What question did this study set out to answer?

To evaluate myocardial oxidative capacity and elucidate the hormonal factors driving mitochondrial transcriptional downregulation in chronic heart failure.

May 9, 2009Circulation Heart FailureOpen Access

Control by Circulating Factors of Mitochondrial Function and Transcription Cascade in Heart Failure

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Why the study?

Does angiotensin-converting enzyme inhibition or exposure to circulating factors alter cardiac oxidative capacity and mitochondrial transcription cascade in heart failure models?

Population

Patients with chronic heart failure treated with angiotensin-converting enzyme inhibition, a rat model of…

Comparison

Angiotensin-converting enzyme inhibition… vs Nonfailing controls; untreated/control conditions

Design

Preclinical

Follow-up

48 hours (for cultured myocytes)

Authors

AGAnne GarnierUniversité Paris-Sud JZJoffrey ZollUniversité de Strasbourg DFDominique FortinUniversité Paris-Sud

Discussion

Member takes

Implication

ACEi may incompletely restore mitochondrial function in HF; leaves open PGC-1α modulation as a therapeutic target.

Key Points

To evaluate myocardial oxidative capacity and elucidate the hormonal factors driving mitochondrial transcriptional downregulation in chronic heart failure.
Assessed cardiac oxidative capacity and PGC-1α protein expression in saponin-permeabilized myocardial fibers from ACE-inhibitor-treated heart failure patients versus nonfailing controls.
Evaluated cardiac mitochondrial function and transcription cascade recovery in a rat model of myocardial infarction treated with ACE inhibitors.
Exposed cultured adult rat ventricular myocytes for 48 hours to endothelin-1, angiotensin II, aldosterone, phenylephrine, or isoprenaline to quantify changes in PGC-1α mRNA expression.
Patients with chronic heart failure treated with ACE inhibitors showed 25% lower cardiac oxidative capacity and 34% lower PGC-1α protein content compared with nonfailing controls.
ACE inhibitor therapy provided only partial protection of cardiac mitochondrial function and the transcription cascade in the post-infarction rat model.
In cultured myocytes, endothelin-1 and angiotensin II reduced PGC-1α mRNA by 30% and 20%, respectively, whereas aldosterone and isoprenaline increased its expression.

Structured PICO

Does angiotensin-converting enzyme inhibition or exposure to circulating factors alter cardiac oxidative capacity and mitochondrial transcription cascade in heart failure models?

Population

Patients with chronic heart failure treated with angiotensin-converting enzyme inhibition, a rat model of myocardial infarction, and cultured adult rat ventricular myocytes

Intervention

Angiotensin-converting enzyme inhibition (in vivo); 48-hour exposure to endothelin-1, angiotensin II, aldosterone, phenylephrine, or isoprenaline (in vitro)

Comparator

Nonfailing controls (human); untreated/control conditions (experimental models)

Outcome

Cardiac oxidative capacity and proliferator-activated receptor-γ coactivator-1α protein/mRNA contentsurrogate

Despite ACE inhibitor therapy, cardiac oxidative capacity remains reduced in heart failure, potentially driven by endothelin-1 and angiotensin II downregulating the mitochondrial transcription cascade.

Cite This Study

Garnier et al. (2009) studied this question.

synapsesocial.com/papers/6a100751b6f5ee0401603535 https://doi.org/10.1161/circheartfailure.108.812099

Topics

Heart failure HFrEF treatment

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Control by Circulating Factors of Mitochondrial Function and Transcription Cascade in Heart Failure

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Control by Circulating Factors of Mitochondrial Function and Transcription Cascade in Heart Failure

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

Also Consider