Coagulation Factor Xa and Protease-Activated Receptor 2 as Novel Therapeutic Targets for Diabetic Nephropathy

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 36; no. 8; pp. 1525 - 1533
• Main Authors: Oe, Yuji, Hayashi, Sakiko, Fushima, Tomofumi, Sato, Emiko, Kisu, Kiyomi, Sato, Hiroshi, Ito, Sadayoshi, Takahashi, Nobuyuki
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.08.2016
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Blood Coagulation - drug effects; Cell Line; Cytokines - genetics; Cytokines - metabolism; Diabetic Nephropathies - genetics; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Diabetic Nephropathies - prevention & control; Disease Models, Animal; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Factor Xa - drug effects; Factor Xa - genetics; Factor Xa - metabolism; Factor Xa Inhibitors - pharmacology; Genotype; Humans; Inflammation Mediators - metabolism; Insulin - genetics; Kidney Glomerulus - drug effects; Kidney Glomerulus - metabolism; Kidney Glomerulus - pathology; Macrophages - drug effects; Macrophages - metabolism; Male; Mice, Knockout; Nitric Oxide Synthase Type III - deficiency; Nitric Oxide Synthase Type III - genetics; Phenotype; Podocytes - drug effects; Podocytes - metabolism; Pyridines - pharmacology; Receptor, PAR-2 - antagonists & inhibitors; Receptor, PAR-2 - deficiency; Receptor, PAR-2 - genetics; Receptor, PAR-2 - metabolism; Signal Transduction - drug effects; Thiazoles - pharmacology; Up-Regulation; cardiovascular diseases; factor Xa; inflammation; prognosis; diabetic nephropathy

OBJECTIVE—The role of hypercoagulability in the pathogenesis of diabetic nephropathy (DN) remains elusive. We recently reported the increased infiltration of macrophages expressing tissue factor in diabetic kidney glomeruli; tissue factor activates coagulation factor X (FX) to FXa, which in turn sti...