A disorder of platelet function is known thrombocytopathy which is related to the development, advancement, treatment and prognosis of many diseases, such as cancers, stroke, and sepsis. Platelets are made in bone marrow and have no nucleus, but do contain structures called granule cell fragments. Inflammation and immune systems are associated with the multitude of interactions between leukocytes, endothelial cells, and platelets. On the other hand, platelets are affected by increased inflammation. When activated, platelets produce microparticles that have many pathophysiological functions including initiation and exacerbation of inflammation. The potential for platelets to interact with other cells in the circulation and on the vascular surface is enhanced by the extremely large concentration of platelets in blood in their highly reactive state.
Previously we showed that the inflammation which increased in acute ischemic stroke patients with apoptotic changes occurring in platelets may contribute to the formation of thromboembolism (1). Furthermore, a variety of platelet abnormalities have been described in atherothrombotic events in ischemic stroke. Therefore anti-platelet drugs and anticoagulants are in clinical use for stroke prevention. Currently there are no clinical parameters that accurately prevent the platelet activation of stroke. However, we can assess platelet number and size (mean platelet volume; MPV), platelet morphology, activated clotting time (ACT), bleeding time (BT), and quantitate the presence or absence of platelet membrane glycoproteins using light transmission aggregometry and flow cytometric.
Antiplatelet agents are available for prevention and treatment of acute ischemic stroke (2,3). Our project is investigating the proteomic profile of platelets and their changing functions in acute ischemic stroke patients using the LC-MS/MS system (UPLC-ESI-qTOF-MS).
Proteomic profiling of platelets obtained from the stroke patients resulted in identification of 500 proteins. Using Progenesis LC-MS software V4.0 (Nonlinear Dynamics) and Ingenuity Pathway Analysis, we found that 83 of these proteins were found to be differentially expressed in patients. These differentially expressed proteins were involved in various processes such inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function, and nucleic acid metabolism. On the other hand, this project is the first report providing a global proteomic profile of platelets from stroke patients.
So, what can do for prevention of stroke? Our data showed that inflammation caused by stroke changed platelet cellular protein interactions in patients. These results provide an insight into the proteins that are involved as platelets respond to inflammation during ischemic stroke. The results may help in new drug design for antiplatelet therapy and contribute to new gene therapies in the future.
References:
1- Cevik et al, Mol Biol Rep 2013, http://www.ncbi.nlm.nih.gov/pubmed/24057255
2- Jiang et al, Drug Discov Today, 2014, http://www.ncbi.nlm.nih.gov/pubmed/24931218
3- Hong et al, J Clin Neurol, 2014, http://www.ncbi.nlm.nih.gov/pubmed/25045370