Heart failure creates a lasting 'stress memory' in the body

Heart failure is a severe condition that leaves lasting effects on the body, leading to recurrent episodes and other health issues. Recent research has uncovered that it creates a “stress memory” in the body, marked by changes in DNA modifications of hematopoietic stem cells.

These stem cells are crucial for producing blood and immune cells, known as macrophages, which protect heart health.

However, during this condition, a vital signaling pathway called transforming growth factor beta (TGF-β) is suppressed in these stem cells, leading to dysfunctional macrophage production.

What is heart failure?

Heart failure occurs when the heart can’t pump blood efficiently, leading to insufficient blood flow to meet the body’s needs. Various conditions can cause heart failure, which often develops over a prolonged period.

Coronary artery disease is a primary cause, where plaque buildup narrows the arteries, reducing blood flow to the heart muscle. High blood pressure forces the heart to work harder, eventually weakening it. Heart attacks can damage the heart muscle, impairing its ability to pump.

Other causes include cardiomyopathy, where the heart muscle itself is damaged by factors like genetics, infections, or alcohol abuse. Valve diseases, where heart valves don’t function properly, can also contribute. Arrhythmias, or irregular heartbeats, can disrupt heart function. Chronic conditions like diabetes, obesity, and thyroid disorders increase the risk.

Infections, such as myocarditis, and lifestyle factors like smoking, poor diet, and lack of exercise further exacerbate the likelihood of heart failure. Effective management of these risk factors is crucial in preventing heart failure.

Stress memory of stem cells after heart failure

The United Nations’ global Sustainable Development Goals emphasize healthier lives and improved well-being.

A recent study projects an increase in global life expectancy by about 4.5 years by 2050, attributed to public health efforts and improved survival from illnesses, including cardiovascular disorders.

Despite these advances, heart disease remains the leading cause of death worldwide, affecting approximately 26 million people with heart failure – which is associated with a high risk of relapse.

Researchers at the University of Tokyo sought to understand the causes of heart failure recurrence, and whether it can be prevented.

“Based on our earlier research, we hypothesized that recurrence may be caused by stress experienced during heart failure accumulating in the body, particularly in hematopoietic stem cells,” explained Professor Katsuhito Fujiu.

Hematopoietic stem cells, located in bone marrow, are responsible for producing blood cells and macrophages, which are essential for heart health.

Stress imprinting on the epigenome

By studying mice, researchers discovered that stress imprints on the epigenome, causing chemical changes to their DNA. The suppression of the TGF-β signaling pathway in the hematopoietic stem cells of affected mice resulted in the production of dysfunctional immune cells.

This change persisted over time. When the researchers transplanted bone marrow from the affected mice into healthy ones, the stem cells continued to produce dysfunctional immune cells, leading to heart problems and organ damage in the healthy mice.

“We termed this phenomenon stress memory because the stress from heart failure is remembered for an extended period and continues to affect the entire body. Although various other types of stress might also imprint this stress memory, we believe that the stress induced by heart failure is particularly significant,” noted Professor Fujiu.

Preventing heart failure stress in stem cells

The identification and understanding of changes to the TGF-β signaling pathway open new possibilities for future treatments.

“Completely new therapies could be considered to prevent the accumulation of this stress memory during hospitalization for heart failure,” stated Professor Fujiu.

In animal studies, supplementing additional active TGF-β has shown potential as a treatment. Correcting the epigenome of hematopoietic stem cells might also help eliminate stress memory.

This research offers hope for developing innovative therapies to prevent the recurrence of heart failure and improve overall heart health.

By addressing the root cause of stress memory, new treatments could significantly enhance the quality of life for those affected by heart failure.

The study is published in the journal Science Immunology.

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