Pulmonary hypertension (PH) is a multifaceted vascular disease where development and severity are determined by both genetic and environmental factors. Over the past decade, there has been an acceleration of the discovery of molecular effectors that mediate PH pathogenesis, including large numbers of microRNA molecules that are expressed in pulmonary vascular cell types and exert system-wide regulatory functions in all aspects of vascular health and disease. Due to the inherent pleiotropy, overlap, and redundancy of these molecules, it has been challenging to define their integrated effects on overall disease manifestation. In this review, we summarize our current understanding of the roles of microRNAs in PH with an emphasis on potential methods to discern the hierarchical motifs governing their multifunctional and interconnected activities. Deciphering this higher order of regulatory structure will be crucial for overcoming the challenges of developing these molecules as biomarkers or therapeutic targets, in isolation or combination.
Vinny Negi, Stephen Y. Chan
Despite the rising incidence of autoimmunity, therapeutic options for patients with autoimmune disease still rely on decades-old immunosuppressive strategies that risk severe and potentially fatal complications. Thus, novel therapeutic approaches for autoimmune diseases are greatly needed in order to minimize treatment-related toxicity. Such strategies would ideally target only the autoreactive immune components to preserve beneficial immunity. Here, we review how several decades of basic, translational, and clinical research on the immunology of pemphigus vulgaris (PV), an autoantibody-mediated skin disease, have enabled the development of targeted immunotherapeutic strategies. We discuss research to elucidate the pathophysiology of PV and how the knowledge afforded by these studies has led to the preclinical and clinical testing of targeted approaches to neutralize autoantibodies, to induce antigen-specific tolerance, and to specifically eliminate autoreactive B cells in PV.
Christoph T. Ellebrecht, Aimee S. Payne
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