1. Prevent diabetic cardiomyopathy in diabetic rats by combined therapy of aFGF-loaded nanoparticles and ultrasound-targeted microbubble destruction technique.
- Author
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Zhao YZ, Zhang M, Wong HL, Tian XQ, Zheng L, Yu XC, Tian FR, Mao KL, Fan ZL, Chen PP, Li XK, and Lu CT
- Subjects
- Animals, Apoptosis drug effects, Coronary Circulation drug effects, Diabetes Mellitus, Experimental metabolism, Diabetes Mellitus, Experimental physiopathology, Diabetic Cardiomyopathies metabolism, Diabetic Cardiomyopathies physiopathology, Fibroblast Growth Factor 1 pharmacology, Fibroblast Growth Factor 1 therapeutic use, Heart physiopathology, Male, Mice, Microvessels drug effects, Myocardium pathology, NIH 3T3 Cells, Nanoparticles therapeutic use, Proto-Oncogene Proteins c-akt metabolism, Rats, Sprague-Dawley, Ventricular Dysfunction, Left drug therapy, Ventricular Dysfunction, Left metabolism, Ventricular Dysfunction, Left physiopathology, Diabetes Mellitus, Experimental drug therapy, Diabetic Cardiomyopathies prevention & control, Fibroblast Growth Factor 1 administration & dosage, Microbubbles, Nanoparticles administration & dosage, Ultrasonic Waves
- Abstract
Acidic fibroblast growth factor (aFGF) has shown the great potential to prevent the structural and functional injuries caused by diabetic cardiomyopathy (DCM). The present study sought to investigate the preclinical performance and mechanism of the combination therapy of aFGF-nanoparticles (aFGF-NP) and ultrasound-targeted microbubble destruction (UTMD) technique for DCM prevention. From Mason staining and TUNEL staining, aFGF-NP+UTMD group showed significant differences from the diabetes group and other groups treated with aFGF or aFGF-NP. The cardiac collagen volume fraction (CVF) and cardiac myocyte apoptosis index in aFGF-NP+UTMD group reduced to 4.15% and 2.31% respectively, compared with those in the diabetes group (20.5% and 11.3% respectively). Myocardial microvascular density (MCD) in aFGF-NP+UTMD group was up to 35n/hpf, much higher than that in the diabetes group (14n/hpf). The diabetes group showed similar results (MCD, CVF and cardiac myocyte apoptosis index) to other aFGF treatment groups (free aFGF±UTMD or aFGF-NP). Indexes from transthoracic echocardiography and hemodynamic evaluation also proved the same conclusion. These results confirmed that the abnormalities including diastolic dysfunctions, myocardial fibrosis and metabolic could be suppressed by the different extents of twice weekly aFGF treatments for 12 consecutive weeks (free aFGF or aFGF-NP±UTMD), with the strongest improvements observed in the aFGF-NP+UTMD group. Western blot and immunohistochemical analyses of heart tissue samples further revealed the high efficiency of heart-targeted delivery and effective cardioprotection with this combination approach. Overall, this study has generated supportive data that are critical for the translation of a promising DCM prevention strategy., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2016
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