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Prof. Johannes Waltenberger,
Regional myocardial ischemia limits cardiac function and prognosis of the patient. The therapeutic stimulation of collateral artery growth, defined as therapeutic angiogenesis/arteriogenesis can improve the blood flow to the ischemic myocardium.
Bench to Bedside - Basic Science
Although recent clinical trials on therapeutic angiogenesis/arteriogenesis have shown disappointing results, Dr M. Simons, Dartmouth College, USA indicated a number of key issues, which can explain the lack of efficacy in patients. Efficacy of therapeutic arteriogenesis depends not only on proper drug delivery. Recent genetic data indicate that there are certain mutations or circulating inhibitors, which are associated with a resistance to development of collateral vessels. In addition, metabolic disorders such as diabetes induce cellular defects that could explain the unresponsiveness to growth fator treatment. It will be crucial for the further development of therapeutic angiogenesis/arteriogenesis to identify novel biomarkers to predict whether a certain patient will respond to growth factor treatment.
Focusing on the efficiency of gene therapy, Dr. C. Sylven from Stockholm, SE, elaborated on the perspectives of viral gene transfer. Latest generation adenoviral vectors will be more effective and may guarantee a controlled, prolonged and restricted transgene expression. Improvements in delivery can be expected from gene therapy stents capable of regional or systemic delivery.
Therapeutic angiogenesis/arteriogenesis can be achieved using cell therapy. Dr. R. Braun-Dullaeus from Dresden University, DE highlighted the importance of local inflammation for efficient homing of monocytes, which are key mediators of arteriogenesis. The complexity of cell therapy was highlighted by Dr. J. Bartunek from Aalst, BE. Cell therapy for STEMI is still experimental and depends not only on homing of bone marrow-derived cells, but also on their number, function and on the mode of processing.
Major limitations of previous approaches to develop therapeutic angiogenesis / arteriogenesis for inducing collateral vessels have been identified and novel solutions are about to be tested. Individualized and optimized approaches will eventually help to make therapeutic angiogenesis/arteriogenesis an efficient and predictable therapy.
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Therapeutic angiogenesis/arteriogenesis Symposium - Bench to Bedside
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