What question did this study set out to answer?

To determine whether nitric oxide is causally involved in TGFβ-induced apoptosis in cardiac myocytes during the progression to heart failure.

December 29, 2010Journal of Cellular Physiology

TGFβ receptor activation enhances cardiac apoptosis via SMAD activation and concomitant NO release

Q: What is the clinical evidence from this study?

Study design: Other. Population: Heart failure. Intervention: Transforming growth factor β (TGFβ) stimulation vs. Unstimulated cells or cells treated with NOS/TGFβ inhibitors. Primary outcome: Apoptosis and NO release.

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Key result

In cardiomyocytes, TGFβ-induced apoptosis is mediated via TGFβ receptor activation that concomitantly activates SMAD transcription factors and the eNOS/NO/sGC pathway.

Population

Isolated ventricular cardiomyocytes of adult rats and eNOS KO mice

Comparison

TGFβ stimulation with or without NOS inhibitors… vs Control/unstimulated cardiomyocytes

Design

Preclinical

Authors

JHJacqueline HegerJustus-Liebig-Universität Gießen BWBjörn WargaJustus-Liebig-Universität Gießen BMBettina MeyeringJustus-Liebig-Universität Gießen

Discussion

Member takes

Implication

May inform TGFβ-driven cardiomyocyte loss in heart failure; leaves open clinical relevance pending human validation.

Key Points

To determine whether nitric oxide is causally involved in TGFβ-induced apoptosis in cardiac myocytes during the progression to heart failure.
Treated isolated adult rat ventricular cardiomyocytes and cardiomyocytes from eNOS knockout mice with TGFβ1 alongside isoform-selective nitric oxide synthase (NOS) inhibitors, a soluble guanylyl cyclase inhibitor (ODQ), or a TGFβ receptor antagonist.
Assessed cardiomyocyte apoptosis, nitric oxide production, eNOS phosphorylation at serine 1177, SMAD binding activity, SMAD2 phosphorylation, and SMAD7 expression.
TGFβ1 stimulated nitric oxide release and apoptosis via eNOS phosphorylation at serine 1177; both effects were inhibited by the pan-NOS inhibitor ETU and the soluble guanylyl cyclase inhibitor ODQ, but not by iNOS or nNOS inhibitors, and NO release failed to occur in eNOS knockout mice.
TGFβ receptor blockade completely abrogated SMAD2 phosphorylation, SMAD binding activity, SMAD7 expression, nitric oxide formation, and apoptosis, whereas NOS inhibition selectively prevented apoptosis and nitric oxide release without altering SMAD pathway activation.

Structured PICO

Population

Isolated ventricular cardiomyocytes from adult rats and eNOS knockout mice used to study heart failure progression mechanisms.

Intervention

TGFβ(1) stimulation with or without NOS inhibitors (ETU, 1400 W, TFA), sGC inhibitor (ODQ), or TGFβ receptor antagonist

Comparator

Control/unstimulated cardiomyocytes

Outcome

Apoptosis, NO release, and SMAD activationsurrogate

TGFβ induces cardiomyocyte apoptosis via simultaneous activation of SMAD transcription factors and the eNOS/NO/sGC pathway, highlighting a potential mechanism for heart failure progression.

Cite This Study

Heger et al. (2010) studied Heart failure. Transforming growth factor β (TGFβ) stimulation vs. Unstimulated cells or cells treated with NOS/TGFβ inhibitors was evaluated on Apoptosis and NO release. In cardiomyocytes, TGFβ-induced apoptosis is mediated via TGFβ receptor activation that concomitantly activates SMAD transcription factors and the eNOS/NO/sGC pathway.

synapsesocial.com/papers/6a91600cb68aa5977865e7cf https://doi.org/10.1002/jcp.22619

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TGFβ receptor activation enhances cardiac apoptosis via SMAD activation and concomitant NO release

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

TGFβ receptor activation enhances cardiac apoptosis via SMAD activation and concomitant NO release

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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