Synapse
⌘+K
Synapse
PulseExploreClubsResearchersJournals
Instagram
HomeClubsExplore
August 21, 2007Proceedings of the National Academy of SciencesOpen Access

Genetic inhibition of cardiac ERK1/2 promotes stress-induced apoptosis and heart failure but has no effect on hypertrophy in vivo

View Full Paper
Ask AI
Bookmark
Share

Why the study?

Does genetic inhibition of cardiac ERK1/2 prevent cardiac hypertrophy or promote heart failure in response to stress in mice?

Population

Erk1 and Erk2 mice, and transgenic mice with inducible expression of an ERK1/2-inactivating phosphatase in…

Design

Preclinical

Authors

NPNicole H. PurcellUniversity of Southern CaliforniaBWBenjamin J. WilkinsChildren's Hospital of PhiladelphiaAYAllen J. YorkHoward Hughes Medical Institute

Discussion

Loading...

Member takes

Implication

Questions ERK1/2 requirement for hypertrophy; leaves open its protective role against decompensation in pressure overload.

Key Points

  • This research aims to understand the role of ERK1/2 signaling in cardiac hypertrophy and heart failure.
  • Utilized Erk1(-/-) and Erk2(+/-) mice models to assess cardiac response to various stimuli.
  • Inducible expression of dual-specificity phosphatase 6 was performed to inhibit ERK1/2 in the heart.
  • Monitored cardiac growth and myocyte apoptosis under different physiological and pathological stress conditions.
  • Inhibition of ERK1/2 did not affect hypertrophic response to pressure overload, neuroendocrine agonist, or exercise.
  • Cardiac failure occurred after pressure overload in models lacking ERK1/2, coupled with increased apoptosis (myocyte TUNEL positive).
  • Findings suggest ERK1/2 has a protective role against heart failure but not in hypertrophy.

Structured PICO

Does genetic inhibition of cardiac ERK1/2 prevent cardiac hypertrophy or promote heart failure in response to stress in mice?

P
Population
Erk1(-/-) and Erk2(+/-) mice, and transgenic mice with inducible expression of an ERK1/2-inactivating phosphatase (dual-specificity phosphatase 6) in the heart
I
Intervention
Genetic inhibition of cardiac ERK1/2 signaling (via knockout or inducible phosphatase expression) subjected to pressure overload stimulation, neuroendocrine agonist infusion, or exercise
O
Outcome
Cardiac hypertrophic growth response to pressure overload stimulation, neuroendocrine agonist infusion, or exercisesurrogate

ERK1/2 signaling is not required for mediating physiologic or pathologic cardiac hypertrophy in vivo, but it plays a critical protective role against apoptosis and heart failure in response to pathologic stimuli.

Cite This Study

Purcell et al. (2007) studied this question.

synapsesocial.com/papers/6a1be8fbfc87fd06169cea74https://doi.org/10.1073/pnas.0610906104

Topics

Heart failureHFrEF treatment
View Full Paper
Ask AI
Bookmark
Share

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Defective Thymocyte Maturation in p44 MAP Kinase (Erk 1) Knockout Mice1999 · 653 citations
  2. 2Mechanistic Basis for Catalytic Activation of Mitogen-activated Protein Kinase Phosphatase 3 by Extracellular Signal-regulated Kinase2000 · 90 citations
  3. 3Physical Training, Vegetative Regulation, and Cardiac Hypertrophy1987 · 25 citations
  4. 4Cardiac and skeletal muscle adaptations to voluntary wheel running in the mouse2001 · 380 citations
  5. 5Targeted inhibition of calcineurin prevents agonist-induced cardiomyocyte hypertrophy2000 · 297 citations