PHA-Funded Study Explores Role of MIF in Hypoxia-Induced Pulmonary Vascular Remodeling

Study aims to find a new therapeutic target for PH

Dr. Yinzhong Zhang
Research has long been the key to unlocking PH mysteries, and each year new discoveries occur that move us further along in our understanding and treatment of PH. Dr. Yinzhong Zhang of the Feinstein Institute for Medical Research is doing his part to propel PH research forward. Dr. Zhang was a 2008 recipient of the PHA/American Heart Association Post-Doctoral Fellowship Award for his research project entitled “Role of Macrophage Migration Inhibiting Factor (MIF) in Hypoxia-Induced Pulmonary Vascular Remodeling.”

As Dr. Zhang explains, “Hypoxia can induce pulmonary vascular remodeling, which is an important mechanism in PH formation and processing; it remains unclear how the hypoxia causes pulmonary vascular remodeling. Since PH patients have increased MIF and MIF increase cell growth, hypoxia can drive cells to produce more MIF, and since the lungs are a major source of MIF, we hypothesize that MIF may be an important mediator between hypoxia and PH. In my study, I have used an hypoxic mice model and an hypoxic cell proliferation model to study the role of MIF in hypoxic cell proliferation and finally PH formation.”

Through this study, Dr. Zhang hopes to discover a new therapeutic target to help end this devastating disease. “So far I have found that hypoxia can induce both MIF expression and cell proliferation. A blockade on MIF by an inhibitor can dose dependently inhibit hypoxia-induced cell proliferation. If the cells are genetically deficient in MIF gene, they do not show hypoxic cell proliferation. However, these cells can regain the hypoxic cell proliferation by the supplement of MIF, which was achieved by giving the condition medium from non-deficient cells,” Dr. Zhang says. “In addition, MIF inhibitor significantly alleviates hypoxia-induced PH in our animal model. This data clearly shows that MIF is an important mediator between hypoxia and pulmonary hypertension and has a potential of being a new therapeutic target for PH.”
Past research in PH aided Dr. Zhang's efforts

Dr. Zhang's current research builds upon the work of other researchers. Before Dr. Zhang joined Dr. Edmund J. Miller's lab at the Feinstein Institute for Medical Research as a Postdoctoral Fellow in 2007, this lab “had collaborated with Dr. Talwar, a pulmonary physician specializing in PH,” Dr. Zhang says. “Our lab’s previous data showed that PH patients have increased levels of MIF. Based on this data, I was very interested in whether MIF plays a role in hypoxia-induced pulmonary vascular remodeling. The idea finally formed into a Fellowship application, and I was fortunately funded by PHA.”

Dr. Zhang’s interest in PH began when he was working at Peking Union Medical College Hospital (PUMCH), which is one of the top hospitals in China. While working as an anesthesiologist at PUMCH from 2003–2006, he encountered many patients who required anesthesia, but their cases were complicated by the presence of PH. During this time, he also joined a group of medical professionals performing surgical therapy for a special kind of PH, chronic thromboembolic pulmonary hypertension (CTEPH), and he assisted with the anesthesia for eight CTEPH surgeries. Dr. Zhang published a paper on the anesthesia management for CTEPH surgeries and gave a presentation on the topic to his department. In order to prepare for the surgeries, the paper and the presentation, Dr. Zhang not only researched but also connected with PH patients. “Through my contact with PH patients, I came to understand their suffering. I think these experiences initially sparked my interest in PH,” he says.
PHA's efforts inspire Dr. Zhang's work

In addition to his research, Dr. Zhang participates in PHA events, including PHA's 9th International PH Conference and Scientific Sessions in Garden Grove, Calif., this past June. “I was deeply touched by the PH patients,” he says. “I think the highlight was the fashion show put on by the patients. Their love of life drives me to work hard on my research, and I hope my results can really help them in the future.”

PHA is proud to support the work of Dr. Zhang and all the researchers who work each and every day to advance the treatment of PH. PHA’s research program has committed more than $9 million for PH research through partnerships with the National Heart, Lung and Blood Institute, the American Thoracic Society and the American Heart Association. PHA has supported 44 outstanding researchers through three independently reviewed cutting-edge research programs to date.