title: High glucose induces the expression of osteopontin in blood vessels in vitro and in vivo.
abstract: Osteopontin (OPN) is involved in mineral metabolism and the inflammatory response while diabetes mellitus is associated with severe and extensive vascular calcification. Therefore, we speculated that OPN could be a key factor in the calcification and dysfunction of blood vessels exposed to high glucose. To identify the relationship between high glucose and OPN, we used high glucose medium to stimulate smooth muscle cells (SMCs) and vascular endothelial cells (VECs) in vitro and diabetic rats for in vivo analyses. As assessed by flow cytometry and western blots, SMC and VEC apoptosis levels increased with high glucose. Potassium and calcium uptake by cells were also increased with high glucose. These findings demonstrated the relationship between mineral metabolism and high glucose. Western blot and quantitative real time polymerase chain reaction analyses demonstrated that OPN increased in vitro with high glucose stimulation. The inflammatory factor ICAM1 and the inhibitory phosphorylation of endothelial nitric-oxide synthase (eNOS) (Thr495) were also upregulated by high glucose. In contrast, the anti-inflammatory factor Nrf2 and the activating phosphorylation of eNOS (Ser1177) were downregulated. Similar to the change of OPN, phosphorylated P38 was increased with high glucose. SB203580, an inhibitor of P38 phosphorylation, downregulated the expression of OPN and related inflammatory factors. Additionally, OPN was increased in the aortas and plasma of diabetic rats. In conclusion, our findings demonstrate that high glucose can induce the expression of OPN, which may be a key factor in the calcification and dysfunction of the vascular wall in diabetes.
authors.affiliation: Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Tianjia
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Leng
authors.initials: L
authors.lastname: Ni
authors.affiliation: Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Xinnong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Zhanqi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China. Electronic address: liucw@vip.sina.com.
authors.forename: Changwei
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C506895:SPP1 protein, human; D053495:Osteopontin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose
keywords: Blood vessel; Calcification; Diabetes; High glucose; Osteopontin