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Current strategies to prevent restenosis following endovascular treatment include the local delivery of anti-proliferative agents to inhibit vascular smooth muscle cell (VSMC) proliferation and migration. These agents, not specific to VSMCs, are deposited on the luminal surface and therefore target endothelial cells and delay vascular healing. Cell-targeted therapies, (e.g., RNA aptamers), can potentially overcome these safety concerns by specifically binding to VSMC and inhibiting proliferation and migration. The purpose of this study was to therefore demonstrate the ability of a perfusion catheter to deliver cell-specific RNA aptamer inhibitors directly to the vessel wall. RNA aptamers specific to VSMCs were developed using an in vitro cell-based systematic evolution of ligand by exponential enrichment selection process. Two aptamers (Apt01 and Apt14) were evaluated ex vivo using harvested pig arteries in a pulsatile flow bioreactor. Local drug delivery of the aptamers into the medial wall was accomplished using a novel perfusion catheter. We demonstrated the feasibility to deliver aptamer-based drugs directly to the medial layer of an artery using a perfusion catheter. Such cell-specific targeted therapeutic drugs provide a potentially safer and more effective treatment option for patients with vascular disease.
This article was published in the following journal.
Name: Molecular therapy. Nucleic acids
Aptamers are versatile nucleic acid-based macromolecules characterized by their high affinity and specificity to a specific target. Taking advantage of such binding properties, several aptamers have b...
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Thickening and loss of elasticity of the walls of medium and large muscular ARTERIES with lesions in the innermost layer of the artery (ARTERIAL INTIMA). This disease process of atherogenesis includes the retention of cholesterol-rich LIPOPROTEINS and their binding to PROTEOGLYCANS in the arterial intima, generation of proinflammatory molecules that recruit MACROPHAGES to the subendothelial space, formation of FOAM CELLS, and eventual calcification of the arterial wall. These arterial plaques (atheromas) contain CARBOHYDRATES; BLOOD; and CALCIUM.
MYOCARDIAL INFARCTION in which the anterior wall of the heart is involved. Anterior wall myocardial infarction is often caused by occlusion of the left anterior descending coronary artery. It can be categorized as anteroseptal or anterolateral wall myocardial infarction.
A method of generating a large library of randomized nucleotides and selecting NUCLEOTIDE APTAMERS by iterative rounds of in vitro selection. A modified procedure substitutes AMINO ACIDS in place of NUCLEOTIDES to make PEPTIDE APTAMERS.
The outermost layer of a cell in most PLANTS; BACTERIA; FUNGI; and ALGAE. The cell wall is usually a rigid structure that lies external to the CELL MEMBRANE, and provides a protective barrier against physical or chemical agents.
Delivery of drugs into an artery.
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