Dissecting the cellular mechanism of prostacyclin analogue iloprost in reversing vascular dysfunction in scleroderma

AbstractObjectivesIntravenous iloprost improves Raynaud ‘s phenomenon (RP) and promotes healing of digital ulcers (DU) in scleroderma (SSc). Despite a short half‐life, its clinical efficacy lasts weeks. Endothelial adherens junctions, which are formed by VE‐cadherin clustering between endothelial cells (ECs), regulate endothelial properties includi ng barrier function, endothelial to mesenchymal transition (Endo‐MT), and angiogenesis. We hypothesized that junctional disruption contributes to vascular dysfunction in SSc, and that the protective effect of iloprost is mediated by strengthening of those junctions.MethodsDermal ECs from SSc patients and healthy controls were isolated. The effect of iloprost on ECs was examined using immunofluorescence, permeability assays, Matrigel tube formation, and quantitative PCR.ResultsAdherens junctions in SSc were disrupted compared to normal ECs, as indicated by reduced levels of VE ‐cadherin and increased permeability in SSc ECs (p
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: FULL LENGTH Source Type: research

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Purpose of review Here we review recent literature on the emerging role of nicotinamide adenine dinucleotide (NAD+) metabolism and its dysfunction via the enzyme CD38 in the pathogenesis of rheumatologic diseases. We evaluate the potential of targeting CD38 to ameliorate NAD+-related metabolic imbalance and tissue dysfunction in the treatment of systemic sclerosis (SSc), systemic lupus erythematous (SLE), and rheumatoid arthritis (RA). Recent findings In this review, we will discuss emerging basic, preclinical, and human data that point to the novel role of CD38 in dysregulated NAD+-homeostasis in SSc, SLE, and RA. In...
Source: Current Opinion in Rheumatology - Category: Rheumatology Tags: RAYNAUD PHENOMENON, SCLERODERMA, OVERLAP SYNDROMES AND OTHER FIBROSING SYNDROMES: Edited by John Varga Source Type: research
You are consulted to evaluate a 56 ‐year‐old woman with known Raynaud's phenomenon, finger swelling of several; months’ duration, and new hypertension with a blood pressure of 160/100 mm/Hg. She also reports progressive shortness of breath. Physical examination reveals telangiectasias, sclerodactyly, and proximal skin sclerosis (thick shiny skin on the chest and upper arms), and bibasilar crackles are found on chest examination. Laboratory tests reveal evidence of microangiopathic hemolytic anemia, thrombocytopenia, and elevation of the serum creatinine level (previously normal), and chest computed tomography sho...
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Expert Perspectives On Clinical Challenges Source Type: research
Publication date: Available online 1 October 2019Source: Best Practice &Research Clinical RheumatologyAuthor(s): Francisca Alves, Margarida GonçaloAbstractSkin lesions occur, often at very early stages, in many of the most frequent inflammatory rheumatic diseases such as in systemic lupus erythematosus (SLE), dermatomyositis (DM), systemic sclerosis (SSc), Sjögren's syndrome, rheumatoid arthritis (RA), and psoriatic arthritis.It is important to recognize the different specific cutaneous lesions in SLE (e.g., “butterfly” rash in acute, annular or psoriasiform photosensitive lesions in the subacut...
Source: Best Practice and Research Clinical Rheumatology - Category: Rheumatology Source Type: research
Abstract Systemic sclerosis is a complex autoimmune connective tissue disease which carries a significant burden of disease-related morbidity including potentially life-threatening complications. Systemic sclerosis can affect all the major organs and therefore, although the disease is uncommon, many hospital-based specialists are involved in patient care. Vascular disease (e.g. Raynaud's phenomenon) is an almost universal symptom in patients with systemic sclerosis and is often the earliest manifestation of the disease. Systemic sclerosis not uncommonly can overlap with other rheumatological conditions (e.g. rheum...
Source: British Journal of Hospital Medicine - Category: Internal Medicine Authors: Tags: Br J Hosp Med (Lond) Source Type: research
Osman K. Yilmaz1, Stefanie Haeberle1, Meifeng Zhang1, Marvin J. Fritzler2, Alexander H. Enk1 and Eva N. Hadaschik1,3* 1Department of Dermatology, University of Heidelberg, Heidelberg, Germany 2Mitogen Advanced Diagnostics Laboratory, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada 3Department of Dermatology, University Hospital of Essen, Essen, Germany Due to a missense mutation in the Foxp3 gene, scurfy mice are deficient in functional regulatory T cells (Treg). The consequent loss of peripheral tolerance manifests itself by fatal autoimmune mediated multi-organ disease. Previous studies...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
This article presents an overview on recent advances in optical non-invasive diagnostics of the peripheral hemodynamics of the upper and lower limbs in rheumatological and endocrinological profile patients. Among these are laser Doppler flowmetry (LDF), tissue reflectance oximetry (TRO), pulse oximetry (PO) and fluorescent spectroscopy (FS). The laser Doppler flowmetry method allows for investigating the blood flow in the microcirculatory bed in vivo. The method is based on probing the tissue with laser radiation and analyzing back reflected from the tissue radiation partially scattered from moving red blood cells (Bonner...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusion Trochlear pain (trochleodynia) is becoming recognized as a set of disorders that can present in isolation or concomitantly with co-existing migraines, tension-type headaches, or other headache disorders, possibly explaining subpar symptom control in a small but significant number of individuals globally. Trochleodynia features unilateral periocular pain that may involve the ipsilateral hemicranium. Pain exacerbation occurs with trochlear palpation and supraduction of the affected eye especially in the adducted position. Trochleodynia may respond to oral NSAIDs if symptoms are mild and of recent onset. While ora...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
ConclusionOverlap myositis stands out as a distinct entity as compared to PM and DM, featuring more extramuscular involvement and more severe infections. Close monitoring is recommended in this subset for early detection and treatment of possible complications.
Source: International Journal of Rheumatic Diseases - Category: Rheumatology Authors: Tags: ORIGINAL ARTICLE Source Type: research
Authors: van Roon AM, Huisman CC, van Roon AM, Zhang D, Stel AJ, Smit AJ, Bootsma H, Mulder DJ Abstract OBJECTIVE: To assess the presence of a systemic sclerosis (SSc) pattern on nailfold capillary microscopy (NCM) in patients with Raynaud phenomenon (RP) and to explore its association with abnormal pulmonary function tests (PFT). METHODS: NCM patterns were assessed in 759 consecutive patients with RP. Patterns were classified as normal (n = 354), nonspecific (n = 159), or SSc pattern (n = 246). Abnormal PFT was defined as forced vital or diffusion capacity
Source: Journal of Rheumatology - Category: Rheumatology Tags: J Rheumatol Source Type: research
ConclusionOur study confirmed that many ACA ‐positive cases can be classified into an autoimmune disease type on presentation.
Source: International Journal of Rheumatic Diseases - Category: Rheumatology Authors: Tags: ORIGINAL ARTICLE Source Type: research
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