In June 2019, a study published in the journal Circulation by Professor Du Jie's team at Beijing Anzhen Hospital affiliated to Capital Medical University showed that s100a8/a9 is a potential therapeutic target and early warning marker for myocardial ischemia/reperfusion injury. The study elucidates the pathogenic mechanism of s100a8/A9 and its potential clinical diagnostic applications.
Myocardial ischemia/reperfusion injury is the main event affecting the effect of coronary intervention therapy or bypass surgery in patients with acute myocardial infarction, and there is still a lack of effective intervention measures for myocardial ischemia/reperfusion injury, so it is of great scientific significance and clinical value to clarify the molecular mechanism of myocardial ischemia/reperfusion injury leading to cardiac injury, providing potential new targets for clinical prevention and treatment.
Through the dynamic transcriptome, Professor Du Jie's team found that s100a8/a9 was rapidly elevated in the early stages of myocardial ischemia/reperfusion injury. S100a9 knockout and overexpression experiments in animals confirmed that s100a8/a9 is the key initiator of myocardial ischemia/reperfusion injury.
Further mechanistic studies suggest that s100a8/a9 downregulates the gene expression of the mitochondrial complex i subunit ndufs by inhibiting the tlr4/erk-mediated pgc-1α/nrf1 signaling pathway, thereby inhibiting the function of the mitochondrial complex i, causing mitochondrial dysfunction, leading to myocardial cell death, and promoting the development of myocardial ischemia/reperfusion injury; s100a9 neutralizing antibody therapy can significantly slow down myocardial ischemia/reperfusion injury.
In a subsequent clinical registration study, the team found that 1 day after coronary intervention, elevated serum s100a8/a9 levels were significantly associated with the occurrence of long-term cardiovascular adverse events in patients with acute myocardial infarction.
After publication, the results were validated by an independent research team from Lund University in Switzerland, published in the European Journal of the Heart in July.
At present, Professor Du Jie's team has comprehensively carried out the work of early warning and intervention treatment of S100a8/A9 in the interventional treatment of acute myocardial infarction: the s100a8/a9 detection kit and monoclonal therapy antibody have been developed, and the clinical research of "s100a8/a9 early warning after acute myocardial infarction pci" has been carried out in beijing Anzhen Hospital as the center and in conjunction with many hospitals.
Associate Professor Yulin Li is the first author of this paper, and Professor Du Jie, Associate Professor Yulin Li and Professor Ma Xinliang of Jefferson University are co-corresponding authors.
Source: Capital Medical University News Network
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