| Center for Cardiovascular Cell Therapy, Louisville, KY |
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Center for Cardiovascular Cell Therapy Mission: To study the basic biology and the clinical applications of therapies based upon adult stem/progenitor cells for cardiovascular disease. Director:
Roberto Bolli, MD Background of Director: Dr. Bolli’s research involves the mechanism of the late phase of ischemic preconditioning (PC). Late PC is the phenomenon whereby exposure of the heart to a brief ischemic stress induces a delayed, relatively sustained protective response against subsequent ischemic injury, which is fully manifest 24-72 h later. Because late PC is long lasting and results in a powerful protection against both myocardial infarction and myocardial dysfunction (i.e., stunning), it has great potential clinical implications. Using a conscious rabbit model of late PC, Dr. Bolli has shown that oxyradicals are involved in late PC, and that nitric oxide synthase (NOS) and its product nitric oxide (NO) play key roles in the mechanism of late PC. Specifically, Dr. Bolli has demonstrated that NO produced from a constitutive NOS (probably eNOS) acts as the trigger for late PC on day 1, while NO produced from iNOS acts as the mediator of late PC on day 2. More recently, using an open-chest mouse model of late PC and mice bearing gene targeted ablations of iNOS, Dr. Bolli has shown that iNOS plays an obligatory role in late PC and that NO-donors are able to induce late PC against both myocardial stunning and infarction. Ongoing research includes clinical studies of NO-donors to induce late PC in patients with coronary artery disease, and collaborative studies with molecular biologists in the Division to elucidate the cellular and molecular mechanisms that underlie the late phase of ischemic PC. The long-range goals of Dr. Bolli’s research are to elucidate the cellular mechanism of late PC, and to use this knowledge to reproduce this cardioprotective phenomenon in the clinical setting via pharmacologic and/or gene therapeutic means. |
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