Cell death in heart failure
1Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Insights
Heart failure (HF) involves complex cell death mechanisms. This review explores apoptosis, autophagy, and necrosis in pathological cardiac remodeling, offering insights into HF treatment.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Death Research
Background:
- Heart failure (HF) is a leading cardiovascular disease globally.
- Understanding pathological cardiac remodeling is crucial for HF prevention and treatment.
- Cell death pathways, including apoptosis, autophagy, and necrosis, play significant roles in HF.
Purpose of the Study:
- To review and summarize recent findings on the molecular mechanisms of cardiomyocyte cell death in heart failure.
- To clarify the roles of apoptosis, autophagy, and necrosis in pathological cardiac remodeling.
- To identify potential therapeutic targets for preventing and treating HF.
Main Methods:
- Literature review of recent studies on cardiomyocyte cell death in HF.
- Analysis of molecular mechanisms underlying apoptosis, autophagy, and necrosis.
- Synthesis of current understanding of cell death's role in cardiac remodeling.
Main Results:
- Apoptosis is a well-characterized programmed cell death.
- Necrosis, once considered uncontrolled, is now understood to be regulated.
- Autophagy, typically a survival mechanism, may contribute to cell death in specific HF contexts, though it can also be adaptive.
Conclusions:
- Cardiomyocyte cell death is a key factor in heart failure pathogenesis.
- Distinct cell death pathways (apoptosis, regulated necrosis, autophagy) have complex roles in HF.
- Further research into these mechanisms may reveal novel therapeutic strategies for heart failure.
Abstract:
Heart failure (HF) has become the dominant cardiovascular disorder in the Western world and Japan, so there is an urgent need to clarify the mechanisms governing pathological remodeling mediated through cell death, and to identify ways of preventing and treating HF. Historically, there are 3 types of cell death: apoptosis, autophagy and necrosis. Apoptosis, a form of programmed cell death, has been well characterized and the molecular events involved in apoptotic death are well understood. Necrosis is often defined in a negative manner: death lacking the characteristics of programmed cell death and thus accidental and uncontrolled. However, recent studies indicate that necrosis is tightly regulated. Autophagy is a cell survival mechanism that involves degradation and recycling of cytoplasmic components. In contrast to the other 2 mechanisms, autophagy may mediate cell death under specific circumstances. In fact, damaged cardiomyocytes that show characteristics of autophagy have been observed during HF. However, a recent study indicated that upregulation of autophagy in the failing heart is an adaptive response. This review summarizes recent findings regarding the molecular mechanisms of cardiomyocyte cell death in HF.
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