Abstract 14341: Targeted Delivery of Fibroblast Growth Factor-1 by Ultrasound-targeted Microbubble Destruction Reduces Myocyte Apoptosis and Myocardial Fibrosis and Improves Ventricular Systolic and Diastolic Function in Diabetic Cardiomyopathy in Rats
We sought to pursue the hypothesis that fibroblast growth factor-1 (FGF-1) facilitates tissue repair, angiogenesis, and cardiac functional improvement in diabetic cardiomyopathy (DCM) by targeted delivery of FGF-1 using an ultrasound-targeted microbubble destruction (UTMD) strategy.
METHODS: A total of 60 SD rats were randomized into 5 groups. DCM was induced by intra-peritoneal injection of streptozotocin. Targeted delivery of FGF-1 was achieved by intravenous injection of FGF-1, SonoVue (Bracco Diagnostics Inc. Princeton, NJ) and simultaneous transthoracic ultrasound irradiation of the myocardium. Group assignments were: Group 1 (Control), Group 2 (DCM/no treatment), Group 3 (DCM/FGF-1 only); Group 4 (DCM/FGF-1+SonoVue only), and Group 5 (DCM/FGF-1+SonoVue+ultrasound irradiation). Four weeks after treatment, the animals were evaluated by transthoracic echocardiography for left ventricular (LV) fractional shortening (FS), catheterization for LV end-diastolic pressure (LVEDP) and dp/dtmax; Masson staining for quantification of myocardial collagen volume fraction (CVF), and TUNEL for analysis of myocardial apoptosis index (AI).
RESULTS: Compared with Group 1 (Control), Group 2-5 showed significant LV systolic dysfunction (P<0.05) after streptozotocin and before FGF-1/UTMD treatment. Table summarizes that FGF-1/UTMD treatment (Group 5), but not FGF-1 (Group 3) or FGF-1 + SonoVue (Group 4) alone, was associated with a significant improvement (P<0.05) in LVFS, LVEDP, ±dp/dtmax, AI, and CVF, respectively, compared with DCM (Group 2), although these measurements were significantly different from normal control (Group 1) 4 weeks after UTMD treatment.
CONCLUSIONS: Targeted FGF-1 delivery by UTMD significantly reduces cardiomyocyte apoptosis and myocardial fibrosis, and improves left ventricular systolic and diastolic function in DCM. This approach may provide a new preventive and therapeutic strategy for DCM.
- © 2013 by American Heart Association, Inc.