Dr. Rui-Ping Xiao is the Dean of the College of Future Technology at Peking University and the Peking University Chair Professor. Dr. Xiao’s research has been focused on cardiovascular and metabolic diseases, with a major emphasis on a translational approach to take bench discoveries into clinically relevant situations. Ongoing research directions include signaling pathways involved in metabolic syndrome and associated cardiovascular complications. Currently, Dr. Xiao serves as a Council Member of the International Society of Heart Research and an Associate Editor of the New England Journal of Medicine and an Editorial Board Member of multiple international top journals.
The therapeutic options for diabetic patients with cardiovascular complications are limited, highlighting an outstanding unmet medical need. MG53 (also named TRIM72) is a myokine with cell protective effects. However, MG53 also promotes insulin resistance and metabolic disorders via its E3 ligase activity. Here, we show that in diabetic mice, recombinant E3-dead MG53 mutants (C14A or S255A) effectively protects the heart from ischemia/reperfusion (I/R) injury without metabolic side-effects, whereas wild-type MG53 profoundly exacerbates hyperglycemia and I/R-induced myocardial injury and mortality, especially in mice with advanced diabetes. Consistently, MG53 C14A knock-in mice are protected against high fat diet (HFD)-induced metabolic disorders, while IPC can still trigger cardioprotection in the C14A knock-in mice. These in vitro and in vivo data indicate that E3-dead MG53 mutants not only preserves myocardial protective functions in diabetic individuals, but also defends mice against metabolic dysfunctions incurred by HFD, demonstrating their therapeutic potential in treating diabetes-associated cardiovascular complications.