Stem cells in heart failure and pulmonary hypertension can help restore normal organ structure and function. Leading lung disease and heart failure expert explains how science helps to develop effective treatments. Your research focuses on how blood vessels and lungs change in disease. Dr. Anton Titov, MD. You show that inflammation in lungs leads to change in vascular architecture. The lung and the blood vessels undergo a remodeling process. You also have a mouse model that mimics closely pulmonary arterial hypertension. How does your research help people with lung disease? Dr. Anton Titov, MD. What are the current directions of your research in pulmonary arterial hypertension and other lung vascular diseases? Dr. Anton Titov, MD. Dr. Aaron Waxman, MD. We have learned a lot from the work we have done here. We learned about the role of inflammation in driving vascular remodeling. We have looked at several aspects of inflammation. We have used a number of animal models of pulmonary arterial hypertension. You mentioned the mouse model. These mice are an IL-6 over-producers that remodeled their lung blood vessels much like human disease. Although it is still not a clean model of human disease. Dr. Aaron Waxman, MD. We have developed a large animal model in collaboration with Dr. Jane Leopold in cardiology. We used a pig model of right ventricular heart failure. We can tie off the inferior pulmonary vein in a pig. That drives a timed remodeling of the pulmonary vascular bed and in the right side of heart. We have been able to use that as a model of progressive pulmonary vascular remodeling. We could do an accurate timing of right-sided heart dysfunction. It eventually becomes a right-sided heart failure. Dr. Aaron Waxman, MD. We have been able to look at administering stem cells using an intracoronary artery approach. We showed a viability of those stem cells. That right-sided heart failure model may also allow us to ask the question about medical devices. Could we put in a ventricular assist device in the setting of right heart failure? Dr. Anton Titov, MD. Would a medical device help remodel the vascular bed towards normal state. Could a right ventricular assist device support the right ventricle’s function? Dr. Anton Titov, MD. There are also questions about pulsatile blood flow versus non-pulsatile flow. There may be a benefit to non-pulsatile blood flow in the pulmonary vascular bed. But let’s get back to your question about how it has affected how we treat patients. Dr. Aaron Waxman, MD. We now are starting to do clinical trials in anti-inflammatory treatments of pulmonary artery hypertension. This includes anti-IL-6 medications. It also includes medications that affect targets to the IL-6 receptors and downstream effectors of those receptors. There are also stem cell methods to treat right-sided heart failure. There are even implantable device-based methods to treat right ventricular heart failure. It is certainly very interesting. Because your research has direct clinical implications. It can help to understand the pathophysiology of the lung disease better for patients with lung diseases.
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