title: Assessment of cardiac inflammation and remodeling during the development of streptozotocin-induced diabetic cardiomyopathy in vivo: a time course analysis.
abstract: In this study, we examined cardiac inflammation, fibrosis and left ventricular (LV) function during the development of streptozotocin (STZ)-induced diabetic cardiomyopathy using an animal model of diabetes mellitus (DM). Diabetes was induced in 22 Sprague‑Dawley rats by an intraperitoneal single injection of STZ (70 mg/kg). Non-diabetic animals served as the controls (n=6). LV function was documented using the conductance catheter technique 2 and 6 weeks after the induction of diabetes. Cardiac tissue was analyzed for cardiac immune cell infiltration, oxidative stress and remodeling in rats with STZ-induced diabetes at 2 different time points by immunohistochemistry. Cardiac function was significantly impaired in the diabetic animals. After 2 weeks, the induction of diabetes resulted in impaired cardiac function indexed by a decrease in systolic and diastolic LV function. This impairment of LV performance continued for up to 6 weeks after the STZ injection. This was associated with an increase in cardiac CD3+ and CD8a+ immune cell invasion and fibrosis, indexed by an increase in collagen content (p<0.05). Furthermore, oxidative stress response and matrix remodeling were increased after 2 weeks and this continued for up to 6 weeks after the induction of diabetes. In conclusion, cardiac dysfunction is associated with cardiac inflammation and adverse remodeling in experimental diabetic cardiomyopathy. Our results suggest that the model of STZ-induced diabetic cardiomyopathy is a robust model for investigating cardiac immune response and LV remodeling processes under diabetic conditions.
authors: Department of Cardiology and Pneumology, Charité University Hospital Berlin, Campus Benjamin Franklin, D-12200 Berlin, Germany.
authors: P M
authors: PM
authors: Becher
authors: D
authors: D
authors: Lindner
authors: M
authors: M
authors: Fröhlich
authors: K
authors: K
authors: Savvatis
authors: D
authors: D
authors: Westermann
authors: C
authors: C
authors: Tschöpe
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D003921:Diabetes Mellitus, Experimental; D058065:Diabetic Cardiomyopathies / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis; D006439:Hemodynamics; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D018384:Oxidative Stress; D051381:Rats; D013311:Streptozocin / Q000009:adverse effects*; D013997:Time Factors; D020257:Ventricular Remodeling
chemical_list: D000903:Antibiotics, Antineoplastic; D013311:Streptozocin