title: Soluble receptor for advanced glycation end products mitigates vascular dysfunction in spontaneously hypertensive rats.
abstract: Vascular dysfunction including vascular remodeling and endothelial dysfunction in hypertension often results in poor clinical outcomes and increased risk of vascular accidents. We investigate the effect of treatment with soluble receptor for advanced glycation end products (sRAGE) on vascular dysfunction in spontaneously hypertensive rats (SHR). Firstly, the aortic AGE/RAGE pathway was investigated in SHR. Secondly, SHR received intraperitoneal injections of sRAGE daily for 4 weeks. Effect of sRAGE against vascular dysfunction in SHR and underlying mechanism was investigated. SHR aortas exhibited enhanced activity of aldose reductase, reduced activity of glyoxalase 1, accumulation of methylglyoxal and AGE, and upregulated expression of RAGE. Treatment of SHR with sRAGE had no significant effect on blood pressure, but alleviated aortic hypertrophy and endothelial dysfunction. In vitro, treatment with sRAGE reversed the effect of incubation with AGE on proliferation of smooth muscle cells and endothelial function. Treatment of SHR with sRAGE abated oxidative stress, suppressed inflammation and NF-κB activation, improved the balance between Ang II and Ang-(1-7) through reducing angiotensin-converting enzyme (ACE) activity and enhancing ACE2 expression, and upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in aortas. In conclusion, treatment with sRAGE alleviated vascular adverse remodeling in SHR, possibly via suppression of oxidative stress and inflammation, improvement in RAS balance, and activation of PPAR-γ pathway.
authors.affiliation: Department of Cardiology, Jinling Hospital, Nanjing University, Zhongshan East Road 305, Nanjing, 210002, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Manli
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai, China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, The 455th Hospital of PLA, Shanghai, China.
authors.forename: Qingxin
authors.initials: Q
authors.lastname: Cao
authors.affiliation: OutPatient Department, The 455th Hospital of PLA, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Medical Statistics, Jinling Hospital, Nanjing University, Zhongshan East Road 305, Nanjing, 210002, China.
authors.forename: Yuxiu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Jinling Hospital, Nanjing University, Zhongshan East Road 305, Nanjing, 210002, China. gongjb2014@hotmail.com.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Gong
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000378:metabolism; D007791:Lactoylglutathione Lyase / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D047495:PPAR gamma / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D066253:Vascular Remodeling / Q000187:drug effects*
chemical_list: C000593874:Ager protein, rat; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D047495:PPAR gamma; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D007791:Lactoylglutathione Lyase; C118790:angiotensin I (1-7)
keywords: Inflammation; Oxidative stress; Soluble receptor for advanced glycation end products; Spontaneously hypertensive rats; Vascular dysfunction