Iron induces chronic heart failure in half of heart attack survivors, new study finds

Le fer induit une insuffisance cardiaque chronique chez la moitié des survivants d'une crise cardiaque, selon une étude historiqueNatureCommunications (2022). DOI: 10.1038/s41467-022-33776-x” width=”800″ height=”530″/>

A global model of how hemorrhagic infarction promotes chronic heart failure via fat deposition. a) After MI, compensatory remodeling promotes partial recovery of LV function in the first weeks after the index event. In hemorrhagic infarction, extravasated red blood cells promote active inflammation and participate in the formation of fatty deposits in the infarct area. This makes hemorrhagic MI very active with respect to functional losses, which define chronic heart failure (CHF). In contrast, non-hemorrhagic MI is not iron-rich and does not cause prolonged inflammation or promote fat deposition, which stabilizes the infarct area and leads to stable functional remodeling in the chronic phase. of the infarction. b) Iron is involved in a recurring cycle of events contributing to fat deposition in the chronic phase of hemorrhagic MI. Hemorrhagic iron promotes the recruitment of non-polarized macrophages and oxidizes lipids in its vicinity; the oxidized lipid and iron are taken up by macrophages which promote their polarization in a pro-inflammatory state and are transformed into foam cells. Foam cells produce ceroids and destabilize lysosomes and drive foam cell apoptosis, the remnants of which assist in fat deposition, with released iron being recycled back into the self-perpetuating pathway to continually support inflammation and growth fat deposition. Credit: Nature Communication (2022). DOI: 10.1038/s41467-022-33776-x

A multi-institution study led by Rohan Dharmakumar, Ph.D., of the Indiana University School of Medicine, identified that iron drives the formation of fatty tissue in the heart and leads to chronic heart failure in about 50% of heart attack survivors. The discovery, recently published in Nature Communicationpaves the way for treatments that could prevent heart failure in nearly half a million people a year in the United States and several million more around the world.

“For the first time, we have identified a root cause of chronic heart failure following a heart attack,” Dharmakumar said.

Dharmakumar is Executive Director of IU’s Krannert Cardiovascular Research Center and Associate Director of Research at the Cardiovascular Institute, a joint venture between IU School of Medicine and IU Health.

“While advancements in populations have made survival after heart attacks possible for most, too many survivors are suffering from long-term complications like heart failure,” said Subha Raman, MD, the institute’s chief medical officer. cardiovascular. “Dr. Dharmakumar’s breakthrough science sheds light on who is at risk and why and points to an effective way to prevent these complications.”

The study, which involved collaborators from institutions in the United States and Canada, followed large animal models for six months. He found that in heart attacks that lead to bleeding in the heart muscle – which accounts for about half of it – the scar tissue is slowly replaced by fat. Fat tissue cannot effectively flush blood from the heart, and this is what leads to heart failure and ultimately death in many survivors of hemorrhagic heart attacks, Dharmakumar said.

“Using non-invasive imaging, histology and molecular biology techniques, as well as various other technologies, we have shown that red blood cell iron is the driving force behind this process,” he explained. . “When we removed the iron, we reduced the amount of fat in the heart muscle. This finding paves the way for clinical investigations to remedy or ameliorate iron-associated effects in patients with hemorrhagic myocardial infarction.”

Dharmakumar’s team is currently testing iron chelation therapy to achieve this in a newly launched clinical trial.

“Thanks to an ongoing clinical trial led by his team at Indiana University, I am thrilled to see this treatment improving the lives of millions of heart attack survivors around the world,” Raman said.

More information:
Ivan Cokic et al, Intramyocardial hemorrhage leads to fatty degeneration of infarcted myocardium, Nature Communication (2022). DOI: 10.1038/s41467-022-33776-x

Provided by Indiana University School of Medicine

Quote: Iron induces chronic heart failure in half of heart attack survivors, new study finds (2022, November 1) retrieved November 2, 2022 from -chronic-heart-failure-survivors.html

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