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Clinical-pathological correlations of BAV and the attendant thoracic aortopathies. Part 2: Pluridisciplinary perspective on their genetic and molecular origins.

Publication ,  Journal Article
Pasipoularides, A
Published in: J Mol Cell Cardiol
August 2019

Bicuspid aortic valve (BAV) arises during valvulogenesis when 2 leaflets/cusps of the aortic valve (AOV) are fused together. Its clinical manifestations pertain to faulty AOV function, the associated aortopathy, and other complications surveyed in Part 1 of the present bipartite-series. Part 2 examines mainly genetic and epigenetic causes of BAV and BAV-associated aortopathies (BAVAs) and disease syndromes (BAVD). Part 1 explored the heterogeneity among subsets of patients with BAV and BAVA/BAVD, and investigated abnormal fluid dynamic stress and strain patterns sustained by the cusps. Specific BAV morphologies engender systolic outflow asymmetries, associated with abnormal aortic regional wall-shear-stress distributions and the expression/localization of BAVAs. Understanding fluid dynamic factors besides the developmental mechanisms and underlying genetics governing these congenital anomalies is necessary to explain patient predisposition to aortopathy and phenotypic heterogeneity. BAV aortopathy entails complex/multifactorial pathophysiology, involving alterations in genetics, epigenetics, hemodynamics, and in cellular and molecular pathways. There is always an interdependence between organismic developmental signals and genes-no systemic signals, no gene-expression; no active gene, no next step. An apposite signal induces the expression of the next developmental gene, which needs be expressed to trigger the next signal, and so on. Hence, embryonic, then post-partum, AOV and thoracic aortic development comprise cascades of developmental genes and their regulation. Interdependencies between them arise, entailing reciprocal/cyclical mutual interactions and adaptive feedback loops, by which developmental morphogenetic processes self-correct responding to environmental inputs/reactions. This Survey can serve as a reference point and driver for further pluridisciplinary BAV/BAVD studies and their clinical translation.

Duke Scholars

Published In

J Mol Cell Cardiol

DOI

EISSN

1095-8584

Publication Date

August 2019

Volume

133

Start / End Page

233 / 246

Location

England

Related Subject Headings

  • Transcriptome
  • Phenotype
  • Mice
  • Inheritance Patterns
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Heart Valve Diseases
  • Genotype
  • Epigenesis, Genetic
  • Cardiovascular System & Hematology
 
Journal cover image

Published In

J Mol Cell Cardiol

DOI

EISSN

1095-8584

Publication Date

August 2019

Volume

133

Start / End Page

233 / 246

Location

England

Related Subject Headings

  • Transcriptome
  • Phenotype
  • Mice
  • Inheritance Patterns
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Heart Valve Diseases
  • Genotype
  • Epigenesis, Genetic
  • Cardiovascular System & Hematology