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Aortopathy: a developmental defect with adult pathology? (15.5)
Author(s) -
Riley Ashlie,
Krishnamurthy Varun,
Maddy Kelsey,
Junor Lorain,
Biechler Stefanie,
Hinton Robert,
Goodwin Richard
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.15.5
Subject(s) - elastin , biglycan , aorta , pathology , ascending aorta , neural crest , anatomy , biology , medicine , proteoglycan , microbiology and biotechnology , decorin , cartilage , embryo
Aortopathy is a subclinical disease characterized by aortic dilation, which can result in aortic dissection and/or aortic aneurysm. Hallmarks of aortopathy include vascular smooth muscle cell (VSMC) and elastin fiber misregulation. Elastin hemizygous (Eln+/‐) mice have a thickened and altered arterial wall structure, specifically, aortic root distension and an increase in VSMC layers along the ascending aorta. We hypothesize that aortopathy has a congenital basis with the associated defects originating in the cardiac neural crest (CNC) aorta. Aortic tissues from adult and aged wild type (WT) and Eln+/‐ mice were examined to detect anatomic and/or developmental variation. Sonic Hedgehog (a marker of CNC derived cells), SM22 (a marker of VSMCs), aggrecan and biglycan (proteoglycan markers) were utilized in a novel 3D reconstructive manner to discern spatial and temporal localization. Quantification of these findings revealed that cardiac neural crest‐derived aorta tissue is spatiotemporally associated with VSMC abnormalities, maladaptive matrix remodeling with differential proteoglycan misexpression, and biomechanical dysfunction suggesting a primary role in the development of aortopathy. Grant Funding Source : This study was supported by the AHA 11PRE7210044 (VKK), and the National Institutes of Health HL0851