Gene silencing therapy for in situ elastic matrix regenerative repair

Sarah Carney, Tom Broekelmann, Robert P. Mecham, Anand Ramamurthi

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

Abstract

Statement of Purpose: Proteolytic disorders, exemplified by abdominal aortic aneurysms (AAAs), aortal expansions are characterized by disruption of elastic fibers by overexpressed matrix metalloproteases (MMPs). These conditions are difficult to reverse since adult cell types are highly deficient in generating elastin precursors and in their ability to regenerate or repair elastic fibers. Treatments are thus mandated to provide both an elastogenic impetus and anti-proteolytic stimuli. Previously, we showed doxycycline (DOX), an MMP inhibitor drug, delivered at low µg/mL doses to provide these dual effects in aneurysmal smooth muscle cell (SMC) by inhibiting the regulatory protein c-Jun-N-terminal kinase (JNK)1. DOX inhibition of the JNK-2 isoform resulted in attenuation of elastolytic MMP-2 and increases in TGF-β1 in a dose-dependent manner; the latter increased elastogenesis & lysyl oxidase (LOX)-mediated crosslinking of elastin. Due to non-specificity of DOX for JNK2, we presently investigated effects of JNK2 gene silencing using anti-JNK2 siRNA complexed with a transfection vector poly-ethylenimine (PEI).

Original languageEnglish
Title of host publicationSociety for Biomaterials Annual Meeting and Exposition 2019
Subtitle of host publicationThe Pinnacle of Biomaterials Innovation and Excellence - Transactions of the 42nd Annual Meeting
PublisherSociety for Biomaterials
Number of pages1
ISBN (Electronic)9781510883901
StatePublished - Jan 1 2019
Event42nd Society for Biomaterials Annual Meeting and Exposition 2019: The Pinnacle of Biomaterials Innovation and Excellence - Seattle, United States
Duration: Apr 3 2019Apr 6 2019

Publication series

NameTransactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium
Volume40
ISSN (Print)1526-7547

Conference

Conference42nd Society for Biomaterials Annual Meeting and Exposition 2019: The Pinnacle of Biomaterials Innovation and Excellence
CountryUnited States
CitySeattle
Period04/3/1904/6/19

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