A Look Inside the Acute Aortic Dissection Project

Acute Aortic Dissection (AAD) is the most common thoracic aortic emergency and may be rapidly fatal without early diagnosis and appropriate management. It is highly lethal, and an untreated type A dissection has a mortality rate of 1-2% per hour after the onset of symptoms. Surgical repair can transform the high mortality risk to an 80-90% chance of survival, and shortening the time from onset of symptoms to surgical treatment may greater reduce mortality rates.  However, evidence suggests that in the United Sates, 50% of patients have a time to diagnosis of more than 15 hours after the patients arrive at the hospital. Thus, there is a critical need for AAD rapid diagnostic tools.
 
In 2013, the Joint Institute funded a research project “Identify Smooth Muscle Cell Specific Protein as Biomarkers for Early Diagnosis of Acute Aortic Dissections,” which aims to identify proteins in the serum of AAD patients as candidate biomarkers for AAD (since no ideal biomarkers currently exist), thereby providing the critical early diagnosis to improve patients’ chances of survival.
 
According to Dr. Bo Yang, Assistant Professor of Cardiac Surgery, UMMS, and co-investigator on the project, “The incidence of AAD is relatively low compared to acute coronary syndrome. In the US, if a center performs more than 13 AAD surgeries per year, it is considered to be an AAD high volume center.”  He adds, “the advantage of the JI collaboration is that both the University of Michigan Health System (UMHS) and Peking University Health Science Center (PUHSC) have access to large populations of AAD patients and research infrastructure to perform all proposed experiments.”
 
The UMHS Cardiovascular Center treats approximately 50 AAD patients each year, while PUHSC Third and other affiliated hospitals conduct 100-200 AAD surgeries annually. Both institutions also have the proteomics core facilities and laboratory support necessary to measure smooth muscle cell (SMC)-specific proteins in the serum.
 
Dr. Yang is very satisfied with the progress at UMMS and with the research partnership. “We are very glad to collaborate with Dr. Zhe Zhang’s team,” shares Dr. Yang. “Dr. Zhe is a great partner and we communicate on a weekly basis.”  “The data analysis of proteomics at UM has been completed,” he continues, “and the research team identified 5 target proteins as potential biomarkers of AAD. The PUHSC team will now conduct the proteomics study and confirm the target proteins.”

Investigators from both institutions formed a collaborative relationship in 2011 when Dr. Zhe Zhang visited UMHS to observe adult cardiac surgery cases and cardiac transplantation surgery. Dr. Zhe Zhang is Associate Professor of Cardiac Surgery Department, PUHSC Third Hospital, and serves as the PUHSC co-investigator for the project.
 
 “The JI project offers a great opportunity for both institutions to access a larger patient population,” Dr. Zhe points out. “In addition, the collaboration allows our teams to learn how to do research following standardized procedures, including IRB submission and protocol development. Following a standardized process ensures a reliable and accurate result,” he explains. “If it is possible, I would like to send my graduate students to UMMS and learn how research is conducted in the United States.”
 
There were some challenges in the early stages of the project; for example, the time between the onset of symptoms and blood sample collection was much longer than expected at PUHSC. But through efficient communication between the two teams, the Co-PIs modified the methodology by collecting the samples at several time points and creating the curve to observe the change of related protein levels, which solved the problem.
 
Dr. Zhang also mentions his appreciation to the JI platform. In addition to the research collaboration, Dr. Zhang also appreciates the opportunity the JI provides to observe cardiac surgeries in the US. In August 2015, he visited Ann Arbor and met Dr. Frank Pagani, Professor of Cardiac Surgery, and discussed possible implantation of the first Heart Disease and the Left Ventricular Assist Device (LVAD) in China. If this is achieved, it would be extremely exciting news for the Chinese cardiac surgery society and would, ultimately, contribute to patients who are waiting for heart transplant.
 
Should the JI project be successful, the partners will generate crucial preliminary data to support grant applications for further clinical study with a larger number size through the NIH (USA) and the National Science Foundation (China).