Chronic type 1 diabetes in spontaneously hypertensive rats leads to exacerbated cardiac fibrosis.
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.
Black
Mary Jane
MJ
Department of Anatomy and Developmental Biology, Monash University, Victoria, Australia. jane.black@med.monash.edu.au
D'Amore
Angelo
A
Auden
Alana
A
Stamp
Laura
L
Osicka
Tanya
T
Panagiotopoulos
Sianna
S
Jerums
George
G
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
D000199:Actins; D024042:Collagen Type I; D024061:Collagen Type III; C498862:Acta2 protein, rat