Nerve growth factor gene therapy using adeno-associated viral vectors prevents cardiomyopathy in type 1 diabetic mice.
Nerve growth factor gene therapy using adeno-associated viral vectors prevents cardiomyopathy in type 1 diabetic mice.
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DOI：
10.2337/db11-0763
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发表时间：
2012-01
期刊：
影响因子：
7.7
通讯作者：
Emanueli C
中科院分区：
文献类型：
--
作者：
Meloni M;Descamps B;Caporali A;Zentilin L;Floris I;Giacca M;Emanueli C
糖尿病是心脏功能障碍、心肌灌注减少和最终心力衰竭的原因。神经生长因子（NGF）对心血管系统具有保护作用。本研究旨在探讨神经生长因子基因转移是否能预防小鼠糖尿病心肌病。我们研究了链脲佐菌素诱导的1型糖尿病小鼠和非糖尿病对照小鼠。在确定糖尿病降低心脏NGFmRNA表达后，我们测试了用腺相关病毒载体（AAV）进行的NGF基因疗法保护糖尿病小鼠心脏的能力。为此，在糖尿病2周后，通过心肌内注射AAV血清型2（AAV 2）或全身递送AAV血清型9（AAV 9）诱导人NGF或β-Gal（对照）基因的心脏表达。给予非糖尿病小鼠AAV 2-β-Gal或AAV 9-β-Gal。我们发现通过AAV 2或AAV 9接受NGF基因转移的糖尿病小鼠避免了在注射β-Gal的糖尿病小鼠中观察到的心脏功能进行性恶化和左心室腔扩大。此外，它们还受到保护，免受心肌微血管稀疏、灌注不足、间质纤维化沉积增加以及内皮细胞和心肌细胞凋亡增加的影响，这些影响了β-Gal注射的糖尿病对照小鼠。我们的数据表明NGF在预防糖尿病受试者心肌病方面具有治疗潜力。
Diabetes is a cause of cardiac dysfunction, reduced myocardial perfusion, and ultimately heart failure. Nerve growth factor (NGF) exerts protective effects on the cardiovascular system. This study investigated whether NGF gene transfer can prevent diabetic cardiomyopathy in mice. We worked with mice with streptozotocin-induced type 1 diabetes and with nondiabetic control mice. After having established that diabetes reduces cardiac NGF mRNA expression, we tested NGF gene therapies with adeno-associated viral vectors (AAVs) for the capacity to protect the diabetic mouse heart. To this aim, after 2 weeks of diabetes, cardiac expression of human NGF or β-Gal (control) genes was induced by either intramyocardial injection of AAV serotype 2 (AAV2) or systemic delivery of AAV serotype 9 (AAV9). Nondiabetic mice were given AAV2–β-Gal or AAV9–β-Gal. We found that the diabetic mice receiving NGF gene transfer via either AAV2 or AAV9 were spared the progressive deterioration of cardiac function and left ventricular chamber dilatation observed in β-Gal–injected diabetic mice. Moreover, they were additionally protected from myocardial microvascular rarefaction, hypoperfusion, increased deposition of interstitial fibrosis, and increased apoptosis of endothelial cells and cardiomyocytes, which afflicted the β-Gal–injected diabetic control mice. Our data suggest therapeutic potential of NGF for the prevention of cardiomyopathy in diabetic subjects.
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DOI：
10.1161/circheartfailure.109.903450
发表时间：
2010-03
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Katare RG;Caporali A;Oikawa A;Meloni M;Emanueli C;Madeddu P
通讯作者：
Madeddu P
影响因子：
37.8
作者：
Emanueli, C;Salis, MB;Mededdu, P
通讯作者：
Mededdu, P
DOI：
10.1111/j.1749-6632.1964.tb33978.x
发表时间：
1964-01-01
影响因子：
5.2
作者：
LEVIMONTALCINI, R
通讯作者：
LEVIMONTALCINI, R
影响因子：
37.8
作者：
Ieda, Masaki;Kanazawa, Hideaki;Fukuda, Keiichi
通讯作者：
Fukuda, Keiichi
影响因子：
37.8
作者：
Emanueli, C;Salis, MB;Madeddu, P
通讯作者：
Madeddu, P