Recently, the Department of Cardiology of Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine published a research paper in the european heart journal (European Heart Journal), which found the circadian rhythm mechanism with high early morning incidence of clinical thrombotic events, which provided new cognitive and intervention targets for the occurrence of clinical thrombotic events.
Thrombotic events are a common hazard of chronic diseases such as cardiovascular disease and tumors. Existing cognition cannot fully explain the clinical findings of the high incidence of thrombotic events in the early morning, and platelet drug research and development is an important need of clinical medicine.
Researchers have found in clinical studies that human platelet aggregation and thrombosis have a morning peak phenomenon. The presence of a special, circadian oscillating circadian clock nucleus receptor Rev-erbα in healthy human platelets drives the morning peak phenomenon of human platelet aggregation and thrombosis. Circadian clock nucleus receptor activation has diurnal oscillations in platelets in hypercoagulable patients and plays a key role in thrombosis.
Using a variety of preclinical thrombotic models, the researchers revealed that the circadian clock nuclear receptor Rev-erbα is the co-driving active factor of platelet activation and thrombosis in thrombotic events, and as the mother cell of platelets in the human body, the circadian oscillation of the circadian clock in mature megakaryocytes of bone marrow is the original driving mechanism of the morning peak phenomenon of acute thrombotic events. On this basis, through mass spectrometry analysis, protein network interaction analysis and immunoprecipitation verification, the researchers discovered a new signaling pathway for platelet activation. The circadian clock nuclear receptor Rev-erbα, as a key gene in the rhythm-regulated loop, is a special member of the nuclear receptor family and a potential target for drug intervention. In order to promote clinical translation, the researchers used small molecule-protein docking technology to find that a Rev-erbα-specific inhibitor can inhibit this new activation pathway, significantly inhibiting human platelet activation and in vitro thrombosis.
The Department of Cardiology of Renji Hospital has a profound heritage, and is a national clinical key discipline, a 211 key discipline of the Ministry of Education, the first batch of master's and doctoral degree awarding points in china, and the first batch of cardiovascular specialist training bases in china. The discipline now has a number of outstanding young talents such as winners of the National Outstanding Youth Fund, Jiang Scholars Distinguished Professor of the Ministry of Education, leading talents of the National Ten Thousand Talents Program, and young and middle-aged leading talents of the Ministry of Science and Technology. The first author of the paper is Dr. Shi Jianfeng, Dr. Tong Renyang and Master Zhou Meng, and the corresponding author is Professor Bu Jun. The project has been funded by the National Science Foundation for Outstanding Young People and the Key Projects of the National Natural Science Foundation of China.
(China Daily Shanghai Branch)