In Vivo Human MCP-1 Transfection in Porcine Arteries by Intravascular Electroporation

Seidler, Randolph; Allgäuer, Susanne; Ailinger, Susanne; Sterner, Andreas; Dev, Nagendu B.; Rabussay, Dietmar; Doods, Henri; Lenter, Martin

doi:10.1007/s11095-005-6334-9

Cited by 9 publications

(2 citation statements)

References 27 publications

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“…A micro-infusion Bullfrog catheter [ 21 ] (Mercator Medsystems, San Leandro, CA, USA) was used to deliver the cDNA into the coronary artery wall and a custom made intravascular electroporation catheter [ 45 ] (Cardigant Medical Inc., Manhattan Beach, CA, USA) to transiently electropermeabilize SMCs, allowing their loading with cDNA. Since both catheters were designed for 3 mm arteries, before performing an in vivo gene delivery procedure, a coronary artery segment of 3 mm diameter was identified using IVUS.…”

Section: Methodsmentioning

confidence: 99%

Long-term spironolactone treatment reduces coronary TRPC expression, vasoconstriction, and atherosclerosis in metabolic syndrome pigs

Chen

Riley

et al. 2017

Basic Res Cardiol

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Coronary transient receptor potential canonical (TRPC) channel expression is elevated in metabolic syndrome (MetS). However, differential contribution of TRPCs to coronary pathology in MetS is not fully elucidated. We investigated the roles of TRPC1 and TRPC6 isoforms in coronary arteries of MetS pigs and determined whether long-term treatment with a mineralocorticoid receptor inhibitor, spironolactone, attenuates coronary TRPC expression and associated dysfunctions. MetS coronary arteries exhibited significant atherosclerosis, endothelial dysfunction, and increased histamine-induced contractions. Immunohistochemical studies revealed that TRPC6 immunostaining was significantly greater in the medial layer of MetS pig coronary arteries compared to that in Lean pigs, whereas little TRPC6 immunostaining was found in atheromas. Conversely, TRPC1 immunostaining was weak in the medial layer but strong in MetS atheromas, where it was predominantly localized to macrophages. Spironolactone treatment significantly decreased coronary TRPC expression and dysfunctions in MetS pigs. In vivo targeted delivery of the dominant-negative (DN)-TRPC6 cDNA to the coronary wall reduced histamine-induced calcium transients in the MetS coronary artery medial layer, implying a role for TRPC6 in mediating calcium influx in MetS coronary smooth muscles. Monocyte adhesion was increased in Lean pig coronary arteries cultured in the presence of aldosterone; and spironolactone antagonized this effect, suggesting that coronary mineralocorticoid receptor activation may regulate macrophage infiltration. TRPC1 expression in atheroma macrophages was associated with advanced atherosclerosis, whereas medial TRPC6 upregulation correlated with increased histamine-induced calcium transients and coronary contractility. We propose that long-term spironolactone treatment may be a therapeutic strategy to decrease TRPC expression and coronary pathology associated with MetS.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-017-0643-0) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Long-term spironolactone treatment reduces coronary TRPC expression, vasoconstriction, and atherosclerosis in metabolic syndrome pigs

Chen

Riley

et al. 2017

Basic Res Cardiol

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“…However, the clinical applications of gene therapy have been limited by the low efficiency of gene vectors and in some particular cases with technical hurdles associated with local gene delivery 5. The use of “naked” DNA (i.e., DNA without gene vector) usually results in low transfection efficiency,6 which can be improved by electroporation,7 ultrasound‐, or hydrodynamics‐based techniques 8. Alternatively, a long list of nonviral and viral gene vectors have been investigated to improve transfection efficiency in tissues.…”

Section: Introductionmentioning

confidence: 99%

Cationized pullulan 3D matrices as new materials for gene transfer

Juan

Hlawaty

Chaubet

et al. 2007

J Biomedical Materials Res

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This study deals with the development of a novel biocompatible cationized pullulan three-dimensional matrix for gene delivery. A water-soluble cationic polysaccharide, diethylaminoethyl-pullulan (DEAE-pullulan), was first synthesized and characterized. Fluorescence quenching and gel retardation assays evidenced the complexation in solution of DNA with DEAE-pullulan, but not with neutral pullulan. On cultured smooth muscle cells (SMCs) incubated with DEAE-pullulan and a plasmid vector expressing a secreted form of alkaline phosphatase (pSEAP), SEAP activity was 150-fold higher than with pSEAP alone or pSEAP with neutral pullulan. DEAE-pullulan was then chemically crosslinked using phosphorus oxychloride. The resulting matrices were obtained in less than a minute and molded as discs of 12 mm diameter and 2 mm thickness. Such DEAE-pullulan 3D matrices were loaded with up to 50 microg of plasmid DNA, with a homogeneous plasmid loading observed with YOYO-1 fluorescence staining. Moreover, the DEAE-pullulan matrix was shown to protect pSEAP from DNase I degradation. Incubation of cultured SMCs with pSEAP-loaded DEAE-pullulan matrices resulted in significant gene transfer without cell toxicity. This study suggests that these cationized pullulan 3D matrices could be useful biomaterials for local gene transfer.

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Applicator and Electrode Design for In Vivo DNA Delivery by Electroporation

Rabussay

2008

Methods in Molecular Biology

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As in vivo electroporation advances from the preclinical phase to clinical studies and eventually to routine medical practice, the design of electroporation devices becomes increasingly important. Achieving safety and efficacy levels that meet regulatory requirements, as well as user and patient friendliness, are major design considerations. In addition, the devices will have to be economical to manufacture. This chapter will focus on the design of applicators and electrodes, the pieces of hardware in direct contact with the user and the patient, and thus key elements responsible for the safety and efficacy of the procedure. The two major foreseeable applications of the technology in the DNA field are for gene therapy and DNA vaccination. Design requirements differ considerably for these applications and for the diseases to be treated or prevented. In addition to the trend of device differentiation, there is also a trend to build devices capable of performing both the step of delivering the DNA to the target tissue and the subsequent step of electroporation. This chapter presents the electrical and biological principles underlying applicator and electrode design, gives an overview of existing devices, and discusses their advantages and disadvantages. The chapter also outlines major design considerations, including regulatory pathways, and points out potential future developments.

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In Vivo Human MCP-1 Transfection in Porcine Arteries by Intravascular Electroporation

Abstract: The present study demonstrates that transluminal catheter-based electroporation provides an efficient technology for nonviral intravascular gene transfer by just applying unformulated DNA.

Cited by 9 publications

References 27 publications

Long-term spironolactone treatment reduces coronary TRPC expression, vasoconstriction, and atherosclerosis in metabolic syndrome pigs

Long-term spironolactone treatment reduces coronary TRPC expression, vasoconstriction, and atherosclerosis in metabolic syndrome pigs

Cationized pullulan 3D matrices as new materials for gene transfer

Applicator and Electrode Design for In Vivo DNA Delivery by Electroporation

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