Understanding How Inflammation Contributes to Cardiovascular Disease

Matthew Feinstein, ’11 MD, ’17 MSc, is an associate professor of Medicine in the Division of Cardiology, of Preventive Medicine in the Division of Epidemiology, and of Pathology. He is also the director of Northwestern's Clinical and Translational Immunocardiology Program and director of medical student research at Feinberg.  

Feinstein’s research focuses on how inflammation can cause and accelerate cardiovascular diseases, as well as how dynamic immune cell responses can modulate these inflammatory responses.

What are your research interests? 

My research focuses on inflammation in cardiovascular disease. Specifically, I am interested in how we can better understand dynamic human immune responses that make some people more or less prone to inflammation, how common risk factors—such as high cholesterol and high blood sugar—affect this, and how uncontrolled, problematic inflammation can lead to cardiovascular diseases like heart attack and heart failure. 

What is the ultimate goal of your research? 

The ultimate goal of this work is to determine precise ways to modulate inflammation to prevent and treat heart and vascular disease in humans.   

How did you become interested in this area of research? 

I became interested in this through a combination of clinical and research experiences. Clinically, we are very good at defining and treating some risk factors that we know cause heart and artery disease, like high cholesterol. Yet, inflammation kept coming up time and again as a key factor in much of the heart and artery disease that remains poorly addressed by our current clinical approaches. Beyond identifying this as an area of clinical and scientific need, I also just find it incredibly interesting. We all need some inflammation, as it’s what our immune systems do in response to various triggers. When we have a cold, a virus acts as this trigger and our immune cells (white blood cells) create an inflammatory response to clear it. Yet there are plenty of times our immune system responds to triggers in a way that leads to harmful and sustained inflammation, resulting in temporary or lasting damage to our tissues. For instance, extra cholesterol in our arteries prompts a chronic, unresolving inflammatory response that damages our arteries and puts us at risk for heart attacks. What is interesting is that different people seem to respond in different ways to some of these inflammatory triggers. While treating risk factors like high cholesterol and high blood sugar alone is of course essential, many people still have harmful unresolving inflammation despite this, and these people have increased risk for heart and artery disease. 

There is still so much we don’t understand regarding the intersection between genes and environment, and how that makes some people especially prone to harmful, heart and artery-damaging inflammation. But bit by bit, modern tools enable us to understand the immune system and individual-level variation in ways unthinkable just one or two decades ago. I am optimistic that this will inform more precise, and potentially more effective, ways to treat inflammation and reduce the burden of heart and artery disease in humans. 

How is your research funded? 

Currently, it is funded by the National Heart, Lung, and Blood Institute via R01 project grants, as well as a recently funded American Heart Association (AHA) Strategically Focused Research Network grant. For the latter, we were selected at Northwestern as one of three AHA-funded centers nationally to study inflammation in cardiovascular disease. Each center has its own training program to fund postdoctoral scholars as well as three projects within it.   

Who inspires you? Who are your mentors? 

Many! The work to understand dynamic human immunology of cardiovascular disease requires thoughtful cross-disciplinary collaboration. I collaborate closely with Edward Thorp, a professor in the Department of Pathology who is an immunologist and scientist focused on fundamental mechanisms of how immunity and metabolism worsen, or can help resolve, cardiovascular diseases. This is an exciting synergy given my training as a clinical and translational scientist, with additional background in large-scale epidemiological study design. Collectively, this enables us to use causal approaches to answer human-relevant questions. Given growing interest in the role of inflammation in cardiovascular health and disease, as well as specific conditions such as rheumatologic conditions and HIV, marked by excess inflammation and cardiovascular risk, I also have close clinical and translational collaborators in other Divisions including Infectious Disease, Rheumatology, and Nephrology. I’d be remiss if I didn’t mention close collaborators in Cardiology and the Department of Preventive Medicine, given our shared interest in clinical and epidemiological approaches to understanding the role of inflammation in cardiovascular disease.   

I’m fortunate to name a number of folks as mentors and inspirations in various capacities. Donald Lloyd-Jones, MD, ScM, the Eileen M. Foell Professor of Preventive Medicine and a professor of Preventative Medicine and Pediatrics has been a key scientific, clinical and career mentor for me for more than 15 years since the summer between my first and second years of medical school. His excellence in all of these phases, as well as incredible ability to meet mentees where they’re at, is something I have and will always look up to. Neil Stone, MD, Robert Bonow, MD, Professor and professor of Preventative Medicine, has been a clinical mentor for me since medical school as well, demonstrating a rigorous and patient-centered focus on how to merge lifestyle- and medication-focused approaches to prevent and treat cardiovascular disease. I also find mentorship and inspiration from close colleagues, including Ed Thorp, given his focus and commitment to rigorously answering fundamental questions on immune mechanisms of cardiovascular disease, has been a clinical mentor for me since medical school as well, demonstrating a rigorous and patient-centered focus on how to merge lifestyle- and medication-focused approaches to prevent and treat cardiovascular disease. I also find mentorship and inspiration from close colleagues, including Edward Thorp, given his focus and commitment to rigorously answering fundamental questions on immune mechanisms of cardiovascular disease, Mercedes Carnethon, PhD, chair of the Department of Preventive Medicine and Mary Harris Thompson Professor, given her incredible clarity of thought and ability to efficiently distill complex scientific and career-related questions into their most important, actionable components, and Sanjiv Shah, MD, director of the Institute for Artificial Intelligence in Medicine, Center for Deep Phenotyping & Precision Therapeutics, and Neil J. Stone, MD, Professor, given his expertise in defining a clinical and scientific question of high importance and willingness to probe into that question to whatever depth necessary. I’m also continuously inspired by my trainees and mentees, both from a research and clinical standpoint, who have taken various paths to becoming the outstanding scientists and/or clinicians in training that they are. And, finally, my greatest inspiration on a daily/hourly basis is my wife, Carli, and two daughters, Levi and Sloane, who are more important to me than anything.