What question did this study set out to answer?

The study investigates the role of necrosis in cardiac myocyte loss as a contributor to heart failure.

August 10, 2007Journal of Clinical InvestigationOpen Access

Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure

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Population

Inducible transgenic mice with enhanced sarcolemmal L-type Ca2+ channel activity and other mouse models of…

Comparison

Enhanced Ca2+ influx via LTCC overexpression… vs Wild-type mice, single-transgenic controls, or…

Design

Preclinical

Follow-up

up to 12 months of age

Authors

HNHiroyuki NakayamaKagoshima University XCXiongwen ChenHuaihua University CBChristopher BainesUniversity of Missouri

Discussion

Member takes

Implication

Identifies modifiable necrotic pathways in cardiomyopathy models; leaves open translation to clinical heart failure therapy.

Key Points

The study investigates the role of necrosis in cardiac myocyte loss as a contributor to heart failure.
Inducible transgenic mice with enhanced sarcolemmal L-type calcium channel activity were used.
Ca2+ influx-induced necrosis was analyzed with the use of LTCC blockers and beta-adrenergic receptor antagonists.
Mechanistic studies included assessing the role of cyclophilin D and Bcl-2 in necrosis and heart failure progression.
Enhanced L-type calcium channel activity led to myocyte necrosis, heart failure, and premature death in mice.
Blocking LTCC or beta-adrenergic receptors prevented necrosis and heart failure progression.
Loss of cyclophilin D blocked necrosis and heart failure, while Bcl-2 overexpression did not mitigate heart failure associated with excess Ca2+ influx.

Structured PICO

Population

Inducible transgenic mice with enhanced sarcolemmal L-type Ca2+ channel (LTCC) activity (overexpression of the β2a subunit) and other mouse models of heart failure

Intervention

Enhanced Ca2+ influx via LTCC overexpression, with or without acute β-adrenergic receptor stimulation (isoproterenol), LTCC blockade (verapamil), β-adrenergic receptor blockade (metoprolol), antiapoptotic factor overexpression (Bcl-2), or loss of cyclophilin D (Ppif-/-)

Comparator

Wild-type mice, single-transgenic controls, or untreated double-transgenic mice

Outcome

Cardiomyocyte necrosis, cardiac hypertrophy, ventricular dysfunction, and premature death

Heart failure progression involves not only apoptosis but also mitochondrial-dependent necrotic loss of myocytes driven by Ca2+ overload and β-adrenergic receptor signaling.

Cite This Study

Nakayama et al. (2007) studied this question.

synapsesocial.com/papers/6a1fcb2e66f4632d4f6b45dd https://doi.org/10.1172/jci31060

Topics

Cardiomyopathy Heart failure HFrEF treatment

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Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

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