title: Glycosaminoglycan overproduction in the aorta increases aortic calcification in murine chronic kidney disease.
abstract: BACKGROUND
  Vascular calcification accompanying chronic kidney disease increases the mortality and morbidity associated with cardiovascular disorders, but no effective therapy is available. We hypothesized that glycosaminoglycans may contribute to osteoblastic differentiation of vascular smooth muscle cells during vascular calcification.
  
  
  RESULTS
  We used exostosin-like glycosyltranferase 2-deficient (EXTL2 knockout) mice expressing high levels of glycosaminoglycans in several organs including the aorta. We performed 5/6 subtotal nephrectomy and fed the mice a high-phosphate diet to induce chronic kidney disease. Overexpression of glycosaminoglycans in the aorta enhanced aortic calcification in chronic kidney disease in EXTL2 knockout mice. Ex vivo and in vitro, matrix mineralization in aortic rings and vascular smooth muscle cells of EXTL2 knockout mice was augmented. Furthermore, removal of glycosaminoglycans in EXTL2 knockout and wild-type mice-derived vascular smooth muscle cells effectively suppressed calcium deposition in a high-phosphate environment.
  
  
  CONCLUSIONS
  These results illustrate an important role for glycosaminoglycans in the development of vascular calcification. Manipulation of glycosaminoglycan expression may have beneficial effects on the progression of vascular calcification in chronic kidney disease patients.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Eko
authors.initials: E
authors.lastname: Purnomo
authors.forename: Noriaki
authors.initials: N
authors.lastname: Emoto
authors.forename: Dwi Aris Agung
authors.initials: DA
authors.lastname: Nugrahaningsih
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakayama
authors.forename: Keiko
authors.initials: K
authors.lastname: Yagi
authors.forename: Susi
authors.initials: S
authors.lastname: Heiden
authors.forename: Satomi
authors.initials: S
authors.lastname: Nadanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001018:Aortic Diseases / Q000209:etiology*; D002454:Cell Differentiation; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D010006:Osteoblasts / Q000166:cytology; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000378:metabolism*; D061205:Vascular Calcification / Q000209:etiology*
chemical_list: D006025:Glycosaminoglycans
keywords: chondroitin sulfate; chronic kidney disease; glycosaminoglycan; heparan sulfate; vascular calcification