title: Chronic type 1 diabetes in spontaneously hypertensive rats leads to exacerbated cardiac fibrosis.
abstract: BACKGROUND
  Diabetes in human subjects is often associated with hypertension. The aim of this study was to examine the development of cardiac fibrosis following induction of type 1 diabetes in genetically hypertensive rats.
  
  
  METHODS
  Diabetes was induced by streptozotocin (STZ) injection in 8-week-old normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) for a duration of 16 or 24 weeks. Aged-matched, nondiabetic WKY and SHRs were used as controls. At termination of treatment, the rats were anaesthetized, hearts arrested in diastole and perfusion fixed. A comprehensive examination of cardiac fibrosis throughout the right and left ventricles was undertaken in picrosirius red-stained sections, using image analysis and by undertaking collagen type I and type III immunohistochemistry.
  
  
  RESULTS
  Induction of diabetes in the SHRs led to a marked increase in the levels of interstitial fibrosis in the left ventricle plus septum (LV+S) at both 16 and 24 weeks duration (59% and 43% increase, respectively) and also in the right ventricle after 24 weeks duration of diabetes (35% increase compared to the nondiabetic SHR). Exacerbated perivascular fibrosis was also observed in the LV+S in the diabetic-hypertensive rats at the later time point. These effects of induction of diabetes were not observed in the normotensive strain.
  
  
  CONCLUSIONS
  Our findings clearly demonstrate elevations in cardiac fibrosis when type 1 diabetes is combined with hypertension. Our findings thus stress the importance of closely monitoring both blood pressure and glucose levels in type 1 diabetic patients in order to prevent myocardial collagen deposition.
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Victoria, Australia. jane.black@med.monash.edu.au
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Black
authors.forename: Angelo
authors.initials: A
authors.lastname: D'Amore
authors.forename: Alana
authors.initials: A
authors.lastname: Auden
authors.forename: Laura
authors.initials: L
authors.lastname: Stamp
authors.forename: Tanya
authors.initials: T
authors.lastname: Osicka
authors.forename: Sianna
authors.initials: S
authors.lastname: Panagiotopoulos
authors.forename: George
authors.initials: G
authors.lastname: Jerums
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003331:Coronary Vessels / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005355:Fibrosis; D006331:Heart Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors
chemical_list: D000199:Actins; D024042:Collagen Type I; D024061:Collagen Type III; C498862:Acta2 protein, rat