عنوان

Ultrasound-targeted microRNA-26a Therapy for Abdominal Aortic Aneurysms

Number

TLpq2323545305

.Language of Text, Soundtrack etc

انگلیسی

Title Proper

Ultrasound-targeted microRNA-26a Therapy for Abdominal Aortic Aneurysms

General Material Designation

[Thesis]

First Statement of Responsibility

Elfaki, Lina Abdellatif

Subsequent Statement of Responsibility

Leong-Poi, Howard

Name of Publisher, Distributor, etc.

University of Toronto (Canada)

Date of Publication, Distribution, etc.

2019

Specific Material Designation and Extent of Item

151

Dissertation or thesis details and type of degree

M.Sc.

Body granting the degree

University of Toronto (Canada)

Text preceding or following the note

2019

Text of Note

Abdominal aortic aneurysms (AAA) affect ~5% of adults and are characterized by vessel inflammation, aortic smooth muscle cell (haSMC) depletion and extracellular matrix (ECM) degradation. microRNA-26a (miR-26a) regulates haSMC function but is reduced in human AAA. We induced targeted delivery of miR-26a or scrambled-control miR to the infrarenal aorta of a clinically relevant rat AAA model using ultrasound-targeted microbubble destruction (UTMD). An additional control group received no therapy. In-vitro, haSMCs were stimulated with the inflammatory interleukin-1β (IL-1β; 20ng/ml) and transfected with miR-26a, antimiR-26a and scrambled-control miR. In-vivo, UTMD of miR-26a downregulated inflammatory cytokines (IL-1β, IL-6 and TGF-β) and elastolytic enzymes (MMP-2 and MMP-9), leading to reduced ECM degradation and AAA dilation. In-vitro, miR-26a downregulated TGF-β signaling (SMAD1 and SMAD4) and differentiation markers (ACTA2 and TAGLN) but enhanced haSMC proliferation, which alludes to a phenotypic switch towards greater haSMC survival. Thus, this study demonstrates a promising miRNA-based UTMD therapy for AAA.

Genetics

Medicine

Elfaki, Lina Abdellatif

Leong-Poi, Howard

Electronic name

p

[Thesis]

276903

a

Y