Proteomic profiling of the large-vessel vasculitis spectrum identifies shared signatures of innate immune activation and stromal remodelling.

Background: Takayasu arteritis (TAK) and giant cell arteritis (GCA), the most common forms of large-vessel vasculitis (LVV), can result in serious morbidity. Understanding the molecular basis of LVV should aid in developing better biomarkers and treatments.

Methods: Plasma proteomic profiling of 184 proteins was performed in two cohorts.

EPAS1 Attenuates Atherosclerosis Initiation at Disturbed Flow Sites Through Endothelial Fatty Acid Uptake.

Background: Atherosclerotic plaques form unevenly due to disturbed blood flow, causing localized endothelial cell (EC) dysfunction. Obesity exacerbates this process, but the underlying molecular mechanisms are unclear. The transcription factor EPAS1 (HIF2A) has regulatory roles in endothelium, but its involvement in atherosclerosis remains unexplored.

The actions of methotrexate on endothelial cells are dependent on the shear stress-induced regulation of one carbon metabolism.

Objectives: The disease-modifying anti-rheumatic drug methotrexate (MTX) is recognized to reduce cardiovascular risk in patients with systemic inflammatory diseases. However, the molecular basis for these cardioprotective effects remains incompletely understood. This study evaluated the actions of low-dose MTX on the vascular endothelium.

Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis.

Background: Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures.

Objectives: We aimed to investigate somatostatin receptor 2 (SST) as a novel inflammation-specific molecular imaging target in LVV.

Methods: In a prospective, observational cohort study, in vivo arterial SST expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using Ga-DOTATATE and F-FET-βAG-TOCA.

Hydroxychloroquine as an Immunomodulatory and Antithrombotic Treatment in Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an acquired highly prothrombotic disorder in which thrombo-inflammatory antiphospholipid antibodies (aPL) cause thrombosis via multiple mechanisms, including endothelial damage and activation. Obstetric complications in APS are caused by placental thrombosis, inflammation and complement activation. Anticoagulation is poorly effective in some patients especially those with triple positive aPL who are at ~30% risk of thrombosis recurrence within 10 years.