the intestinal epithelial damage seen in human IBD and warrants further investigation through clinical trials. Lay Summary: Inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), manifest as chronic inflammation and ulceration of tissues lining the digestive tract. CD involves inflammation of the deeper layers of the digestive tract, including both the small and large intestines, and less commonly, the upper digestive tract. UC involves inflammation along the lining of the colon and rectum. Steroid or biological treatments for IBD are common, however, they are limited due to significant side effects and/or prohibitive costs. In the present study, we provide evidence for use of the natural product, Laurus nobilis (bay leaf), as a safe and effective anti-inflammatory therapy for IBD.

Incidental finding aortitis: how to handle it?

Aortitis may be an incidental finding at imaging. It refers to inflammation of the aortic wall and sometimes may be hard to differentiate with the periaortitis, inflammation of tissues around the vessel. Their clinical presentation is as varied as their etiologies. Appropriate early management is essential for improving patient prognosis, as the diagnostic approach remains challenging.

Delayed contrast-enhanced magnetic resonance imaging enables detection of pulmonary artery lesions in Takayasu’s arteritis

Delayed contrast-enhanced magnetic resonance imaging (DE-MRI) is a useful technique to identify arterial wall inflammation. The aim of this study was to explore the value of DE-MRI in the evaluation of pulmonary artery (PA) lesions in Takayasu's arteritis (TAK) compared with 18F-fuorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Patients with TAK were recruited for this prospective, observational study. Imaging and clinical assessments were performed concurrently. Only thoracic arteries were evaluated, and they were divided into 18 segments per person. All arterial lesions were evaluated using both PET/CT and DE-MRI. Correlations between both methods were assessed in the PA and thoracic aorta. A receiver operating characteristic (ROC) curve was used to analyze the value of imaging features in detecting disease activity based on National Institutes of Health (NIH) criteria. A total of 24 patients contributed 432 arterial segments. Using PET/CT, correlations between arterial wall DE, thickening, and edema in the PA were 84.52%, 67.92%, and 58.33%, respectively, with Cohen's kappa =0.69, 0.30, and 0.13, respectively; for the thoracic aorta, the values were 86.38%, 80.00%, and 75.92%, respectively, with Cohen's kappa =0.71, 0.52, and 0.372, respectively. There was a significant difference in the incidence of wall DE between the PA and thoracic aorta in patients with clinically active TAK (χ2=6.85, P=0.009). DE-MRI presented a higher area under the curve [area under the curve (AUC); 0.729, P=0.047] than wall thickening and edema in the detection of TAK activity. The wall DE combined with erythrocyte sedimentation rate (ESR) showed improved efficiency (AUC: 0.858, P=0.003). DE-MRI displays appreciable correlations with PET/CT findings and allows for the detection of PA inflammation in patients with TAK; it shows higher values in the thoracic aorta than in the PA. The combination of wall DE and ESR can improve the efficiency of assessing disease status.

Bladder Wall Structure Alterations in Patients Treated With Botulinum Toxin for Detrusor Overactivity - A Morphological Study.

The overactive bladder syndrome (OAB) is a bothersome condition that affects up to 33% of the population. In up to 69% of the cases, the underlying condition is an overactive detrusor (DO). Treatment options rely on behavioral changes, medical treatment, neuromodulation, and invasive treatment, such as injecting botulinum toxin (BoNT) in the detrusor or augmentation cystoplasty. The aim of this study was to evaluate, by morphological assessment on cold-cup biopsies of the bladder, the effect of botulinum toxin injections on the bladder wall, focusing on the histological structure and signs of inflammation and fibrosis. We evaluated consecutive patients with DO that received BoNT intradetrusor injections. We analyzed inflammation and fibrosis in 36 patients, divided into two groups based on their history of BoNT treatment. Our patients underwent at least one round of injections and specimens were compared individually, before and after each injection. A decrease in inflammation was found in 26.3% of the cases, a reactive increase in 31.5%, and no change in 42.1%. No de novo or increase in preexisting fibrosis was found. In some cases, fibrosis diminished after a second round of BoNT. In most cases, BoNT intradetrusor injections in DO patients showed no effect on bladder wall inflammation and actually improved the inflammatory condition of the muscle in a significant number of samples.

The effect of Moringa oleifera leaf extracts against urethane-induced lung cancer in rat model.

Lung cancer is one of the most common malignancies in the world, and chemotherapy can have unfavorable side effects. The aim of the present study is to evaluate the therapeutic anticancer role of Moringa oleifera leaf extracts (MLE) in urethane-induced lung cancer in adult male albino rats as compared to standard chemotherapy. Rats were categorized into four groups (10 rats/group), including negative control rats, urethane lung cancer model rats, MLE-treated lung cancer rats, and cisplatin-treated rats. Estimation of lung index, some biochemical markers of oxidative stress, quantitative real-time polymerase chain reaction (qRT-PCR), and histopathology and transmission electron microscopy were performed. The lung index was significantly increased about one-fold in urethane lung cancer model rats, but it decreased after MLE treatment. Also, MLE was able to improve the induced changes in glutathione, superoxide dismutase, and malondialdehyde concentration to be 3.8 ± 0.4mg/g, 900.6 ± 58 U/g, and 172 ± 24nmol/g, respectively. Additionally, after MLE treatment, the expression of EGFR-mRNA increased by about 50%. Our light and electron microscopic examination revealed that urethane group showed abnormally distributed excessive collagen fibers and the development of papillary adenocarcinoma from hyperplastic Clara cells in the lumen of terminal bronchiole with bronchiolar wall thickening, alveolar collapse, and inflammation. MLE group has moderate amount of collagen fiber and absence of tumor mass and provided more or less restoration of normal lung histology. Moreover, MLE was able to ameliorate the induced changes in mucin and PCNA positive cells in the lung by 10.8 ± 2.3%. Collectively, the current study showed that MLE could be used as anticancer agents alleviating changes associated with lung cancer in a urethane-induced lung cancer bearing rats thereby representing alternative options to toxic chemotherapy.

Pomegranate Peel Extract Reduces Diabetes-induced Collagen Turnover and Biochemical Imbalance in Rat Lung

Diabetes causes lung function disorders. However, pulmonary collagen turnover under diabetes has not been well studied. The purpose of this study was to investigate collagen turnover in lung and to evaluate protective effect of pomegranate peel extract (PPE). Diabetes model in rat was induced by alloxan (250 mg/kg, i.p.). PPE treated rats received 100 mg/kg of PPE for 30 days. PPE was characterized by Gas chromatography–mass spectrometry (GC-MS). Hydroxyproline was determined by colourimetric assay kit, total collagen using ELISA kit and by histopathological assay. Collagenases (MMP-1,-8,-13) wereanalyzed by fluorometric method. Antioxidant enzyme activities and inflammatory marker C-reactive protein (CRP) were evaluated. Diabetes decreases SOD activity and increases CRP level by 33% (p < 0.05) and 125% (p < 0.01), respectively, when compared to the control group. PPE abrogated diabetesinduced SOD activity and CRP level disturbance. Collagenase activity was lower in diabetes and PPE group by 38% (p < 0.05) and 34% (p < 0.05), respectively, when compared to control. Diabetes increased significantly collagen and hydroxyproline by 32% (p < 0.05) and 192% (p < 0.01), respectively, and restored at similar level than controls in PPE group. Lung histopathological assay showed distended alveoli and peribronchial inflammatory cell infiltration in diabetic group. Compared to diabetic, PPE limits inflammatory cell infiltration in lung tissue. Diabetes causes ECM imbalance and enhances inflammation in lung wall, which can be abrogated by PPE.

Imaging Cerebral Arteries Tortuosity and Velocities by Transcranial Doppler Ultrasound Is a Reliable Assessment of Brain Aneurysm in Mouse Models.

During the past few decades, several pathophysiological processes contributing to intracranial aneurysm (IA) rupture have been identified, including irregular IA shape, altered hemodynamic stress within the IA, and vessel wall inflammation. The use of preclinical models of IA and imaging tools is paramount to better understand the underlying disease mechanisms. We used 2 established mouse models of IA, and we analyzed the progression of the IA by magnetic resonance imaging, transcranial Doppler, and histology. In both models of IA, we observed, by transcranial Doppler, a significant decrease of the blood velocities and wall shear stress of the internal carotid arteries. We also observed the formation of tortuous arteries in both models that were correlated with the presence of an aneurysm as confirmed by magnetic resonance imaging and histology. A high grade of tortuosity is associated with a significant decrease of the mean blood flow velocities and a greater artery dilation. Transcranial Doppler is a robust and convenient imaging method to evaluate the progression of IA. Detection of decreased blood flow velocities and increased tortuosity can be used as reliable indicators of IA.

990 IMMUNE-MEDIATED NECROTIZING MYOPATHY IN A PATIENT WITH MULTI-VESSEL CORONARY ARTERY DISEASE

Abstract Inflammatory muscle diseases (often referred to as “inflammatory myopathies” or “myositis”) are a group of muscle diseases characterized by chronic muscle inflammation, inflammation of tissues associated with the muscles, muscle weakness and occasionally muscle pain (depending on the specific case). Ischemic heart disease is the leading cause of cardiovascular mortality in Western countries; the underlying cause is coronary atherosclerosis, a multifactorial disease determined by the concomitant presence of classic cardiovascular risk factors and inflammation of the vessel wall. We present the case of a 60 y/o man who previously underwent CABG (LIMA for ADA e GSV for OM1) for multi-vessel CAD and then developed immune-mediated necrotizing myopathy (probably due to statin treatment) with muscle weakness and pain and with elevation of myolysis markers: in this context, he also presented a recurrence of chest pain with troponin elevation, so that it was needed the integration of functional imaging from myocardial scintigraphy and from cardiac magnetic resonance to understand that troponin elevation (and the chest pain) were due to ischemia and not to muscle damage. This case report underlines how a critical approach to imaging and a deep knowledge of pathophysiology is mandatory in cardiovascular medicine.

297 DEVELOPMENT OF CORONARY ARTERY DISEASE IN A YOUNG ADULT AFFECTED BY TAKAYASU'S ARTERITIS

Abstract Large vessel vasculitis, such as Takayasu's Arteritis (TA), are rare inflammatory diseases affecting multiple vascular districts including the coronary arteries, producing either stenosis and/or aneurysms: these lesions can be found in the same patient and also in the same vessel, with potentially devastating effects. Moreover, TA often affects young people, in the midst of their work and social activity. Ischemic heart disease is the leading cause of cardiovascular mortality in Western countries and is mainly due to coronary atherosclerosis, whose etiopathogenesis is multifactorial and is closely related to the concomitant presence of classic cardiovascular risk factors and inflammation of the vessel wall. We present the case of a young adult, sportsman, with multivessel coronary artery disease developed in the context of a TA bursted seven years before and currently in clinical remission. This complex case required a careful literature review and a multidisciplinary approach, since the best treatment option for coronary lesions induced by TA has not been established: a “watchful waiting” strategy was eventually adopted, considering the poor outcome of both percutaneous and surgical revascularization in this group of patients.

636 LOOKING AT THE BIGGER PICTURE: FROM ACUTE MYOCARDITIS TO THE DIAGNOSIS OF A MULTISYSTEMIC DISEASE

Abstract A 49-year-old man without cardiovascular risk factors, recently diagnosed of asthma and rino-sinusal polyposis, entered the Emergency Department for chest pain, shortness of breath and non-productive cough. The patient was in stable conditions. Laboratory exams showed eosinophilic leucocytosis (WBC 33.000/sqmm, 60% eosinophils) and a mild elevation of C-reactive protein (CRP 2,2 mg/dL). ECG showed a sinus rhythm with flat T-waves in the antero-lateral leads. Troponin values were high but not suggestive of acute myocardial damage (9900 - 9700 ng/L). Echocardiography showed normal biventricular volumes with moderately depressed left ventricular ejection fraction (40%), hypokinesia of the antero-lateral wall in the mid-apical segments and mild pericardial effusion. During the hospital stay he developed progressive respiratory failure, and he was transferred to a tertiary center to perform an endomyocardial biopsy (EMB) in the suspicion of acute myocarditis. EMB showed multifocal interstitial and sub-endocardial inflammatory infiltrates (predominantly eosinophils) with foci of myocellular damage, small vessels wall inflammation with hypertrophy of the muscular tunica. The overall picture was consistent with diffuse moderate eosinophilic myocarditis with small vessels vasculitis. The right heart cath performed in the same procedure and during diuretic therapy showed a normal hemodynamic profile (RAP 5 mmHg, PCWP 13 mmHg, CI 3,7 L/min/sqm). The patient was treated with high dose steroids, first intravenously (methylprednisolone 125 mg/day for three days), then orally (prednisone 80 mg/day) in slow decalage until a maintenance dose of 12.5 mg daily. The recent-onset of asthma with hyper-eosinophilia and rhino-sinus-bronchial syndrome in the light of the present cardiac condition was consistent with eosinophilic granulomatosis with polyangiitis (EGPA). Chest CT showed two areas of ground glass at the left superior and right superior lobes. Other potential haematological and infective causes of hyper eosinophilia and viral causes of myocarditis were ruled out. After the treatment, his clinical conditions improved, ECG was completely normalized, left ventricular systolic function improved (LVEF 50%) and eosinophil count was significantly reduced (Eosinophils 830/sqmm, 8,9%), whereas CT showed resolution of the lung infiltrates. One month after discharge, the patient was still asymptomatic. Cardiac MRI showed normal biventricular ejection fraction (LVEF 55%) with circumferential subendocardial fibrosis involving only the left ventricle. EMB showed a complete resolution of the inflammatory infiltrates and of the vasculitic aspects. Eosinophil count was elevated (5660/sqmm, 36%). Therefore, steroidal dose was raised to 50 mg/day. After rheumatologic evaluation, a steroidal sparing strategy with cyclophosphamide and anti-IL5 antibody Mepolizumab was adopted, with good laboratory response. Three months later, cardiac MRI showed no signs of active disease. No further EMB was scheduled. Through the presentation of this unusual cause of acute myocarditis, we want to underscore the importance of an early referral to a tertiary level center of patients with suspected myocarditis and reduced systolic function and the usefulness of histology to guide medical therapy in specific forms of myocarditis that can lead to a potential complete recovery.

Features of treatment of C. difficile associated diarrhea in patients with new coronavirus infection

The pandemic of a new coronavirus infection in recent years has led to more frequent and aggressive prescription of antibiotic therapy, which could not but affect the intestinal microbiota. In addition, the direct effect of coronavirus on enterocytes leads to the development of subclinical inflammation in the intestinal wall, contributing to the disruption of the qualitative and quantitative composition of the normal intestinal microflora. Against this background, the number of patients with antibiotic-associated diarrhea, including diarrhea caused by C. difficile, including severe ones. Moreover, the number of clostridial diarrhea resistant to classical vancomycin therapy has increased, which dictates the need to find new ways to treat patients and methods for further prevention of such conditions.