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J Cardiovasc Transl Res. 2016 Aug;9(4):374-99. doi: 10.1007/s12265-016-9695-z. Epub 2016 May 16.

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

Author information

1
Duke University School of Medicine, Durham, NC, USA. apasipou@duke.edu.
2
Duke/NSF Research Center for Emerging Cardiovascular Technologies, Duke University, Durham, NC, 27710, USA. apasipou@duke.edu.

Abstract

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.

KEYWORDS:

Aortic valvular stenosis; Blood flow; Calcineurin; Cardiomyocyte apoptosis; Concentric LV hypertrophy; Extracellular signal-regulated kinases 1 and 2; Fetal gene reexpression; G protein-coupled receptors; Mitochondrial biogenesis; Mitogen-activated protein kinases; Myocardial fibrosis; Myocardial hypertrophic and hyperplastic growth; PI3K(p110α) lipid kinase–Akt serine/threonine kinase pathway; Pathological cardiac hypertrophy and failure; Physiological cardiac hypertrophy; Pressure overload; Receptor tyrosine kinases; Replication of cardiomyocyte sarcomeres in-parallel and in-series; Resident endogenous stem/progenitor cells and myocardial regeneration; Subendocardial ischemia; Transvalvular gradient

PMID:
27184804
PMCID:
PMC4992466
DOI:
10.1007/s12265-016-9695-z
[Indexed for MEDLINE]
Free PMC Article

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