A team of scientists led by Northwestern Medicine investigators have uncovered new details about a deadly heart condition with limited treatment options, according to a study published in the journal Circulation.
Heart failure with preserved ejection fraction, or HFpEF, occurs when the heart pumps normally but is too stiff to fill properly. Current research suggests that HFpEF occurs when chronic medical conditions damage the heart and other organ systems in the body.
The condition can be deadly and treatment options remain limited, said Mallory Filipp, PhD, a postdoctoral fellow and first author of the current study, who was a former student in the laboratory of Edward Benjamin Thorp, PhD, the Frederick Robert Zeit Professor of Pathology.
“We’ve known for years that inflammation plays an important role in this kind of heart failure,” Filipp said. “But the mechanisms and what exactly was happening was not well understood. So, we started by trying to figure out what immune cell subsets we could see within the heart.”
In the study, Filipp and her collaborators used flow cytometry and single-cell RNA sequencing to identify immune cell populations within human and animal models of HFpEF. Next, investigators observed immune cell activity in mice with HFpEF and high blood pressure that were fed a high-fat diet. They found that the mice had increased levels of blood stem cells and inflammatory proteins such as Vcam1, which has been linked to heart disease and inflammation.
Finally, by administering medications that reduce blood glucose in the mice, investigators found that levels of Vcam1 could be partially lowered.
Taken together, the findings offer new insights into the relationship between inflammation and heart disease, as well as offering a potential therapeutic target for HFpEF.
“The findings are a good reminder that the heart exists within this whole body that’s experiencing these systemic comorbidities,” Filipp said. “It’s not just about treating the heart individually, which is important, but treating the whole system: the whole patient.”
Building on these findings, Filipp and her colleagues will study HFpEF and inflammation further in human patients to better understand how the disease impacts immune system responses.
“Now we’re coming back full circle and asking, ‘Once these cells are in the heart, what are they doing that’s causing cardiac damage?’” Filipp said.
Filipp will continue her research in the laboratory of Sanjiv Shah, ’00 MD, the Neil J. Stone, MD, professor of Medicine in the Division of Cardiology.
The study was supported by National institutes of Health grants F31HL156408 and R35HL177401 and the American Heart Association project awards 24SFRNPCN1289611, 24SFRNPCN1291224 and 24SFRNCCN1276086.
