کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5944466 1172344 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Therapeutic ultrasound: Increased HDL-Cholesterol following infusions of acoustic microspheres and apolipoprotein A-I plasmids
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Therapeutic ultrasound: Increased HDL-Cholesterol following infusions of acoustic microspheres and apolipoprotein A-I plasmids
چکیده انگلیسی


- Sonoporation, via acoustic microspheres with ApoA-I pDNA, resulted in increased HDL-C.
- HDL-C therapy using localized, acoustic delivery is devoid of viral-mediated vectors.
- A novel therapeutic, gene delivery system was developed for hypo-alphalipoproteinemia.

BackgroundLow levels of HDL-C are an independent cardiovascular risk factor associated with increased premature cardiovascular death. However, HDL-C therapies historically have been limited by issues relating to immunogenicity, hepatotoxicity and scalability, and have been ineffective in clinical trials.ObjectiveWe examined the feasibility of using injectable acoustic microspheres to locally deliver human ApoA-I DNA plasmids in a pre-clinical model and quantify increased production of HDL-C in vivo.MethodsOur novel site-specific gene delivery system was examined in naïve rat model and comprised the following steps: (1) intravenous co-administration of a solution containing acoustically active microspheres (Optison™, GE Healthcare, Princeton, New Jersey) and human ApoA-I plasmids; (2) ultrasound verification of the presence of the microspheres within the liver vasculature; (3) External application of locally-directed acoustic energy, (4) induction of microsphere disruption and in situ sonoporation; (4) ApoA-I plasmid hepatic uptake; (5) transcription and expression of human ApoA-I protein; and (6) elevation of serum HDL-C.ResultsCo-administration of ApoA-I plasmids and acoustic microspheres, activated by external ultrasound energy, resulted in transcription and production of human ApoA-I protein and elevated serum HDL-C in rats (up to 61%; p-value < 0.05).ConclusionsHDL-C was increased in rats following ultrasound directed delivery of human ApoA-I plasmids by microsphere sonoporation. The present method provides a novel approach to promote ApoA-I synthesis and nascent HDL-C elevation, potentially permitting the use of a minimally-invasive ultrasound-based, gene delivery system for treating individuals with low HDL-C.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Atherosclerosis - Volume 241, Issue 1, July 2015, Pages 92-99
نویسندگان
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