Therapeutic ultrasound: Increased HDL-Cholesterol following infusions of acoustic microspheres and apolipoprotein A-I plasmids.
Atherosclerosis
; 241(1): 92-9, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-25969892
ABSTRACT
BACKGROUND:
Low 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.OBJECTIVE:
We 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.METHODS:
Our novel site-specific gene delivery system was examined in naïve rat model and comprised the followingsteps:
(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.RESULTS:
Co-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).CONCLUSIONS:
HDL-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasmídeos
/
Ultrassom
/
Terapia Genética
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Apolipoproteína A-I
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Técnicas de Transferência de Genes
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HDL-Colesterol
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Fígado
/
Microesferas
Tipo de estudo:
Evaluation_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Atherosclerosis
Ano de publicação:
2015
Tipo de documento:
Article