title: Effects of a new advanced glycation inhibitor, LR-90, on mitigating arterial stiffening and improving arterial elasticity and compliance in a diabetic rat model: aortic impedance analysis.
abstract: OBJECTIVE
  We determined the effects of treatment with LR-90, an inhibitor of advanced glycation end products, on the mechanical properties of the arterial system in streptozotocin (STZ)-induced diabetic Sprague Dawley rats, using aortic impedance analysis, and further investigated the effects of LR-90 on the progression of aortic pathology.
  
  
  METHODS
  STZ-induced diabetic rats were treated with or without LR-90 (50 mg L(-1) in drinking water) for 8 weeks and compared with control groups. Arterial BP measurements, various metabolic parameters, aortic histopathology, collagen cross-linking, AGE accumulation, and RAGE protein expression in aortic tissue were determined. Pulsatile parameters were evaluated using a standard Fourier series expansion technique and impulse response function of the filtered aortic input impedance spectra.
  
  
  RESULTS
  LR-90 reduced glycated haemoglobin and triglycerides levels, although it had no effect on the glycaemic status. LR-90 did not affect arterial BP, but prevented the diabetes-induced increase in peripheral resistance and variations in aortic distensibility, as it reduced aortic characteristic impedance by 21%. LR-90 also prevented the elevation in wave reflection factor, as indicated by a 22.5% reduction and an associated increase of 23.5% in wave transit time, suggesting it prevents the augmentation of the systolic load of the left ventricle. Moreover, LR-90 inhibited collagen cross-linking and the accumulation of AGE and RAGE in the vasculature of diabetic rats.
  
  
  CONCLUSIONS
  Treatment with LR-90 may impart significant protection against diabetes-induced aortic stiffening and cardiac hypertrophy and provides an additional therapeutic option for treatment of AGE associated diabetic complications.
authors.affiliation: Division of Comparative Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Satheesan
authors.forename: J L
authors.initials: JL
authors.lastname: Figarola
authors.forename: T
authors.initials: T
authors.lastname: Dabbs
authors.forename: S
authors.initials: S
authors.lastname: Rahbar
authors.forename: R
authors.initials: R
authors.lastname: Ermel
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D006332:Cardiomegaly / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control; D003094:Collagen / Q000378:metabolism; D003187:Compliance; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D002087:Butyrates; D003094:Collagen; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014280:Triglycerides; C485003:LR-90
keywords: Advanced glycation end products; LR-90; aortic characteristic impedance; aortic distensibility; wave reflection factor; wave transit time