Grant: Operating Grant - Priority Announcement: Blood Utilization and Conservation

The circulating blood platelet is the central player involved in the thrombotic processes that underlie the often fatal complications of cardiovascular diseases (CVD) (e.g., myocardial infarction and stroke), which accounted for 48% of all noncommunicable disease deaths in 2008 (www.who.int). Platelets are also involved in the maintenance of hemostasis, and platelet concentrates are transfused to patients with a low platelet count in order to normalize hemostatic conditions and prevent health complications. In 2009, we reported that platelets contain a vast repertoire of microRNAs, which are known to finely tune gene expression, mainly through repression of messenger RNA (mRNA) translation into proteins. MicroRNAs may regulate 60% of the genes in humans, suggesting that microRNA (de)regulation of gene expression may play a significant role in human health and diseases. A year later, Dr. Eric Boilard (Co-Applicant) reported that platelets release microparticles (MPs; small vesicles of 0.1-1 micron in diameter) upon activation with collagen, along a process that amplifies inflammation. Combining our expertise, we have recently shown that activated platelets can deliver mRNA regulatory Argonaute 2 (Ago2)-miR-223 complexes to endothelial cells through the release of microparticles (MPs). More recently, Dr. Boilard's team made a surprising discovery that prompted us to hypothesize that platelets release different forms of bioactive MPs that can be delivered to other cells of the circulatory system and induce changes in recipient cell programming and function, at least in part, through heterotypic regulation of gene expression. This proposal is expected to (i) bring new knowledge and perspectives on the release, delivery and cell programming effects of platelet-derived MPs, (ii) illustrate the magnitude and complexity of intercellular communications in the circulatory system, and (iii) prompt reassessment of blood utilization/conservation policies.