Ultrastructural definition of apoptosis in heart failure

Area of Science:

• Cardiovascular Biology
• Cellular Pathology

Background:

• Cardiac myocytes exhibit multiple cell death pathways, including apoptosis, oncosis, and autophagy.
• Understanding these mechanisms is crucial for addressing heart failure.
• Apoptosis involves nuclear fragmentation and apoptotic bodies, with clearance by macrophages without inflammation.

Purpose of the Study:

• To describe the morphological characteristics of cardiac myocyte death.
• To investigate the prevalence and significance of apoptosis, oncosis, and autophagy in failing human hearts.
• To explore potential shared therapeutic strategies for preserving myocyte integrity.

Main Methods:

• Light and electron microscopy to visualize morphological changes.
• Immunoelectron microscopy for detailed analysis of apoptotic markers (cytochrome c, TUNEL, annexin V).
• Observation of myocyte death features in human decompensated hearts.

Main Results:

• Apoptosis is characterized by nuclear fragmentation and apoptotic bodies, cleared without inflammation.
• Oncosis presents distinct morphological features and can coexist with apoptosis, especially in ischemic conditions.
• Autophagy, a defense mechanism, can lead to necrosis if lysosomal removal is impaired.
• While late-stage apoptosis and autophagy are rare in failing hearts, early apoptotic and autophagic changes are present in viable myocytes across various etiologies.

Conclusions:

• Morphological features of apoptosis, oncosis, and autophagy can coexist in cardiac myocytes.
• Early signs of apoptosis and autophagy are detectable in viable myocytes of failing human hearts, irrespective of etiology.
• The shared pathways of myocyte death suggest that therapeutic strategies targeting these mechanisms could preserve myocyte integrity in heart failure.