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Apoptosis in cardiac diseases: stress- and mitogen-activated signaling pathways
1Cardiovascular Disease Research, DuPont Pharmaceuticals Corporation, Wilmington, DE 19880-0400, USA.
Insights
Apoptosis, programmed cell death, plays a role in heart disease. Understanding protein kinase pathways like stress-activated protein kinases (SAPK) and mitogen-activated protein kinases (MAPK) in cardiomyocyte apoptosis offers new therapeutic avenues.
Area of Science:
- Cardiovascular Biology
- Cellular Signaling
- Molecular Medicine
Background:
- Apoptosis, or programmed cell death, is a critical cellular process observed in various human cardiac diseases, including heart failure and myocardial infarction.
- Key stimuli triggering cardiomyocyte apoptosis include oxidative stress, inflammatory cytokines (FAS/TNF alpha), physical/chemical stressors, ceramide, and angiotensin II.
- Cardiomyocyte apoptosis can exacerbate heart failure progression, arrhythmias, and cardiac remodeling, highlighting its significance in cardiovascular pathology.
Purpose of the Study:
- To review the role of protein kinase signaling pathways in cardiomyocyte apoptosis.
- To emphasize the involvement of stress-activated protein kinases (SAPK) and mitogen-activated protein kinases (MAPK) in this process.
- To explore the therapeutic potential of targeting these pathways for cardiac ailments.
Main Methods:
- Literature review focusing on molecular mechanisms of apoptosis in cardiomyocytes.
- Analysis of signaling pathways, particularly SAPK and MAPK systems.
- Synthesis of evidence linking cardiomyocyte apoptosis to cardiac disease progression and therapeutic interventions.
Main Results:
- Apoptosis is a significant contributor to the pathogenesis of diverse cardiac conditions.
- Specific protein kinase pathways, including SAPK and MAPK, are central regulators of cardiomyocyte apoptosis.
- Numerous molecular targets within these pathways present opportunities for novel therapeutic strategies.
Conclusions:
- Targeting protein kinase signaling pathways involved in cardiomyocyte apoptosis may offer effective treatments for heart disease.
- Further research into SAPK and MAPK systems could lead to innovative pharmacologic interventions.
- Understanding the molecular basis of apoptosis is crucial for developing new therapies for cardiovascular ailments.
Abstract:
Apoptosis is a form of cell death that involves discrete genetic and molecular programs, de novo protein expression and a unique cellular phenotype. Evidence for the existence of apoptosis in the human heart has been reported in various cardiac diseases, including ischemic and non-ischemic heart failure, myocardial infarction and arrhythmias. Among the most potent stimuli that elicit cardiomyocyte apoptosis are: oxygen radicals (including NO), cytokines (FAS/TNF alpha-receptor signaling), stress conditions (chemical or physical, e.g., radiation), sphingolipid metabolites (ceramide) and autocoids, e.g., angiotensin II. Apoptosis of cardiac myocytes may contribute to progressive pump-failure, arrhythmias and cardiac remodeling. The recognition of numerous molecular targets associated with cardiomyocyte apoptosis may provide novel therapeutic strategies for diverse cardiac ailments, as recently suggested by pharmacologic studies in experimental animals. This review paper is aimed to highlight the role of protein kinase signaling pathways in apoptosis with special attention to the stress-activated protein kinases (SAPK) and mitogen-activated protein kinases (MAPK) systems.