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Calcific Aortic Valve Disease: Part 2-Morphomechanical Abnormalities, Gene Reexpression, and Gender Effects on Ventricular Hypertrophy and Its Reversibility.

Publication ,  Journal Article
Pasipoularides, A
Published in: J Cardiovasc Transl Res
August 2016

In part 1, we considered cytomolecular mechanisms underlying calcific aortic valve disease (CAVD), hemodynamics, and adaptive feedbacks controlling pathological left ventricular hypertrophy provoked by ensuing aortic valvular stenosis (AVS). In part 2, we survey diverse signal transduction pathways that precede cellular/molecular mechanisms controlling hypertrophic gene expression by activation of specific transcription factors that induce sarcomere replication in-parallel. Such signaling pathways represent potential targets for therapeutic intervention and prevention of decompensation/failure. Hypertrophy provoking signals, in the form of dynamic stresses and ligand/effector molecules that bind to specific receptors to initiate the hypertrophy, are transcribed across the sarcolemma by several second messengers. They comprise intricate feedback mechanisms involving gene network cascades, specific signaling molecules encompassing G protein-coupled receptors and mechanotransducers, and myocardial stresses. Future multidisciplinary studies will characterize the adaptive/maladaptive nature of the AVS-induced hypertrophy, its gender- and individual patient-dependent peculiarities, and its response to surgical/medical interventions. They will herald more effective, precision medicine treatments.

Duke Scholars

Published In

J Cardiovasc Transl Res

DOI

EISSN

1937-5395

Publication Date

August 2016

Volume

9

Issue

4

Start / End Page

374 / 399

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function, Left
  • Stem Cells
  • Signal Transduction
  • Sex Factors
  • Risk Factors
  • Prognosis
  • Mitochondria, Heart
  • Male
  • Hypertrophy, Left Ventricular
 

Citation

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ICMJE
MLA
NLM
Journal cover image

Published In

J Cardiovasc Transl Res

DOI

EISSN

1937-5395

Publication Date

August 2016

Volume

9

Issue

4

Start / End Page

374 / 399

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function, Left
  • Stem Cells
  • Signal Transduction
  • Sex Factors
  • Risk Factors
  • Prognosis
  • Mitochondria, Heart
  • Male
  • Hypertrophy, Left Ventricular