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Sortilin and Its Multiple Roles in Cardiovascular and Metabolic Diseases
Claudia Goettsch1, Mads Kjolby1, Elena Aikawa2
1From the Department of Internal Medicine I-Cardiology, RWTH Aachen University, Germany (C.G.); The Danish Research Institute of Translational Neuroscience, Nordic European Molecular Biology Laboratory Partnership for Molecular Medicine, Danish Diabetes Academy, Denmark (M.K.); Department of Biomedicine (M.K.) and Department of Cardiology (M.K.), Aarhus University, Denmark; and Center for Interdisciplinary Cardiovascular Sciences (E.A.) and Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine (E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Abstract:
Cardiovascular disease is a leading cause of morbidity and mortality in the Western world. Studies of sortilin's influence on cardiovascular and metabolic diseases goes far beyond the genome-wide association studies that have revealed an association between cardiovascular diseases and the 1p13 locus that encodes sortilin. Emerging evidence suggests a significant role of sortilin in the pathogenesis of vascular and metabolic diseases; this includes type II diabetes mellitus via regulation of insulin resistance, atherosclerosis through arterial wall inflammation and calcification, and dysregulated lipoprotein metabolism. Sortilin is also known for its functional role in neurological disorders. It serves as a key receptor for cytokines, lipids, and enzymes and participates in pathological cargo loading to and trafficking of extracellular vesicles. This article provides a comprehensive review of sortilin's contributions to cardiovascular and metabolic diseases but focuses particularly on atherosclerosis. We summarize recent clinical findings that suggest that sortilin may be a cardiovascular risk biomarker and also discuss sortilin as a potential drug target.
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