Different signaling pathways induce apoptosis in endothelial cells and cardiac myocytes during ischemia/reperfusion injury.

Abstract

Apoptosis contributes, with necrosis, to the cardiac cell loss after ischemia/reperfusion injury. The apoptotic cascade is initiated either by mitochondrial damage and activation of caspase-9 or by death receptor ligation and activation of caspase-8. In the present study, performed in the isolated rat heart exposed either to ischemia alone or ischemia followed by reperfusion, cleavage of caspase-9 was observed primarily in endothelial cells. Conversely, caspase-8 cleavage was only found in cardiomyocytes, where it progressively increased throughout reperfusion. Addition of a specific caspase-9 inhibitor to the perfusate before ischemia prevented endothelial apoptosis, whereas preischemic infusion of a specific caspase-8 inhibitor affected only myocyte apoptosis. Additionally, caspase-8-mediated BID processing was observed only during reperfusion. Production of tBID then sustains mitochondrial injury and perpetuates caspase-9 activation.

• Authors: Tiziano M Scarabelli, Anastasis Stephanou, Evasio Pasini, Laura Comini, Riccardo Raddino, Richard A Knight, David S Latchman
• Journal: Circulation research (Circ Res) Vol. 90 Issue 6 Pg. 745-8 (Apr 05 2002) ISSN: 1524-4571 [Electronic] United States
• PMID: 11934844 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BH3 Interacting Domain Death Agonist Protein
• Bid protein, rat
• Carrier Proteins
• Casp8 protein, rat
• Casp9 protein, rat
• Caspase 8
• Caspase 9
• Caspases

Topics

• Animals
• Apoptosis (physiology)
• BH3 Interacting Domain Death Agonist Protein
• Carrier Proteins (metabolism)
• Caspase 8
• Caspase 9
• Caspases (metabolism)
• Coronary Circulation
• Endothelium, Vascular (pathology)
• In Vitro Techniques
• Myocardial Reperfusion Injury (pathology, physiopathology)
• Myocardium (pathology)
• Organ Specificity
• Rats
• Signal Transduction (physiology)