title: Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice.
abstract: BACKGROUND
  Type 2 diabetes is associated with macro- and microvascular complications in man. Microvascular dysfunction affects both cardiac and renal function and is now recognized as a main driver of cardiovascular mortality and morbidity. However, progression of microvascular dysfunction in experimental models is often obscured by macrovascular pathology and consequently demanding to study. The obese type 2 diabetic leptin-deficient (ob/ob) mouse lacks macrovascular complications, i.e. occlusive atherosclerotic disease, and may therefore be a potential model for microvascular dysfunction. The present study aimed to test the hypothesis that these mice with an insulin resistant phenotype might display microvascular dysfunction in both coronary and renal vascular beds.
  
  
  RESULTS
  In this study we used non-invasive Doppler ultrasound imaging to characterize microvascular dysfunction during the progression of diabetes in ob/ob mice. Impaired coronary flow velocity reserve was observed in the ob/ob mice at 16 and 21 weeks of age compared to lean controls. In addition, renal resistivity index as well as pulsatility index was higher in the ob/ob mice at 21 weeks compared to lean controls. Moreover, plasma L-arginine was lower in ob/ob mice, while asymmetric dimethylarginine was unaltered. Furthermore, a decrease in renal vascular density was observed in the ob/ob mice.
  
  
  CONCLUSIONS
  In parallel to previously described metabolic disturbances, the leptin-deficient ob/ob mice also display cardiac and renal microvascular dysfunction. This model may therefore be suitable for translational, mechanistic and interventional studies to improve the understanding of microvascular complications in type 2 diabetes.
authors.affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Helena U
authors.initials: HU
authors.lastname: Westergren
authors.affiliation: CVMD iMED, AstraZeneca R&D Mölndal, Mölndal, Sweden.
authors.forename: Julia
authors.initials: J
authors.lastname: Grönros
authors.affiliation: CVMD iMED, AstraZeneca R&D Mölndal, Mölndal, Sweden.
authors.forename: Suvi E
authors.initials: SE
authors.lastname: Heinonen
authors.affiliation: CVMD iMED, AstraZeneca R&D Mölndal, Mölndal, Sweden.
authors.forename: Tasso
authors.initials: T
authors.lastname: Miliotis
authors.affiliation: CVMD iMED, AstraZeneca R&D Mölndal, Mölndal, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Jennbacken
authors.affiliation: CVMD iMED, AstraZeneca R&D Mölndal, Mölndal, Sweden.
authors.forename: Alan
authors.initials: A
authors.lastname: Sabirsh
authors.affiliation: CVMD iMED, AstraZeneca R&D Mölndal, Mölndal, Sweden.
authors.forename: Anette
authors.initials: A
authors.lastname: Ericsson
authors.affiliation: CVMD iMED, AstraZeneca R&D Mölndal, Mölndal, Sweden.
authors.forename: Ann-Cathrine
authors.initials: AC
authors.lastname: Jönsson-Rylander
authors.affiliation: Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Svedlund
authors.affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; CVMD iMED, AstraZeneca R&D Mölndal, Mölndal, Sweden; Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Gan
mesh_terms: D000818:Animals; D003326:Coronary Circulation; D003924:Diabetes Mellitus, Type 2 / Q000000981:diagnostic imaging* / Q000235:genetics; D017078:Laser-Doppler Flowmetry; D020738:Leptin / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D012079:Renal Circulation; D014463:Ultrasonography
chemical_list: D020738:Leptin