Nrf2 Inducers as Pharmacological Agents for Cardiac Protection?

Limiting cardiac injury and reducing adverse events in myocardial infarct patients have been a topic of extensive research for decades. The effectiveness of MI treatment has improved dramatically over the past 40 years so that it is less common for a patient to die from MI. Preventive care or treatment for early MI patients includes Coronary Artery Bypass Graft (CABG). Standard treatments of symptomatic patients consist angioplasty or Percutaneous Intervention (PCI) in combination with thrombolytic agents, vasodilators, b-blockers, and statins. Reperfusion by CABG or PCI is essential to salvage myocardial tissues from ischemic injury. However, nearly all bypass patients and about 30% of angioplasty patients show elevated cardiac troponins in the blood postoperatively. Myocardial cell death remains detectable even when patients appear to have recovered and resumed normal life. Cell death contributes to cardiac remodeling and development of heart failure over time. Pharmacological agents that can reduce cell death and promote cardiac repair are desirable for the next phase of cardiac protection. Inducers of Nrf2 transcription factor may serve the purpose. Nrf2 encodes a transcription factor Nrf2 best known for regulating the expression of antioxidant and detoxification genes. Genome wide profiling studies have revealed that Nrf2 also controls for the genes participating in cell signaling, transcription, anabolic metabolism, cell proliferation, and extracellular matrix remodeling. Gene knockout approaches have demonstrated a universal cytoprotective feature of Nrf2. Experimental data will be presented to support the potential of dialing up Nrf2 pathway for cardiac protection and prevention of heart failure following MI.