Evidence map›Paper›PMID 25969892›Full record

ArticleAtherosclerosis2015

Therapeutic ultrasound: Increased HDL-Cholesterol following infusions of acoustic microspheres and apolipoprotein A-I plasmids.

Jason W Castle, Kevin P Kent, Ying Fan, Kirk D Wallace, Cynthia E L Davis, Jeannette C Roberts, Michael E Marino, Kai E Thomenius, Hae W Lim, Eric Coles and 3 more

Abstract readEvaluation Study
In one paragraph

Article in Atherosclerosis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.3field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 12 citations in OpenAlex.

  1. Sonoporation for Augmenting Chemotherapy of Pancreatic Ductal Adenocarcinoma.Methods in molecular biology (Clifton, N.J.) · 2020
    Trial
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Jason W CastleGeneral Electric Global Research, Niskayuna, NY, USA. Electronic address: castle@ge.com.
Kevin P KentFormerly GE Global Research, Niskayuna, NY, USA.
Ying FanGeneral Electric Global Research, Niskayuna, NY, USA.
Kirk D WallaceGeneral Electric Global Research, Niskayuna, NY, USA.
Cynthia E L DavisGeneral Electric Global Research, Niskayuna, NY, USA.
Jeannette C RobertsGeneral Electric Global Research, Niskayuna, NY, USA.
Michael E MarinoGeneral Electric Global Research, Niskayuna, NY, USA.
Kai E ThomeniusGeneral Electric Global Research, Niskayuna, NY, USA.
Hae W LimFormerly GE Global Research, Niskayuna, NY, USA.
Eric ColesSonoGene LLC, Glen Ellyn, IL, USA.
Michael H DavidsonSonoGene LLC, Glen Ellyn, IL, USA; University of Chicago, Pritzker School of Medicine, Chicago, IL, USA.
Steven B FeinsteinSonoGene LLC, Glen Ellyn, IL, USA; Rush University Medical Center, Chicago, IL, USA.
Anthony DeMariaSulpizio Cardiovascular Center, University of California, San Diego, CA, USA.
General Electric (United States) · USGlen Ellyn Public Library · USGE Global Research (United States) · USUniversity of California, San Diego · US

Funding

Development of novel tissue directed ultra sound therapeutic gene delivery systemR44HL095238 · NHLBI · SONOGENE, LLC · PI COLES, ERIC · 2009 to 2011
$813k
NHLBI NIH HHS R44 HL095238
6 · The paper itself

Abstract

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.

Indexed as

Gene Transfer TechniquesMicrospheresPlasmidsAnimalsApolipoprotein A-IBiomarkersCholesterol, HDLFeasibility StudiesGenetic TherapyHumansInjections, IntravenousLiverMaleModels, AnimalRats, Sprague-DawleyRNA, MessengerAPOA1 protein, humanApolipoprotein A-IBiomarkersCholesterol, HDLRNA, MessengerAcoustic microspheresApoA-IDrug deliveryHDL-CHypo-alphalipoproteinemiaOptison™Ultrasound

Identifiers

PMID25969892
PMCPMC4466163
OpenAlexW1758138970

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.