Studying the role of inflammation in heart disease

• Link to: Northwestern Now Story

• Northwestern will focus on inflammation’s role in heart failure with preserved ejection fraction (HFpEF)
• HFpEF accounts for more than half of all heart failure cases in the U.S.
• Goal is to understand why some people experience unresolving inflammation while others do not

CHICAGO --- Northwestern Medicine scientists have been selected to lead one of only three research centers nationally as part of a $15 million American Heart Association (AHA) research initiative studying the role of inflammation in heart disease.

While inflammation is critical for mounting immune responses against pathogens or injuries, inflammatory dysregulation can fuel numerous diseases, including those in the heart.

“Fundamentally, we know that inflammation is an immune response to something, we understand the ‘something’ to a reasonable degree and we’re starting to understand the immune response better,” said Dr. Matthew Feinstein, associate professor of cardiology at Northwestern University Feinberg School of Medicine, who will direct one research center in the collaboration. “But there’s so much more work we need to do to understand the diversity of human immune responses that can lead some people to have inflammation go off the rails and some people to actually be able to resolve that inflammation and do it in a way that doesn’t lead to disease development.”

The four-year awards, funded by the AHA’s Strategically Focused Research Network (SFRN) on Inflammation in Cardiac and Neurovascular Disease, started April 1.

Partnering with Chicago State University, Northwestern’s research center will undertake three different projects focused on understanding inflammatory responses and how to treat heart disease caused by inflammation, specifically in patients with heart failure with preserved ejection fraction (HfpEF).

HfpEF is marked by excessive inflammation and accounts for more than half of all heart failure cases in the U.S. The condition also carries a significant public health burden: 50% of people diagnosed with HfpEF die within five years, according to the AHA.

Northwestern’s research initiatives will focus on immune cells, which regulate inflammation in the body, and how the cells are affected by stressors. Investigators will also analyze existing and novel approaches to modulating metabolism and immune cell responses in HfpEF with the ultimate goal of targeting inflammation to address the disease.

“We’ll do this by bringing together patient-centered approaches and experimental model systems, all coalescing around the question of ‘What is turning inflammation on and off in the setting of cardiometabolic risk factors and HfpEF?’” Feinstein said. “The goal is that this knowledge will inform approaches that modulate harmful, unresolving inflammation to curb cardiometabolic disease and HfpEF.”

The AHA funds SFRNs as part of its mission to advance cardiovascular health for all. Research teams apply for the program’s four-year grants with novel and innovative ideas to better understand cardiovascular diseases impacted by each research network’s focus, the latest of which is inflammation.

Other research teams selected as part of the network include investigators at the University of Pittsburgh, which will focus onidentifying and treating interrelated conditions of brain and vascular pathology; and University of Michigan, which will study the driving forces behind inflammatory processes linked to aging and obesity and how to prevent inflammation that could lead to heart failure, dementia and other diseases.

“Often times, the way we investigate inflammation in the heart and vascular disease can be really siloed,” Feinstein said. “We’re thrilled to start to break down some of these walls to understand fundamental features and mechanisms of cardiometabolic inflammation, and to do so in a patient-relevant way.”

Additional Feinberg faculty serving as principal investigators on projects in the Feinberg-based center include Dr. Sanjiv Shah, the Neil J. Stone, MD, professor of cardiology; Edward Thorp, the Frederick Robert Zeit Professor of Pathology; and Kiarri Kershaw, associate professor of preventive medicine (epidemiology).

Christopher Botanga, professor of biology and principal investigator at Chicago State University (CSU), will serve as director of training phase synergy. This collaboration will increase the pipeline of opportunities — which includes the NUCATS-supported Science Immersion Program — for CSU students to collaborate on specific projects as well as have near-peer mentoring from SFRN postdoctoral fellows. Obayed Raihan, assistant professor of pharmaceutical sciences at CSU, will help lead the project’s bioinformatics consortium, which will engage in shared methods development work on using bioinformatic approaches to understand immune-inflammatory contributors to cardiovascular disease.

“We are grateful to the AHA and excited for the opportunity to answer essential questions about how inflammation is regulated in cardiometabolic disease and HFpEF,” Feinstein said. “Ultimately, we hope that this knowledge will inform viable inflammation-modulating approaches to prevent and treat human disease.”