Autoimmune rheumatic diseases : An update on the role of atherogenic electronegative ldl and potential therapeutic strategies

Altres ajuts: Vascular and Medicinal Research Fund, Texas Heart Institute (#765-64050), Houston, TX, USA; Ministry of Science and Technology (Taiwana grant MOST 107-2314-B-039-053-MY3); Ministerio de Sanidad, Spain (co-financed by Fondo Europeo de Desarrollo Regional (FEDER)).Atherosclerosis has been linked with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Autoimmune rheumatic diseases (AIRDs) are associated with accelerated atherosclerosis and ASCVD. However, the mechanisms underlying the high ASCVD burden in patients with AIRDs cannot be explained only by conventional risk factors despite disease-specific factors and chronic inflammation. Nevertheless, the normal levels of plasma low-density lipoprotein (LDL) cholesterol observed in most patients with AIRDs do not exclude the possibility of increased LDL atherogenicity. By using anion-exchange chromatography, human LDL can be divided into five increasingly electronegative subfractions, L1 to L5, or into electropositive and electronegative counterparts, LDL (+) and LDL (−). Electronegative L5 and LDL (−) have similar chemical composi-tions and can induce adverse inflammatory reactions in vascular cells. Notably, the percentage of L5 or LDL (−) in total LDL is increased in normolipidemic patients with AIRDs. Electronegative L5 and LDL (−) are not recognized by the normal LDL receptor but instead signal through the lectin-like oxidized LDL receptor 1 (LOX-1) to activate inflammasomes involving interleukin 1β (IL-1β). Here, we describe the detailed mechanisms of AIRD-related ASCVD mediated by L5 or LDL (−) and discuss the potential targeting of LOX-1 or IL-1β signaling as new therapeutic modalities for these diseases

Reduction of Pulmonary Mast Cells in Areas of Acute Inflammation in Calves with Mannheimia (Pasteurella) haemolytica Pneumonia

Mast cells in the left cranial pulmonary lobe of colostrum-deprived neonatal calves were quantified 2 and 6 h after intrabronchial inoculation with Mannheimia (Pasteurella) haemolytica A1. The mast cells were detected (1) immunohistochemically with a mouse anti-human mast cell tryptase monoclonal antibody, and (2) by metachromatic staining with low pH toluidine blue. A greater number of mast cells was demonstrated by the second method than by the first. At 6 h after inoculation, but not at 2 h, the number of mast cells was significantly reduced at the site of the main lesions. Treatment of calves with a sialyl Lewis mimetic (TBC1269) did not appreciably affect the results at 6 h