Notch signaling activation contributes to cardioprotection provided by ischemic preconditioning and postconditioning.

Abstract

BACKGROUND:

Notch signaling is known to be activated following myocardial ischemia, but its role in cardioprotection provided by ischemic preconditioning (IPC) and ischemic postconditioning (IPost) remains unclear.

METHODS:

Lentiviral vectors were constructed to overexpress or knockdown N1ICD in H9c2 cardiomyocyte and rat heart exposed to ischemia reperfusion injury (IRI), IPC or IPost.

RESULTS:

Notch1 signaling was activated during myocardial IPC and IPost, and could enhance cell viability and inhibit apoptosis. Furthermore, activated Notch1 signaling stabilized mitochondrial membrane potential and reduced reactive oxygen species induced by IRI. The cardioprotection provided by activated Notch1 signaling resembled that of IPC and IPost, which was related to Stat3 activation and regulation of apoptosis related proteins. Furthermore, in langendorff heart perfusion model, activated Notch1 signaling restored cardiac function, decreased lactate dehydrogenase release and limited infarct size after myocardial ischemia.

CONCLUSIONS:

Notch1 signaling is activated and mediates cardioprotection provided by IPC and Ipost. Notch1 signaling may represent a potential new pharmacologic mimic for cardioprotection of ischemic heart disease.

• Authors: Xue-liang Zhou, Li Wan, Qi-rong Xu, Yong Zhao, Ji-chun Liu
• Journal: Journal of translational medicine (J Transl Med) Vol. 11 Pg. 251 (Oct 08 2013) ISSN: 1479-5876 [Electronic] England
• PMID: 24098939 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• RNA, Small Interfering
• Receptors, Notch
• STAT3 Transcription Factor
• L-Lactate Dehydrogenase

Topics

• Animals
• Apoptosis
• Cardiotonic Agents (metabolism)
• Cell Line
• Genetic Vectors
• Heart Function Tests
• In Vitro Techniques
• Ischemic Postconditioning
• Ischemic Preconditioning, Myocardial
• L-Lactate Dehydrogenase (metabolism)
• Lentivirus (metabolism)
• Mitochondrial Membrane Transport Proteins (metabolism)
• Mitochondrial Permeability Transition Pore
• Myocardial Ischemia (metabolism, pathology, physiopathology)
• Myocytes, Cardiac (metabolism, pathology)
• Necrosis
• Phosphorylation
• Protein Structure, Tertiary
• RNA, Small Interfering (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Notch (chemistry, metabolism)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction