title: Increased aortic stiffness and attenuated lysyl oxidase activity in obesity.
abstract: OBJECTIVE
  One potential mechanism through which obesity exerts adverse effects on the vascular system is by increasing aortic stiffness, a change known to be predictive of increased cardiovascular mortality. The aim of this study was to investigate the pathophysiology that links obesity to aortic stiffening.
  
  
  RESULTS
  Obese (ob/ob) mice were used to examine physical, morphological, and molecular changes in the aorta in response to obesity. ob/ob mice had increased aortic pulse wave velocity and tissue rigidity. ob/ob aorta exhibited decreases of lysyl oxidase (LOX) activity and cross-linked elastin, and increases of elastin fragmentation and elastolytic activity. The aortas of ob/ob mice were surrounded by a significant amount of proinflammatory and pro-oxidative perivascular adipose tissue. In vitro studies revealed that the conditioned medium from differentiated adipocytes or the perivascular adipose tissue of ob/ob mice attenuated LOX activity. Furthermore, inhibition of LOX in wild-type lean mice caused elastin fragmentation and induced a significant increase in pulse wave velocity. Finally, we found that obese humans had stiffer arteries and lower serum LOX levels than do normal-weight humans.
  
  
  CONCLUSIONS
  Our results demonstrated that obesity resulted in aortic stiffening in both humans and mice, and established a causal relationship between LOX downregulation and aortic stiffening in obesity.
authors: Institute of Clinical Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors: Ju-Yi
authors: JY
authors: Chen
authors: Pei-Jane
authors: PJ
authors: Tsai
authors: Haw-Chih
authors: HC
authors: Tai
authors: Ruei-Lan
authors: RL
authors: Tsai
authors: Yu-Tzu
authors: YT
authors: Chang
authors: Mei-Chung
authors: MC
authors: Wang
authors: Yu-Wei
authors: YW
authors: Chiou
authors: Ming-Long
authors: ML
authors: Yeh
authors: Ming-Jer
authors: MJ
authors: Tang
authors: Chen-Fuh
authors: CF
authors: Lam
authors: Shu-Chu
authors: SC
authors: Shiesh
authors: Yi-Heng
authors: YH
authors: Li
authors: Wei-Chuan
authors: WC
authors: Tsai
authors: Chang-Hua
authors: CH
authors: Chou
authors: Li-Jen
authors: LJ
authors: Lin
authors: Hua-Lin
authors: HL
authors: Wu
authors: Yau-Sheng
authors: YS
authors: Tsai
mesh_terms: D017667:Adipocytes / Q000201:enzymology; D000273:Adipose Tissue / Q000201:enzymology; D000328:Adult; D000629:Aminopropionitrile / Q000494:pharmacology; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology*; D016022:Case-Control Studies; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D055119:Elastic Modulus; D004549:Elastin / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology*; D018384:Oxidative Stress; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D063177:Pulse Wave Analysis; D013997:Time Factors; D059289:Vascular Stiffness
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D000629:Aminopropionitrile; D004549:Elastin; D008249:Protein-Lysine 6-Oxidase