title: Cardiac fibrosis and vascular remodeling are attenuated by metformin in obese rats.
abstract: BACKGROUND
  Human obesity has been associated with alterations of vascular structure, especially in large and medium arteries, but the effects of insulin-sensitizers are not well known.
  
  
  METHODS
  Twenty-five male Wistar rats received subcutaneous injections of monosodium glutamate (MSG) or an equivalent volume of vehicle from the second to the sixth day after birth, At 16 weeks of age, five MSG rats started receiving an oral treatment with metformin (300 mg/kg) which was maintained for six weeks, composing five groups: control 16 weeks (CON-16), MSG 16 weeks (MSG-16), control 22 weeks (CON-22), MSG 22 weeks (MSG-22), and MSG plus metformin 22 weeks (MET-22). Systolic blood pressure (BP) was verified weekly. The lumen diameter and media thickness, media cross-sectional area (CSA) and growth index of the intramyocardial arterioles were measured. Cardiac interstitial and perivascular collagen density were also evaluated.
  
  
  RESULTS
  Systolic BP was significantly increased in the MSG-22 comparing to MSG-16 group. Insulin resistance was confirmed by HOMA-IR index and metformin-treated group presented reduction of insulin levels at week 22. The morphology analysis showed greater media-to-lumen ratio and CSA in the obese groups, which were reduced by the metformin treatment. Connective tissue deposition in the perivascular region of the left ventricle was significantly higher in the obese groups which was attenuated by metformin.
  
  
  CONCLUSIONS
  Hypertrophic vascular remodeling and cardiac collagen deposition were significantly evident in MSG-induced obese rats. Metformin treatment was able to reduce insulin resistance and attenuated this adverse cardiac and vascular remodeling.
authors.affiliation: Department of Clinical Medicine, Biomedical Centre, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Adriana K
authors.initials: AK
authors.lastname: Burlá
authors.forename: Núbia S
authors.initials: NS
authors.lastname: Lobato
authors.forename: Zuleica B
authors.initials: ZB
authors.lastname: Fortes
authors.forename: Wille
authors.initials: W
authors.lastname: Oigman
authors.forename: Mario Fritsch
authors.initials: MF
authors.lastname: Neves
mesh_terms: D000818:Animals; D004719:Endomyocardial Fibrosis / Q000473:pathology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D009765:Obesity / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin