ArticleJournal of molecular and cellular cardiology2013
Volume overload induces differential spatiotemporal regulation of myocardial soluble guanylyl cyclase in eccentric hypertrophy and heart failure.
Article in Journal of molecular and cellular cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Multiscale model calibrated with a Bayesian algorithm predicts long-term outcomes of treatments for mitral valve regurgitation in animal models.Biomechanics and modeling in mechanobiology · 2026Article
- Contributions of mechanical loading and hormonal changes to eccentric hypertrophy during volume overload: A Bayesian analysis using logic-based network models.PLoS computational biology · 2025Article
- Cardiac Tissue Chips (CTCs) for Modeling Cardiovascular Disease.IEEE transactions on bio-medical engineering · 2019Article
- Loss of smooth muscle CYB5R3 amplifies angiotensin II-induced hypertension by increasing sGC heme oxidation.JCI insight · 2019Article
- Phosphodiesterase 2 inhibition preferentially promotes NO/guanylyl cyclase/cGMP signaling to reverse the development of heart failure.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Mechanotransduction Mechanisms in Mitral Valve Physiology and Disease Pathogenesis.Frontiers in cardiovascular medicine · 2017Review
- Caveolin-3 Overexpression Attenuates Cardiac Hypertrophy via Inhibition of T-type Ca2+ Current Modulated by Protein Kinase Cα in Cardiomyocytes.The Journal of biological chemistry · 2015Article
- Guidelines for translational research in heart failure.Journal of cardiovascular translational research · 2015Article
- Chronic β1-adrenergic blockade enhances myocardial β3-adrenergic coupling with nitric oxide-cGMP signaling in a canine model of chronic volume overload: new insight into mechanisms of cardiac benefit with selective β1-blocker therapy.Basic research in cardiology · 2015Article
- Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: therapeutic perspectives.Pharmacology & therapeutics · 2014Review
- Myofilament dysfunction as an emerging mechanism of volume overload heart failure.Pflugers Archiv : European journal of physiology · 2014Review
- The NO/ONOO-cycle as the central cause of heart failure.International journal of molecular sciences · 2013Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Nitric oxide activation of soluble guanylyl cyclase (sGC) blunts the cardiac stress response, including cardiomyocyte hypertrophy. In the concentric hypertrophied heart, oxidation and re-localization of myocardial sGC diminish cyclase activity, thus aggravating depressed nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling in the pressure-overloaded failing heart. Here, we hypothesized that volume-overload differentially disrupts myocardial sGC activity during early compensated and late decompensated stages of eccentric hypertrophy. To this end, we studied the expression, redox state, subcellular localization, and activity of sGC in the left ventricle of dogs subjected to chordal rupture-induced mitral regurgitation (MR). Unoperated dogs were used as Controls. Animals were studied at 4weeks and 12months post chordal rupture, corresponding with early (4wkMR) and late stages (12moMR) of eccentric hypertrophy. We found that the sGC heterodimer subunits relocalized away from caveolae-enriched lipid raft microdomains at different stages; sGCβ1 at 4wkMR, followed by sGCα1 at 12moMR. Moreover, expression of both sGC subunits fell at 12moMR. Using the heme-dependent NO donor DEA/NO and NO-/heme-independent sGC activator BAY 60-2770, we determined the redox state and inducible activity of sGC in the myocardium, within caveolae and non-lipid raft microdomains. sGC was oxidized in non-lipid raft microdomains at 4wkMR and 12moMR. While overall DEA/NO-responsiveness remained intact in MR hearts, DEA/NO responsiveness of sGC in non-lipid raft microdomains was depressed at 12moMR. Caveolae-localization protected sGC against oxidation. Further studies revealed that these modifications of sGC were also reflected in caveolae-localized cGMP-dependent protein kinase (PKG) and MAPK signaling. In MR hearts, PKG-mediated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) disappeared from caveolae whereas caveolae-localization of phosphorylated ERK5 increased. These findings show that differential oxidation, re-localization, and expression of sGC subunits distinguish eccentric from concentric hypertrophy as well as compensated from decompensated heart failure.
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