Division of Cardiovascular Diseases Strategic Plan
Goals in Cardiovascular Clinical Problems or Disease States
2.4e. Develop effective therapies for protecting the heart from ischemia and reperfusion injury
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About 500,000 people die each year in the U.S. as a result of ischemic heart disease, the underlying cause of most cases of acute MI, heart failure, arrhythmias, and sudden cardiac death. As the population ages and the prevalence of major risk factors such as obesity and diabetes increases, the public health burden caused by ischemic heart disease will likely increase significantly. Potential therapies that protect the heart from injury occurring during ischemia and reperfusion are likely to improve both short- and long-term outcome in these patients. Insights gained in this area may help optimize organ preservation or tolerance to ischemic insult.
Strategies to Accomplish this Goal May Entail:
- Clarify the molecular mechanisms responsible for acute and chronic cardioprotection against ischemia and reperfusion injury that is induced by preconditioning and postconditioning strategies.
- Identify genetic variants associated with enhanced protection.
- Investigate the contribution of mitochondrial alterations to cardioprotection using a systems biology approach.
- Determine the impact of diabetic insult on oxidative stress and the initiation of apoptosis in cardiac mitochondrial subpopulations.
- Integrate knowledge emerging from the mitochondrial proteome to predict and understand its phenotype and functioning during normal, acute and chronic ischemic conditions as well as in the cardioprotected state.
- Develop, refine, and utilize imaging to better identify the region of myocardium at risk of ischemia/reperfusion injury.
- Develop nanotechnology methods to target delivery of cardioprotective therapies.
- Identify biomarkers for populations acutely at-risk for ischemic and reperfusion injury, including biosensors and monitors for adequate tissue perfusion.
- Perform preclinical evaluation of promising cardioprotective interventions in appropriate animal models.
- Investigate the impact of gender differences, aging, and comorbidities (e.g. diabetic and metabolic CV complications) as well as the concurrent use of medications with possible anti-ischemic properties, on the effectiveness of specific cardioprotective interventions and the manner of treatment strategies in clinical practice.
- Investigate the use of therapies found promising in preclinical studies with clinically relevant endpoints in randomized, well-controlled, double-blinded trials.