title: Cardiac-targeting magnetic lipoplex delivery of SH-IGF1R plasmid attenuate norepinephrine-induced cardiac hypertrophy in murine heart.
abstract: Recent studies have demonstrated a number of molecular mechanisms contributing to the initiation of cardiac hypertrophy response to pressure overload. IGF1R (insulin-like growth factor-1 receptor), an important oncogene, is overexpressed in hypertrophic heart and mediates the hypertrophic pathology process. In this study, we applied with liposomal magnetofection that potentiated gene transfection by applying an external magnetic field to enhance its transfection efficiency. Liposomal magnetofection provided high efficiency in transgene expression in vivo. In vivo, IGF1R-specific-shRNA (small-hairpin RNA) by magnetofection inhibited IGF1R protein expression by 72.2 ± 6.8, 80.7 ± 9.6 and 84.5 ± 5.6%, at 24, 48 and 72 h, respectively, after pGFPshIGF1R injection, indicating that liposomal magnetofection is a promising method that allows the targeting of gene therapy for heart failure. Furthermore, we found that the treated animals (liposomal magnetofection with shIGF1R) showed reduced septal and posterior wall thickness, reduced HW:BWs (heart weight-to-body weights) compared with controls. Moreover, we also found that liposomal magnetofection-based shIGF1R transfection decreased the expression level of p-ERK (phosphorylated extracellular-signal-regulated kinase)1/2, p-AKT1 (phosphorylated protein kinase B1) compared with untreated hearts. These results suggested that liposomal magnetofection-mediated IGF1R-specific-shRNA may be a promising method, and suppression the IGF1R expression inhibited norepinephrine-induced cardiac hypertrophic process via inhibiting PI3K (phosphoinositide 3-kinase)/AKT pathway.
authors: *Children' Hospital Zhejiang University School of Medicine Hangzhou 310003, China.
authors: Yiping
authors: Y
authors: Xu
authors: †Cardiothoracic Surgery, Department of Second Affiliated Hospital, School of Medicine, Zhejiang University, Number 88, Jie Fang Road, Hang Zhou, Zhejiang Province 310009, China.
authors: Xuebiao
authors: X
authors: Li
authors: †Cardiothoracic Surgery, Department of Second Affiliated Hospital, School of Medicine, Zhejiang University, Number 88, Jie Fang Road, Hang Zhou, Zhejiang Province 310009, China.
authors: Minjian
authors: M
authors: Kong
authors: †Cardiothoracic Surgery, Department of Second Affiliated Hospital, School of Medicine, Zhejiang University, Number 88, Jie Fang Road, Hang Zhou, Zhejiang Province 310009, China.
authors: Daming
authors: D
authors: Jiang
authors: †Cardiothoracic Surgery, Department of Second Affiliated Hospital, School of Medicine, Zhejiang University, Number 88, Jie Fang Road, Hang Zhou, Zhejiang Province 310009, China.
authors: Aiqiang
authors: A
authors: Dong
authors: †Cardiothoracic Surgery, Department of Second Affiliated Hospital, School of Medicine, Zhejiang University, Number 88, Jie Fang Road, Hang Zhou, Zhejiang Province 310009, China.
authors: Zhonghua
authors: Z
authors: Shen
authors: †Cardiothoracic Surgery, Department of Second Affiliated Hospital, School of Medicine, Zhejiang University, Number 88, Jie Fang Road, Hang Zhou, Zhejiang Province 310009, China.
authors: Qunjun
authors: Q
authors: Duan
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D018014:Gene Transfer Techniques; D008081:Liposomes; D060526:Magnetic Fields; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000009:adverse effects* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases; D010957:Plasmids / Q000235:genetics / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014662:Vasoconstrictor Agents / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D008081:Liposomes; D034741:RNA, Small Interfering; D014662:Vasoconstrictor Agents; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D009638:Norepinephrine