In vivo approaches to investigate ANCA-associated vasculitis: lessons and limitations

Anti-neutrophil cytoplasm autoantibody (ANCA)-associated diseases are autoimmune conditions characterized by necrotizing inflammation of small blood vessels. The immunogenesis and etiology of these conditions are unknown, but our knowledge of the immunopathogenesis has increased considerably in recent years. In this review, we discuss the animal models currently used to investigate the mechanisms of vascular injury and to test novel therapies. We outline their advantages and limitations and propose potential directions for future research

Beneficial Effects of Alternate Dietary Regimen on Liver Inflammation, Atherosclerosis and Renal Activation

Background: Alternate day calorie restriction (CR) has been shown to be almost as beneficial as daily CR. The question arises whether this concept is also applicable to alternating dietary composition. Objective: To seek evidence that alternating high cholesterol (HC) - cholesterol-free (CON) Western diet can effectively diminish hepatic and renal inflammation and cardiovascular risk factors as compared with daily HC-supplemented Western diet. Design: Four groups of ApoE*3Leiden mice, a humanized model for atherosclerosis, were subjected to different feeding treatments for 16 weeks. Mice were fed CON diet; CON diet with 1% w/w cholesterol (HC); alternate (ALT) diet regimen of CON (4 days) and HC (3 days); or CON diet supplemented with 0.43% (w/w) cholesterol (MC), with overall dietary cholesterol intake equal to ALT. Plasma was analyzed for cardiovascular risk factors, aorta for atherosclerotic lesion formation, and liver and kidney for inflammation. Results: ALT diet but not MC was almost as effective as daily CON feeding in preventing disease development. Compared to HC, the ALT group showed 62% lower hepatic nuclear factor kappa B (NF-?B) activity (P<0.001), a reduction of the circulating inflammatory markers E-selectin (-20%; P<0.05), vascular cell adhesion molecule 1 (VCAM-1; -15%; P<0.05) and Serum Amyloid A (SAA; -31%; P<0.05), smaller atherosclerotic lesion sizes (-51%; 46497±10791 µm2 vs. 94664±16470 µm2; P<0.05) and diminished renal expression of specific inflammation and activation markers (VCAM-1, -27%; P<0.05; monocyte chemotactic protein-1 (MCP-1); -37%; P<0.01). Conclusion: Alternate HC-CON feeding reproduced most of the beneficial effects of daily cholesterol-free diet, including strongly diminished hepatic, vascular and renal activation and inflammation; also atherosclerosis was reduced by half as compared to HC, albeit still higher compared to the CON group. © 2011 Wielinga et al

Mechanisms and pathophysiology of SARS-CoV-2 infection of the adipose tissue

Obesity is an independent risk factor for severe COVID-19, yet there remains a lack of consensus on the mechanisms underlying this relationship. A hypothesis that has garnered considerable attention suggests that SARS-CoV-2 disrupts adipose tissue function, either through direct infection or by indirect mechanisms. Indeed, recent reports have begun to shed some light on the important role that the adipose tissue plays during the acute phase of infection, as well as mediating long-term sequelae. In this review, we examine the evidence of extrapulmonary dissemination of SARS-CoV-2 to the adipose tissue. We discuss the mechanisms, acute and long-term implications, and possible management strategies to limit or ameliorate severe disease and long-term metabolic disturbances

Myeloperoxidase:Molecular Mechanisms of Action and Their Relevance to Human Health and Disease

Myeloperoxidase (MPO) is a heme-containing peroxidase abundantly expressed in neutrophils and to a lesser extent in monocytes. Enzymatically active MPO, together with hydrogen peroxide and chloride, produces the powerful oxidant hypochlorous acid and is a key contributor to the oxygen-dependent microbicidal activity of phagocytes. In addition, excessive generation of MPO-derived oxidants has been linked to tissue damage in many diseases, especially those characterized by acute or chronic inflammation. It has become increasingly clear that MPO exerts effects that are beyond its oxidative properties. These properties of MPO are, in many cases, independent of its catalytic activity and affect various processes involved in cell signaling and cell-cell interactions and are, as such, capable of modulating inflammatory responses. Given these diverse effects, an increased interest has emerged in the role of MPO and its downstream products in a wide range of inflammatory diseases. In this article, our knowledge pertaining to the biologic role of MPO and its downstream effects and mechanisms of action in health and disease is reviewed and discussed. Antioxid. Redox Signal. 11, 2899-2937