UC San Diego

Cardiovascular disease is the primary cause of morbidity and mortality in the United States. The majority of patients who survive an initial myocardial infarction (M.I.) do not have a positive prognosis due to the increased work load that is placed upon the heart and this is compounded by the inability to regenerate the lost myocardium. Heart failure therefore is at its essence a loss of cardiomyocytes. This problem has stimulated an intense research effort to develop the means to replace the damaged or dead cardiomyocytes with transplanted cells, such as human Embryonic Stem Cell Derived Cardiomyocytes (hESCDCs) or through expansion of putative adult cardiomyocytes, progenitors or stem cells. In the current study we utilized Invitrogen's microRNA (miR) microarrays to examine the miR profile of hESCDCs in order to identify novel miRs that regulate the process of differentiation to the cardiomyocyte lineage in addition to miRs that are involved in maintaining the proliferative capacity of immature hESCDCs. With the same tools we are also analyzing Neonatal Rat Ventricular Cardiomyocytes (NRVCs) that have been induced to re-enter the cell cycle through over-expression of components of the Notch pathway. Here, we are looking also for novel miRs that are involved in Notch replication of NRVC cell cycle, either as agonists or antagonists. Identification of such miRs could increase our understanding of cardiomyocytes cell cycle and might lead to strategies to increase the pool of cardiomyogenic cells for therapeutic purposes. From these microarrays, we have identified several miRs that are involved in the processes before mentioned and are therefore being characterized functionally by means of high throughput screens and other studies to determine relevant targets