Asymmetric cell-matrix and biomechanical abnormalities in elastin insufficiency induced aortopathy

Area of Science:

• Cardiovascular Biology
• Developmental Biology
• Biomedical Engineering

Background:

• Aortopathy involves vascular smooth muscle cell (VSMC) dysfunction and elastic fiber damage.
• Elastin insufficient (Eln (+/-)) mice model latent human aortopathy.
• Asymmetric cardiac neural crest (CNC) distribution may drive aortopathy in the aorto-pulmonary septal (APS) region.

Purpose of the Study:

• To investigate the hypothesis that aortopathy manifests asymmetrically in the thoracic aorta, specifically on the APS side.
• To examine regional differences in aortic structure and function in wild type (WT) and Eln (+/-) mice.

Main Methods:

• Histology, 3D reconstruction, and micropipette aspiration were used to analyze aortic tissue.
• In vivo magnetic resonance imaging (MRI) assessed biomechanical properties.
• Examined CNC, VSMCs, elastic fibers, proteoglycans, morphometrics, and biomechanics in adult and aged WT and Eln (+/-) mice.

Main Results:

• Eln (+/-) aortas showed decreased Sonic Hedgehog (SHH) and increased SM22 on the APS side.
• Elastic fiber abnormalities and increased biglycan/aggrecan were observed in specific aortic regions.
• The Eln (+/-) ascending aorta was stiffer and thicker on the APS side compared to the non-APS side and aortic root.

Conclusions:

• Asymmetric structural and functional abnormalities in the Eln (+/-) aorta suggest regional CNC dysregulation.
• This regional dysregulation is implicated in the development and progression of aortopathy.
• Findings highlight the importance of asymmetric aortic development in disease pathogenesis.