Selective microRNA suppression in human thoracic aneurysms: relationship of miR-29a to aortic size and proteolytic induction.
BACKGROUND
Increasing evidence points to a direct role for altered microRNA (miRNA or miR) expression levels in cardiovascular remodeling and disease progression. Although alterations in miR expression levels have been directly linked to cardiac hypertrophy, fibrosis, and remodeling, their role in regulating gene expression during thoracic aortic aneurysm (TAA) development has yet to be explored.


RESULTS
The present study examined miR expression levels in aortic tissue specimens collected from patients with ascending TAAs by quantitative real-time PCR, and observed decreased miR expression (miRs -1, -21, -29a, -133a, and -486) as compared with normal aortic specimens. A significant relationship between miR expression levels (miRs -1, -21, -29a, and -133a) and aortic diameter was identified; as aortic diameter increased, miR expression decreased. Through the use of a bioinformatics approach, members of the matrix metalloproteinase (MMP) family, proteins involved in TAA development, were examined for putative miR binding sites. MMP-2 and MMP-9 were identified as potential targets for miR-29a and miR-133a, respectively, and MMP-2 was subsequently verified as a miR-29a target in vitro. A significant inverse relationship between miR-29a and total MMP-2 was then identified in the clinical TAA specimens.


CONCLUSIONS
These findings demonstrate altered miR expression patterns in clinical TAA specimens, suggesting that the loss of specific miR expression may allow for the elaboration of specific MMPs capable of driving aortic remodeling during TAA development. Importantly, these data suggest that these miRs have biological and clinical relevance to the behavior of TAAs and may provide significant targets for therapeutic and diagnostic applications.
Cardiothoracic Surgery Research, Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
Jeffrey A
JA
Jones
Robert E
RE
Stroud
Elizabeth C
EC
O'Quinn
Laurel E
LE
Black
Jeremy L
JL
Barth
John A
JA
Elefteriades
Joseph E
JE
Bavaria
Joseph H
JH
Gorman
Robert C
RC
Gorman
Francis G
FG
Spinale
John S
JS
Ikonomidis
D000368:Aged; D001013:Aorta, Thoracic / Q000254:growth & development / Q000378:metabolism*; D017545:Aortic Aneurysm, Thoracic / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009929:Organ Size
C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9