What question did this study set out to answer?

To determine the molecular mechanisms regulating myocardial mitochondrial enzymes and assess whether AMPK-α2 controls estrogen-related receptor-α expression during heart failure development.

August 9, 2011HypertensionOpen Access

AMP Activated Protein Kinase-α2 Regulates Expression of Estrogen-Related Receptor-α, a Metabolic Transcription Factor Related to Heart Failure Development

Q: What is the clinical evidence from this study?

Population: Congestive heart failure. Intervention: AMPKα2 manipulation (knockout or overexpression) vs. Basal conditions. Primary outcome: Myocardial ERRα expression.

View Full Paper

Ask AI

Bookmark

Key result

AMPKα2 regulates the expression of myocardial ERRα and its downstream mitochondrial enzymes, with AMPKα2 knockout decreasing ERRα expression in vivo and in vitro.

Key Points

To determine the molecular mechanisms regulating myocardial mitochondrial enzymes and assess whether AMPK-α2 controls estrogen-related receptor-α expression during heart failure development.
Measured ERRα and PGC-1α levels in failing human heart tissue and in mice subjected to chronic pressure overload.
Assessed basal myocardial ERRα and downstream target gene expression in AMPKα2 knockout mice.
Cultured neonatal rat cardiomyocytes to test the effects of constitutively active AMPKα overexpression, AMPKα2 selective gene silencing, and ERRα rescue.
Congestive heart failure in humans and pressure overload in mice induced significant reductions in myocardial ERRα expression, which correlated with left ventricular dysfunction.
AMPKα2 knockout mice exhibited significantly reduced basal levels of myocardial ERRα mRNA, protein, and downstream metabolic targets without altering PGC-1α expression.
Constitutively active AMPKα induced ERRα promoter activity and expression in cardiomyocytes, whereas AMPKα2 silencing repressed ERRα and its targets, an effect partially rescued by ERRα overexpression.

Structured PICO

Population

Human heart failure samples, mice with chronic pressure overload, AMPKα2 knockout mice, and cultured rat neonatal cardiac myocytes

Intervention

Genetic manipulation of AMPKα2 (knockout, silencing, or overexpression of constitutively active AMPKα) and overexpression of ERRα

Comparator

Wild-type controls or basal conditions

Outcome

Expression levels of myocardial estrogen-related receptor-α (ERRα) and its downstream energy metabolism-related genessurrogate

AMPKα2 is a critical regulator of myocardial ERRα expression, a metabolic transcription factor that is significantly decreased in human and murine heart failure.

Authors

XHXinli HuTongji University XXXin XuBeijing Technology and Business University ZLZhongbing LuUniversity of Chinese Academy of Sciences

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

AMPKα2-ERRα axis merits exploration in heart failure models; leaves open therapeutic relevance pending human validation.

Cite This Study

Hu et al. (2011) studied Congestive heart failure. AMPKα2 manipulation (knockout or overexpression) vs. Basal conditions was evaluated on Myocardial ERRα expression. AMPKα2 regulates the expression of myocardial ERRα and its downstream mitochondrial enzymes, with AMPKα2 knockout decreasing ERRα expression in vivo and in vitro.

synapsesocial.com/papers/6a93f6e1c2fc253c55d68bed https://doi.org/10.1161/hypertensionaha.111.174128

Topics

Heart failure HFrEF treatment

View Full Paper

Ask AI

Bookmark

AMP Activated Protein Kinase-α2 Regulates Expression of Estrogen-Related Receptor-α, a Metabolic Transcription Factor Related to Heart Failure Development

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Topics

AMP Activated Protein Kinase-α2 Regulates Expression of Estrogen-Related Receptor-α, a Metabolic Transcription Factor Related to Heart Failure Development

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Topics

Also Consider