Pluronic® L64-mediated stable HIF-1α expression in muscle for therapeutic angiogenesis in mouse hindlimb ischemia

نویسندگان

  • Hongmei Song
  • Sijia Liu
  • Caixia Li
  • Yanyan Geng
  • Gang Wang
  • Zhongwei Gu
چکیده

Intramuscular injection of plasmid DNA (pDNA) to express a therapeutic protein is a promising method for the treatment of many diseases. However, the therapeutic applications are usually hindered by gene delivery efficiency and expression level. In this study, critical factors in a pDNA-based gene therapy system, such as gene delivery materials, a therapeutic gene, and its regulatory elements, were optimized to establish an integrated system for the treatment of mouse hindlimb ischemia. The results showed that Pluronic L64 (L64) was an efficient and safe material for gene delivery into mouse skeletal muscle. It also showed intrinsic ability to promote in vivo angiogenesis in a concentration-dependent manner, which might be through the activation of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB)-regulated angiogenic factors. The combination of 0.1% L64 with a hybrid gene promoter (pSC) increased the gene expression level, elongated the gene expression duration, and enhanced the number of transfected muscle fibers. In mice ischemic limbs, a gene medicine (pSC-HIF1α(tri)/L64) composed of L64 and pSC-based expression plasmid encoding hypoxia-inducible factor 1-alpha triple mutant (HIF-1α(tri)), improved the expression of stable HIF-1α, and in turn, the expression of multiple angiogenic factors. As a result, the ischemic limbs showed accelerated function recovery, reduced foot necrosis, faster blood reperfusion, and higher capillary density. These results indicated that the pSC-HIF1α(tri)/L64 combination presented a potential and convenient venue for the treatment of peripheral vascular diseases, especially critical limb ischemia.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Hydrogen sulfide improves vessel formation of the ischemic adductor muscle and wound healing in diabetic db/db mice

Objective(s): It has been demonstrated that hydrogen sulfide plays a vital role in physiological and pathological processes such as regulating inflammation, oxidative stress, and vessel relaxation. The aim of the study was to explore the effect of hydrogen sulfide on angiogenesis in the ischemic adductor muscles of type 2 diabetic db/db mice and ischemic diabetic wound...

متن کامل

Effect of pioglitazone on expression of hypoxia-inducible factor 1α and vascular endothelial growth factor in ischemic hindlimb of diabetic rats.

OBJECTIVE To observe effects of the drug pioglitazone on expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in diabetic rats with hindlimb ischemia, and explore the role of pioglitazone in angiogenesis after ischemia and its possible mechanism. MATERIALS AND METHODS The diabetic rat model was established by high-fat and high-sugar diet and intrape...

متن کامل

Triiodothyronine potentiates angiogenesis-related factor expression through PI3K/AKT signaling pathway in human osteoarthritic osteoblasts

Objective(s): Previous study has indicated that triiodothyronine (T3) facilitated cartilage degeneration in osteoarthritis (OA). This study aimed to investigate the effects of T3 on angiogenesis-related factor expression in human osteoblasts of OA subchondral bone.Materials and Methods: The subchondral bone specimens were obtained from O...

متن کامل

Hypoxia-Inducible factor-1α promotes neuroregeneration and angiogenesis after cerebral ischemia

To promote neuroregeneration and angiogenesis is a therapeutic target for the treatment of stroke. Hypoxia-inducible factor-1α (HIF-1α) has pleiotropic effects on neurogenesis, angiogenesis and neuroprotection in central nervous system. In this study we investigated whether HIF-1α treatment promotes the proliferation of ischemia induced neural stem cells (NSCs) and neuroregeneration in penumbra...

متن کامل

The effects of 8 weeks aerobic training on HIF-1α, miR-21 and VEGF gene expression in female Balb/c with breast cancer

Background: Breast cancer, which is a major cancer for women, affects the angiogenesis process. Exercise training can decrease the process of angiogenesis in tumor tissue. The aim of present study was to investigate the effects of 8 weeks of aerobic training on HIF-1α, miR-21 and VEGF gene expression in female Balb/c mice with breast cancer. Materials and Methods: 16 female Balb/c mice (age: 3...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 9  شماره 

صفحات  -

تاریخ انتشار 2014