Inflammation Of Vessels Research Articles

Number of inflamed coronary vessels in prediction of cardiac death and MACE among patients undergoing routine CCTA: the Oxford Risk Factors And Non-Invasive Imaging (ORFAN) Study

Abstract Background Coronary inflammation can be assessed by the changes in perivascular adipose tissue on routine coronary CT angiograms (CCTA). Fat attenuation index score (FAI Score) quantifies the degree of inflammation in each epicardial coronary artery, and adjusts for age, sex, scan technical parameters, biological and anatomical factors. Coronary inflammation assessment in a single coronary artery was previously shown to be predictive of cardiac events in the CRISP-CT study. However, the impact of inflammation in multiple coronary arteries on clinical outcome remains unclear. Purpose To evaluate the prognostic value of the number of inflamed coronary arteries with high inflammation in the risk of cardiac death, and major adverse cardiac events (MACE). Methods In a nested cohort within the Oxford Risk Factors And Non-invasive imaging (ORFAN) study, consecutive patients (n=3,393) who underwent routine clinical CCTA were followed up over a median(IQR) 7.7(6.4-9.1) years for cardiac mortality, and MACE (including myocardial infarction, new onset heart failure, cardiac mortality). FAI Score was calculated for each of the 3 epicardial coronary arteries. Results The number of inflamed arteries (FAI Score >75th centile) showed an additive impact on cardiac mortality compared with no inflamed arteries (all vessels FAI Score <25th centile), with hazard ratio 29.8 (95% CI 13.9-63.9, p<0.001) for 3 inflamed arteries, HR 20.4 (95% CI 9.4-44.7, p<0.001) for 2 inflamed arteries, and HR 13.0 (95% CI 5.9-28.8, p<0.001) for 1 inflamed artery. (Panel A) Similarly, patients with multiple inflamed arteries showed progressively higher risk for MACE (HR 7.2, 8.3 and 12.6 for 1-, 2- and 3-inflamed arteries respectively compared to patients with no inflamed artery). (Panel B) Patients with no inflamed arteries showed very low event rates for cardiac mortality and MACE. In patients with no obstructive CAD (n=2,651), similar trends were observed whereby patients with 3-inflamed arteries showed highest risk for cardiac mortality (Panel C) and MACE (Panel D), with intermediate risk for those with 1 or 2 inflamed arteries. Conclusion The number of coronary arteries with high inflammation, measured by FAI Score from routine CCTA, is associated with adverse cardiovascular events and cardiac mortality in an additive dose-response manner.

Difficult-to-treat Takayasu arteritis: a case-based review.

Takayasu arteritis is a rare chronic inflammatory large vessel vasculitis which affects the aorta and its large branches. The diagnosis is based on the 2022 ACR/EULAR classification criteria for Takayasu arteritis. The management of this vasculitis is challenging. Although it is corticosteroid-responsive, relapses and disease progression are common. Thus, it is possible to resort to alternative conventional synthetic disease-modifying anti-rheumatic drugs and biologics, as second-line such as tumor necrosis factor-alpha inhibitors, tocilizumab, or JAK inhibitors as second-line agents is possible. Nevertheless, in some complex cases, the vasculitis remains active despite different proposed therapeutic lines, and a multitarget approach could induce sustained remission. We report herewith a case of 33-female patient with a refractory Takayasu arteritis which remained active after three different therapeutic lines with tocilizumab, then infliximab, then Upadacitinib. Finally, we consider a successful multitarget approach with a combination of infliximab, Upadacitinib, and methotrexate.

EPIZOOTIC LYMPHANGITIS - THE FORGOTTEN DISEASE OF UNGULATES

Epizootic lymphangitis, as a forgotten disease of ungulates, again attracts the attention of veterinarians and zoologists. This infection, caused by pathogenic microorganisms, leads to inflammation of the lymphatic vessels, which can cause serious complications and even death of the animal. Despite the rarity of cases in recent decades, epizootic lymphangitis leaves a significant mark on the history of veterinary medicine, causing alertness among specialists. The purpose of the review. To summarize current scientific data on the etiology, pathogenesis, diagnosis and prevention of equine epizootic lymphangitis in order to assess the risk of introduction and spread of the disease to disease-free territories. Results. The review presents the epidemiological characteristics of the etiological agent of the disease, possible main and intermediate reservoirs of the pathogen in nature, mechanisms of transmission of infection, promising directions for the development of prevention and treatment tools. Conclusion. The causes of epidemics remain a mystery, but the factors contributing to the spread of the disease range from lack of vaccinations to unfavorable conditions of detention. The fight against this disease should be carried out through vaccination, isolation and quarantine of sick animals, disinfection of animal housing and equipment, as well as surveillance.

Vasculitis associated with VEXAS syndrome.

To define the prevalence, distribution, and characteristics of patients with VEXAS who have confirmed vasculitis. Patients with VEXAS syndrome, verified by positive UBA1 mutation, were included. Chart review was performed to identify. characteristics and outcomes. Vasculitis diagnosis was based on either histopathology showing vascular inflammation or non-invasive angiography findings. Summary statistics were calculated. Eighty-nine patients met inclusion criteria. All were male with a median age of onset of 66.9 years (IQR 60.1, 72.7). Median (IQR) follow up was 3.8(2.2-5.5) years during which 21 patients (23.6%) had evidence of vasculitis. Vasculitis subtypes included small vessel vasculitis (19.1%), cutaneous medium vessel vasculitis (2.2%), and large vessel vasculitis (2.2%). No patient had more than one vessel size involved. Histopathology in small vessel vasculitis patients was consistent with cutaneous leukocytoclastic vasculitis in the majority, though one patient had leukocytoclastic peritubular capillaritis on renal biopsy. Cranial symptoms (headache, vision changes, or jaw pain) were noted in 18.0%. Two additional patients not experiencing cranial symptoms exhibited large vessel involvement with confirmed carotid thickening on non-invasive angiography; one of these had a positive temporal artery biopsy. VEXAS syndrome manifests as a variable vessel vasculitis in a quarter of patients, with cutaneous small and medium vessel involvement being particularly common. Some patients may have positive ANCA serologies or even renal vasculitis leading to misdiagnosis. Cranial symptoms are common and may mimic giant cell arteritis, though documented large vessel inflammation is rare.

Pulmonary-Renal Syndrome in the Elderly: Immunosuppressive Treatment – Case Report

Pulmonary-renal syndrome is called alveolar hemorrhage accompanied by glomerulonephritis. The above condition can occur as a manifestation of ANCA-associated granulomatosis with vasculitis. The course of the disease varies from mild, limited inflammation to rapid progression with multi-organ changes that can be life-threatening. The mainstay of therapy is immunosuppression - both in the acute phase of the disease and after clinical improvement. Unfortunately, common causes of death in addition to complications of the disease include side effects of immunosuppressive treatment. A 72-year-old man is transferred to the Nephrology Unit for acute kidney injury of unclear etiology. On the basis of clinical examination, laboratory and imaging studies, a diagnosis of systemic small vessel inflammation with c-ANCA occupying the kidneys, lungs and intestines was made. Due to acute respiratory failure, the patient was transferred to the ICU, where renal replacement therapy, plasmapheresis, steroid pulses and cyclophosphamide were administered. After clinical improvement, it was decided to continue cyclophosphamide therapy and monitor blood IgG levels. Unfortunately, 4 months later, the patient died of multiple organ failure caused by septic shock of bacterial etiology. In the described case, age and comorbidities were the biggest risk factors for infectious complications of immunosuppression. The population is aging, so it is necessary to analyze the current standards of immunosuppressive treatment to improve the prognosis of the elderly.

TNF-α inhibitors in the management of refractory granulomatosis with polyangiitis: A report of two cases

Granulomatosis with polyangiitis (GPA) is a type of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) that causes granulomatous necrotizing inflammation of small blood vessels. The goal of AAV treatment is to create a long-term remission. For inducing remission, the European League Against Rheumatism recommends using glucocorticoids (GCs) in combination with either cyclophosphamide (CYC) or rituximab (RTX). Despite this, in 10-40% the disease is resistant to initial treatment. In this report, we present two cases of refractory GPA that successfully achieved long-term remission using tumor necrosis factor-α inhibitors. The first case is a 27-year-old woman with GPA with involvement of upper airway, breast and central nervous system with active disease despite treatment with high dose GCs, CYC and RTX, successfully treated with infliximab and the disease was in complete remission for 54 months. The second case is a 35-year-old man with GPA with arthritis, lung cavitary lesions and nephritis resistant to treatment with high dose GCs, CYC and RTX, treated with adalimumab and the disease was in complete remission for 40 months.

Differential diagnosis between rheumatoid nodules and fibrocaseous tubercles in the lung: A case series

The histological similarities between rheumatoid nodules and post-primary fibrocaseous tubercles in the lung may present a significant challenge in differential diagnosis. Differential diagnosis of fibrocaseous tubercles and rheumatoid nodules is crucial in clinical practice, particularly due to the high risk of co-existing fibrocaseous tuberculosis in rheumatoid arthritis. This condition increases the likelihood of military dissemination and mortality, especially in elderly patients, with elderly women being at the greatest risk. This case series aims to differentiate these two pathological entities based on the clinical histories and histological analyses of surgical specimens from two patients. The main histological marker for RhNod is the presence of vascular remnants within the fibrinoid necrotic area, reflecting the vascular origin of RhNods. Additional supporting evidence for the rheumatoid nature of the process includes the presence of inflamed blood vessels elsewhere in the lung (such as non-specific, fibrinoid necrotic, and/or granulomatous autoimmune vasculitis), as well as the potential presence of co-existent interstitial pneumonitis, with or without pleuritis. In contrast, the necrotic tuberculous process is characterized by coalescent necrosis that does not respect anatomical borders and lacks structural remnants of lung tissue, which is a hallmark of tuberculosis pathology.

Pericyte phenotype switching alleviates immunosuppression and sensitizes vascularized tumors to immunotherapy in preclinical models.

T cell-based immunotherapies are a promising therapeutic approach for multiple malignancies, but their efficacy is limited by tumor hypoxia arising from dysfunctional blood vessels. Here, we report that cell-intrinsic properties of a single vascular component, namely the pericyte, contribute to the control of tumor oxygenation, macrophage polarization, vessel inflammation, and T cell infiltration. Switching pericyte phenotype from a synthetic to a differentiated state reverses immune suppression and sensitizes tumors to adoptive T cell therapy, leading to regression of melanoma in mice. In melanoma patients, improved survival is correlated with enhanced pericyte maturity. Importantly, pericyte plasticity is regulated by signaling pathways converging on Rho kinase activity, with pericyte maturity being inducible by selective low-dose therapeutics that suppress pericyte MEK, AKT, or notch signaling. We also show that low-dose targeted anticancer therapy can durably change the tumor microenvironment without inducing adaptive resistance, creating a highly translatable pathway for redosing anticancer targeted therapies in combination with immunotherapy to improve outcome.

Transcriptome meta-analysis of Kawasaki disease in humans and mice.

Kawasaki Disease (KD) affects young children less than five years old with severe blood vessel inflammation. Despite being treatable, the causes and mechanisms remain elusive. This study conducted a meta-analysis of RNA sequencing (RNA-seq) data from human and animal models to explore KD's transcriptomic profile and evaluate animal models. We retrieved bulk and single-cell RNA-seq data from Gene Expression Omnibus, with blood and coronary artery samples from KD patients, aorta samples from KD mouse models (Lactobacillus casei cell wall extract-injected mice), and their controls. Upon consistent quality control, we applied Fisher's exact test to assess differential gene expression, followed by an enrichment analysis of overlapping genes. These studies identified 400 differentially expressed genes in blood samples of KD patients compared to controls and 413 genes in coronary artery samples. The data from KD blood and KD coronary artery samples shared only 16 differentially expressed genes. Eighty-one genes overlapped between KD human coronary arteries and KD mouse aortas, and 67 of these 81 genes were regulated in parallel in both humans and mice: 30 genes were up-regulated, and 37 were down-regulated. These included previously identified KD-upregulated genes: CD74, SFRP4, ITGA4, and IKZF1. Gene enrichment analysis revealed significant alterations in the cardiomyopathy pathway. Single-cell RNAseq showed a few significant markers, with known KD markers like S100A9, S100A8, CD74, CD14, IFITM2, and IFITM3, being overexpressed in KD cohorts. Gene profiles obtained from KD human coronary artery are more compatible with data from aorta samples of KD mice than blood samples of KD humans, validating KD animal models for identifying therapeutic targets. Although blood samples can be utilized to discover novel biomarkers, more comprehensive single-cell sequencing is required to detail gene expression in different blood cell populations. This study identifies critical genes from human and mouse tissues to help develop new treatment strategies for KD.

Imaging in vasculitis.

Systemic vasculitides are characterized by inflammation of blood vessels. Their classification is based on the size of the blood vessels involved - large, medium, or small. Vasculitis early diagnosis and reliable monitoring are crucial to establish a treatment plan and prevent serious complications. Based on these considerations and depending on the location of the affected vessels, the importance of imaging modalities including ultrasonography (US), magnetic resonance Imaging (MRI), magnetic resonance angiography (MRA), computed tomography (CT), computed tomography angiography (CTA), and [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) has progressively increased. In addition to physical exam and laboratory data, these imaging tools offer complementary information about vascular changes occurring in vasculitis.This review summarizes the different imaging modalities being utilized to diagnose and monitor vasculitis. The most recent update for the use of imaging in vasculitis is referenced in the 2023 European Alliance of Associations for Rheumatology (EULAR) recommendations and the American College of Rheumatology (ACR) guidelines in 2021. Recent advances in PET imaging in large vessel vasculitis include improved technological imaging acquisition and the use of novel radiotracers for cellular and immune targets. FDG-PET has now been demonstrated to have high sensitivity and specificity to detect temporal arteritis. Imaging plays a significant role in the evaluation of vasculitis and continues to gain importance in the diagnosis and monitoring of disease activity. Differences exist between the ACR guidelines, which advocates for temporal artery biopsy, and the EULAR guidelines, which favors imaging modalities for the initial evaluation and diagnosis of large vessel vasculitis (LVV). Prerequisites for appropriate clinical management utilizing imaging in patients with vasculitis are the availability and access to skilled clinicians to interpret the images and the cost of these techniques not being prohibitive.

MTOR signalling controls the formation of smooth muscle cell-derived luminal myofibroblasts during vasculitis

The accumulation of myofibroblasts within the intimal layer of inflamed blood vessels is a potentially catastrophic complication of vasculitis, which can lead to arterial stenosis and ischaemia. In this study, we have investigated how these luminal myofibroblasts develop during Kawasaki disease (KD), a paediatric vasculitis typically involving the coronary arteries. By performing lineage tracing studies in a murine model of KD, we reveal that luminal myofibroblasts develop independently of adventitial fibroblasts and endothelial cells, and instead derive from smooth muscle cells (SMCs). Notably, the emergence of SMC-derived luminal myofibroblasts—in both mice and patients with KD, Takayasu’s arteritis and Giant Cell arteritis—coincided with activation of the mechanistic target of rapamycin (mTOR) signalling pathway. Moreover, SMC-specific deletion of mTOR signalling, or pharmacological inhibition, abrogated the emergence of luminal myofibroblasts. Thus, mTOR is an intrinsic and essential regulator of luminal myofibroblast formation that is activated in vasculitis patients and therapeutically tractable. These findings provide molecular insight into the pathogenesis of coronary artery stenosis and identify mTOR as a therapeutic target in vasculitis.

Vasculitis associated with psoriatic arthritis: a case report

BackgroundPsoriatic arthritis is a chronic inflammatory condition associated with psoriasis, which affects joints. The coexistence of vasculitis, an inflammation of blood vessels, with psoriatic arthritis is rare, highlighting a complex interplay between autoimmune diseases that affect both joints and vascular structures.Case presentationWe report on a 56-year-old male with a long-standing history of psoriasis and psoriatic arthritis, who presented with new-onset skin lesions and neurological symptoms. Clinical evaluations confirmed the presence of leukocytoclastic vasculitis and asymmetric sensory motor axonal neuropathy. The absence of positive results from various standard tests led to a challenging diagnostic process, ultimately pointing towards vasculitis associated with psoriatic arthritis. The patient was treated with corticosteroids and immunosuppressive therapy, leading to partial symptom improvement.ConclusionsThis case underlines the complex and often overlapping nature of autoimmune conditions, particularly the occurrence of vasculitis in patients with psoriatic arthritis, which is rare. It stresses the importance of considering vasculitis in patients with psoriatic arthritis who present with unexplained skin lesions and neurological symptoms. This case adds to the spectrum of psoriatic disease manifestations and suggests a need for further research to explore the underlying mechanisms and improve management strategies.

Giant Cell Arteritis and Takayasu Arteritis: Are They Similar or Different?

Vasculitis is a group of heterogeneous conditions characterised by inflammation of blood vessels. Based on the predominant size of the affected vessel, vasculitis is classified into small, medium, and large vessel vasculitis (LVV). Giant cell arteritis (GCA) and Takayasu’s arteritis (TAK) are the two major types of LVV. GCA was thought to affect only the external carotid artery and its branches, whereas, TAK was thought to affect the aorta and its major branches. Advances in imaging techniques have led to a better understanding of these conditions. It has become increasingly clear that GCA can involve the aorta and its branches. GCA and TAK have overlapping features like propensity to affect the aorta and its branches, similar histopathology, and similar clinical features. However, there are differences in age, geographic location, genetics, and predominant vascular territory involvement. There are subtle differences in clinical features. Are these conditions different ends of the same spectrum or different conditions with similar features? This review compares and contrasts these two conditions based on epidemiology, genetics, pathology, predominant vascular territory involvement, and any differential response to treatment. Based on current evidence, GCA and TAK seem to be distinct conditions and not different ends of the same spectrum.

Update on Takayasu arteritis: Year in review 2024.

Takayasu arteritis is an uncommon systemic inflammatory large vessel vasculitis affecting women in their third and fourth decades frequently. The disease poses considerable morbidity and mortality owing to the involvement of the aorta and its major branches. Treatment comprises medical and vascular interventions, tailored to each patient. We review the high-impact publications of the year 2023 up to April 2024, which provide great insight into clinical, biomarker, imaging, pathogenetic, and therapeutic updates.

Violaceous nodules of the extensor joints - a clinicopathological challenge.

Antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a condition characterized by vessel inflammation and may have a variety of etiologies. Among these, cocaine and its common adulterant, levamisole, have been described to contribute to the development of AAV with distinct cutaneous manifestations. Classically, these manifestations involve purpuric or necrotic lesions involving the ears, nose, and extremities. However, we present a case of cocaine-induced AAV presenting with violaceous nodules on the dorsal hands in order to demonstrate that this condition may not always present with retiform purpura and skin necrosis.

Kawasaki Disease

Kawasaki disease (KD) is a type of acute inflammation of blood vessels, accompanied by a fever, for which the cause is yet unknown. It primarily affects children who are under the age of five. Kawasaki disease (KD) frequently results in the development of coronary artery lesions (CALs), which include dilated arteries, coronary artery aneurysms (CAAs), and potentially life-threatening myocardial infarction. under the age of five. Kawasaki disease (KD) frequently results in the development of coronary artery lesions (CALs). This case report aims to further explore the diagnosis and the management of KD. In this case report we discuss a 3-year-old male patient who was diagnosed with KD with the main complaints of fever, red eyes, rash, redness of lips with cracked and oral cavity. Patient’s lab work showed hypoalbuminemia, increased D-Dimer, and increased Troponin I. Electrocardiography and echocardiography was performed to observe cardiac complication. Soon aspirin and IVIG and showed an improvement. The child was treated for 6 days and then controlled at the outpatient clinic. Keywords: Kawasaki Disease, Pediatric, IVIG, Aspirin

Biomimetic Nanoparticles for the Diagnosis and Therapy of Atherosclerosis.

Atherosclerosis (AS) is a chronic inflammation of blood vessels, which often has no obvious symptoms in the early stage of the disease, but when atherosclerotic plaques are formed, they often cause lumen blockage, and even plaque rupture leads to thrombosis, that is the essential factor of cardiovascular events, for example myocardial infarction, cerebral infarction, and renal atrophy. Therefore, it is considerably significant for the early recognition and precise therapy of plaque. Biomimetic nanoparticles (BNPs), especially those coated with cell membranes, can retain the biological function of cell membranes or cells, which has led to extensive research and application in the diagnosis and treatment of AS in recent years. In this review, we summarized the roles of various key cells in AS progression, the construction of biomimetic nanoparticles based on these key cells as well as their applications in AS diagnosis and therapy. Furthermore, we give a challenge and prospect of biomimetic nanoparticles in AS, hoping to elevate their application quality and the possibility of clinical translation.

Effect of photobiomodulation with different wavelengths on periodontal repair in non-hyperglycemic and hyperglycemicrats.

Hyperglycemic conditions is associated with more severe periodontitis and poorer outcomes after nonsurgical periodontal treatment (NPT). Then, these patients are candidates for adjunctive therapy associated with NPT. This study evaluates the effect of photobiomodulation (PBMT) at different wavelengths on periodontal repair in non-hyperglycemic/hyperglycemic animals. Sixty-four rats were submitted to induction of periodontitis by ligatures. Hyperglycemia was induced in half of these animals, whereas the other half remained non-hyperglycemic. The animals were subdivided into 4 groups according to the PBMT protocol applied at the time of ligature removal (n = 8): CTR: Without PBMT; IRL: PBMT with infrared laser (808 nm); RL: PBMT with red laser (660 nm); and RL-IRL: PBMT with red (660 nm) and infrared laser (808 nm). After a period of 7 days, the animals were euthanized. The parameters assessed by microtomography were the bone volume relative to total tissue volume (BV/TV%), distance from the cemento-enamel junction to the top of the bone crest (CEJ-CB), trabecular thickness, space between trabeculae, and number of trabeculae. Additionally, the percentage of inflammatory cells, blood vessels, and connective tissue matrix were assessed by histomorphometric analysis. PBMT reduced bone loss and increased trabecular density in hyperglycemic animals (p < .05), with RL being more effective in reducing linear bone loss (CEJ-CB), whereas RL-IRL was more effective in maintaining BV/TV%. PBMT reduced blood vessels and increased the connective tissue component in hyperglycemic animals (p < .05). RL-IRL reduced inflammatory cells regardless of the systemic condition of the animal (p < .05). PBMT (RL, RL-IRL) improves the repair of periodontal tissues in hyperglycemic animals.

Biomimetic nanoplatform treats myocardial ischemia/reperfusion injury by synergistically promoting angiogenesis and inhibiting inflammation

After myocardial ischemia/reperfusion injury (MI/RI), endothelial cell injury causes impaired angiogenesis and obstruction of microcirculation, resulting in an inflammatory outburst that exacerbates the damage. Therefore, synergistic blood vessel repair and inflammation inhibition are effective therapeutic strategies. In this study, we developed a platelet membrane (PM)-encapsulated baicalin nanocrystalline (BA NC) nanoplatform with a high drug load, BA NC@PM, which co-target to endothelial cells and macrophages through the transmembrane proteins of the PM to promote angiogenesis and achieve anti-inflammatory effects. In vitro cell scratch assays and transwell assay manifested that BA NC@PM could promote endothelial cell migration, as well as increase mRNA expression of CD31 and VEGF in the heart after treatment of MI/RI mice, suggesting its favorable vascular repair function. In addition, the preparation significantly reduced the expression of pro-inflammatory factors and increased the expression of anti-inflammatory factors in plasma, promoting the polarization of macrophages. Our study highlights a strategy for enhancing the treatment of MI/RI by promoting angiogenesis and regulating macrophage polarization via the biomimetic BA NC@PM nanoplatform.

The Role of Angiopoietins in Cardiovascular Outcomes of Kidney Transplant Recipients: An Ancillary Study from the FAVORIT

Plain Language SummaryWe have identified compelling insights into the role of two proteins called angiopoietin 1 and 2, which are needed, in balance, for healthy blood vessels to form. In the case of kidney transplants from deceased donors, we found that high levels of angiopoietin-2, suggest a higher risk of future heart problems, kidney transplant failure, and even death. As such, our study reaffirms that high levels of angiopoietin-2 in the blood is a marker of blood vessel injury and inflammation. Notably, when we included information about these proteins along with the regular medical details, we were better at predicting important clinical outcomes. Understanding these proteins could help us figure out which KTRs are at a higher risk, so we can take better care of them and potentially improve their outcomes.