Gold nanoparticle-based miR155 antagonist macrophage delivery restores the cardiac function in ovariectomized diabetic mouse model.
Diabetic cardiomyopathy is a common disease in postmenopausal women, in whom the estrogen deficiency aggravates the pathology. In this study, we have found that estrogen deficiency due to ovariectomy aggravates the inflammation in the hearts of diabetic mice, as depicted by excessive proinflammatory type 1 macrophages (M1) over anti-inflammatory type 2 macrophages (M2). Accordingly, an additional increase of reactive oxygen species, cell apoptosis, cardiac hypertrophy, and fibrosis was observed in the hearts of ovariectomized diabetic mice, in comparison with the diabetes-only group. Significantly, miR155, a potent promoter of M1 polarization, was found to be additionally enhanced in the macrophages and hearts by ovariectomy. Tail vein injection of miR155-AuNP, in which thiol-modified antago-miR155 was covalently conjugated with gold nanoparticle (AuNP), preferentially delivered the nucleic acids into the macrophages via phagocytosis. Together with the increased M2 ratio and reduced inflammation, in vivo delivery of antago-miR155 reduced cell apoptosis and restored the cardiac function. The restoration efficacy of miR155-AuNP was much better than general macrophage depletion by clodrosome. In summary, we revealed that M1/M2 imbalance contributes to the aggravated cardiomyopathy in ovariectomized diabetic mice, and therapeutically reducing miR155 in macrophages by AuNP serves as a promising strategy in improving cardiac function.
['Jia|Chengming|C|', 'Chen|Hui|H|', 'Wei|Mengying|M|', 'Chen|Xiangjie|X|', 'Zhang|Yajun|Y|', 'Cao|Liang|L|', 'Yuan|Ping|P|', 'Wang|Fangyuan|F|', 'Yang|Guodong|G|', 'Ma|Jing|J|']
D000818:Animals D017209:Apoptosis D003921:Diabetes Mellitus, Experimental D058065:Diabetic Cardiomyopathies D016503:Drug Delivery Systems D005260:Female D005355:Fibrosis D006046:Gold D008264:Macrophages D008810:Mice, Inbred C57BL D035683:MicroRNAs D009205:Myocarditis D009206:Myocardium D053758:Nanoparticles D010052:Ovariectomy
miR155 macrophage cardiac function ovariectomized diabetic mouse model gold nanoparticle targeted delivery