Universities collaborate on $15 million project investigating inflammation's role in cardiac and brain diseases

Research teams from Northwestern University Chicago Campus, University of Michigan and University of Pittsburgh will lead a $15 million project dedicated to studying inflammation's role in cardiac and brain diseases. The American Heart Association's Strategically Focused Research Network (SFRN) on Inflammation in Cardiac and Neurovascular Disease aims to better understand the body's response to inflammation and crosstalk between the heart and brain, as well as how to prevent or treat inflammation-driven cardiovascular diseases.

The American Heart Association, celebrating 100 years of lifesaving service as the world's leading nonprofit organization focused on heart and brain health for all, funds Strategically Focused Research Networks (SFRN) as part of its mission to be a relentless force for a world of longer, healthier lives. Research teams apply for the program's four-year grants with novel and innovative ideas to better understand cardiovascular diseases impacted by each SFRN focus, the latest of which is inflammation.

Inflammation is important for maintaining health of the body's tissues and for initiating a healthy immune response against pathogens or injury. However, when the inflammatory process goes awry, called inflammatory dysregulation, it can fuel development of diseases, including cardiovascular diseases.

Inflammation is a treatable risk factor for cardiovascular disease. The challenge is that there are gaps in knowledge about how to recognize and treat inflammation that could fuel heart and brain dysfunction. There are so many diseases linked to inflammatory dysregulation, including myocarditis, heart failure, heart attack, dementia and cognitive impairment, pulmonary vascular disease and others. People with numerous types of heart and brain diseases will benefit from this research."

Joseph C. Wu, M.D., Ph.D., FAHA, current volunteer president of the American Heart Association, director of the Stanford Cardiovascular Institute and the Simon H. Stertzer Professor of Medicine and Radiology at Stanford School of Medicine

The four-year awards, which started April 1, 2024, include a collaborative research project across all three groups. Additionally, to further the American Heart Association's commitments to expanding diversity in clinical research, each of the centers will work in conjunction with an academic institution that primarily serves individuals who are underrepresented in science. The research centers and the projects include:

• Northwestern University Chicago Campus – Led by center director Matthew J. Feinstein, M.D., M.Sc., FAHA, associate professor of medicine (cardiology) and director of the Clinical and Translational ImmunoCardiology Program at Northwestern's Bluhm Cardiovascular Institute, research teams at Northwestern University, collaborating with a team from Chicago State University, will undertake three different projects focused on inflammation in heart failure with preserved ejection fraction (HFpEF). This type of heart failure is marked by excess inflammation, accounts for more than half of heart failure cases in the U.S. and carries a significant public health burden: 50% of people diagnosed with HFpEF die within 5 years. Unfortunately, few treatments exist for HFpEF, and effective ways to target inflammation in HFpEF are limited. In these complementary projects, the researchers aim to determine how inflammation may be targeted at a cellular level to prevent and treat HFpEF. They will focus on immune cells, which crucially determine whether inflammation persists unchecked or resolves. Specifically, they will study ways that immune cells are primed by metabolic and other stressors to turn problematic inflammation on or off in various contexts, as well as how this impacts heart dysfunction and HFpEF. They will also investigate how existing and novel approaches targeting metabolism and immune cell function affect HFpEF onset and progression. The ultimate goal of these efforts is to develop specific, patient-relevant means of targeting inflammation to curb HFpEF.

• University of Michigan – Anthony Rosenzweig, M.D., FAHA, director of the Stanley and Judith Frankel Institute for Heart and Brain Health at Michigan Medicine, the academic medical center of the University of Michigan, will serve as the director of a collaborative research effort between Michigan Medicine and Massachusetts General Hospital. These research teams, in collaboration with a team from Oakland University in Rochester Hills, Michigan, 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. They will study mechanisms behind and potential treatments for cell senescence, a process that occurs with aging and unhealthy lifestyles that results in damaged cells. Inflammation from senescent cells can harm other cells, starting a cycle of inflammation that can damage the heart, brain and other organs. They are studying cells called microglia – the brain's main immune cells – and their counterpart, monocytes and macrophages, in the heart. The combination of aging with an unhealthy lifestyle can lead to dysfunction of these cells and inflammation in both the heart and the brain. These researchers want to understand this process better and learn how to prevent or lessen the inflammatory effects. They are expanding their research of a new investigational treatment that inhibits a pathway regulating metabolism and inflammation, as well as cardiac and skeletal muscle function. Early research suggests that the investigational treatment lessens inflammation, improves immune cell function and improves heart function. The proposal includes a first-ever clinical trial of this inhibitor for patients with unhealthy body weight and heart failure with preserved ejection fraction.

• University of Pittsburgh – Led by center director Stephen Y. Chan, M.D., Ph.D., FAHA, professor of medicine (cardiology) and director of the Vascular Medicine Institute, the University of Pittsburgh research teams, in collaboration with a team from Prairie View (Texas) A&M University, will conduct three different projects aimed at identifying and treating interrelated conditions of brain and vascular pathology. They will specifically look at how lysosomes, components of cells that contain digestive enzymes and dispose of excess or worn-out cell parts, control inflammation in blood vessel diseases like heart attacks and brain diseases like Alzheimer's disease. They will also work to develop new lysosomal medications by testing whether changes in a person's DNA and blood related to the lysosome can predict vascular disease and dementia and response to anti-inflammatory therapy. Additionally, these researchers will study cellular mechanisms that impact memory in hopes of developing new medications to boost brain function for people who have experienced a heart attack.

The American Heart Association has invested $278 million to establish 16 Strategically Focused Research Networks, each aimed at addressing a key strategic issue identified by the Association's volunteer Board of Directors. Networks have been studying prevention; hypertension; disparities in cardiovascular disease and stroke; women's health; heart failure; obesity; children; vascular disease; atrial fibrillation; arrhythmias/sudden cardiac death; cardiometabolic health/type 2 diabetes; health technology; cardio-oncology; diversity, diversity in clinical trials and the biological impact chronic psychosocial stress. Each network centers around the scientific knowledge and knowledge gaps, prevention, diagnosis and treatment of the key research topic. Three to six research centers make up each network, bringing together investigators with expertise in basic, clinical and population/behavioral health science to find new ways to diagnose, treat and prevent heart disease and stroke.

The American Heart Association has funded more than $5.7 billion in cardiovascular, cerebrovascular and brain health research since 1949, making it the single largest non-government supporter of heart and brain health research in the U.S. New knowledge resulting from this funding benefits lives worldwide.