title: Asymmetric cell-matrix and biomechanical abnormalities in elastin insufficiency induced aortopathy.
abstract: Aortopathy is characterized by vascular smooth muscle cell (VSMC) abnormalities and elastic fiber fragmentation. Elastin insufficient (Eln (+/-)) mice demonstrate latent aortopathy similar to human disease. We hypothesized that aortopathy manifests primarily in the aorto-pulmonary septal (APS) side of the thoracic aorta due to asymmetric cardiac neural crest (CNC) distribution. Anatomic (aortic root vs. ascending aorta) and molecular (APS vs. non-APS) regions of proximal aorta tissue were examined in adult and aged wild type (WT) and mutant (Eln (+/-)) mice. CNC, VSMCs, elastic fiber architecture, proteoglycan expression, morphometrics and biomechanical properties were examined using histology, 3D reconstruction, micropipette aspiration and in vivo magnetic resonance imaging (MRI). In the APS side of Eln (+/-) aorta, Sonic Hedgehog (SHH) is decreased while SM22 is increased. Elastic fiber architecture abnormalities are present in the Eln (+/-) aortic root and APS ascending aorta, and biglycan is increased in the aortic root while aggrecan is increased in the APS aorta. The Eln (+/-) ascending aorta is stiffer than the aortic root, the APS side is thicker and stiffer than the non-APS side, and significant differences in the individual aortic root sinuses are observed. Asymmetric structure-function abnormalities implicate regional CNC dysregulation in the development and progression of aortopathy.
authors.affiliation: Division of Cardiology, the Heart Institute, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, MLC 7020, Cincinnati, OH, 45229, USA.
authors.forename: Varun K
authors.initials: VK
authors.lastname: Krishnamurthy
authors.forename: Ashlie N
authors.initials: AN
authors.lastname: Evans
authors.forename: Janaka P
authors.initials: JP
authors.lastname: Wansapura
authors.forename: Hanna
authors.initials: H
authors.lastname: Osinska
authors.forename: Kelsey E
authors.initials: KE
authors.lastname: Maddy
authors.forename: Stefanie V
authors.initials: SV
authors.lastname: Biechler
authors.forename: Daria A
authors.initials: DA
authors.lastname: Narmoneva
authors.forename: Richard L
authors.initials: RL
authors.lastname: Goodwin
authors.forename: Robert B
authors.initials: RB
authors.lastname: Hinton
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000002:abnormalities* / Q000502:physiology*; D001018:Aortic Diseases / Q000473:pathology / Q000503:physiopathology; D001696:Biomechanical Phenomena; D002648:Child; D055119:Elastic Modulus; D004549:Elastin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008822:Mice, Transgenic; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D009432:Neural Crest / Q000002:abnormalities; D011509:Proteoglycans / Q000378:metabolism
chemical_list: D011509:Proteoglycans; D004549:Elastin