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Poster Presentations
Day 2, June 23（Mon.）
Room P (Maesato East, Foyer, Ocean Wing)
- 2P-PM-15
Pleckstrin Serves as a Prognostic Marker for COVID-19 and Promotes Pro-Thrombotic Symptoms via ERK Activation
(1HKBU, 2HKU)
oLi Zhong1, Lin Zhu1, Runhong Zhou2, Zhiwei Chen2, Zongwei Cai1
Unlike other viral infections, the SARS-CoV-2 virus significantly increases the risk of thrombosis, constituting a significant risk and disease burden to over 60 million COVID-19 survivors worldwide. Understanding the mechanisms underlying the pro-thrombotic event is essential for elucidating the pathological features of COVID-19 and addressing the development of long COVID. This study investigated the longitudinal proteomic profiles of 135 serum samples from 29 COVID-19 patients and 15 uninfected individuals. Significant platelet activation and pro-thrombotic protein profiles were discovered in patients. By comparing mild and severe cases over time, pleckstrin (PLEK) emerged as an early prognostic marker for severe symptoms associated with microthrombosis. Data mining of RNA sequencing data from three additional cohorts from the public database corroborated PLEK's role in severe COVID-19 symptoms and thrombosis. In vitro models indicated that PLEK promoted the expression of proinflammatory cytokines and thrombotic markers via activating the ERK signaling pathway. In vivo experiments using a hamster model confirmed that PLEK levels correlated to virus-induced injuries, and supplementation of exogenous PLEK exacerbated the thrombotic-like injuries. Collectively, PLEK is proposed as a mediator and prognostic marker for COVID-19-induced microthrombosis, shedding light on potential risk stratification and management strategies for all COVID-19 survivors.