- Press Release Distribution

Understanding a broken heart

Recurrent heart failure linked to accumulated stress in immunity-forming stem cells

Understanding a broken heart
( The stress of heart failure is remembered by the body and appears to lead to recurrent failure, along with other related health issues, according to new research. Researchers have found that heart failure leaves a “stress memory” in the form of changes to the DNA modification of hematopoietic stem cells, which are involved in the production of blood and immune cells called macrophages. These immune cells play an important role in protecting heart health. However, a key signaling pathway (a chain of molecules which relays signals inside a cell), called transforming growth factor beta (TGF-β), in the hematopoietic stem cells was suppressed during heart failure, negatively affecting macrophage production. Improving TGF-β levels could be a new avenue for treating recurrent heart failure, while detecting accumulating stress memory could provide an early warning system before it occurs.

Healthier lives and improved well-being are among the United Nations’ global Sustainable Development Goals. Positively, a recent study shows that life expectancy worldwide is projected to increase by about 4.5 years by 2050. Much of this is thanks to public health efforts to prevent disease and improved survival from illnesses, such as cardiovascular disorders. However, heart disease is still the leading cause of death worldwide, with 26 million people estimated to be affected by heart failure. 

Once heart failure has occurred, it has a tendency to reoccur along with other health issues, such as kidney and muscle problems. Researchers in Japan wanted to understand what causes this recurrence and the deterioration of other organs, 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 Project Professor Katsuhito Fujiu from the Graduate School of Medicine at the University of Tokyo. Hematopoietic stem cells are found in bone marrow and are the source of blood cells and a type of immune cell called macrophages, which help to protect heart health.

By studying mice with heart failure, the researchers found evidence of stress imprinting on the epigenome, that is, chemical changes occurred to the mice’s DNA. An important signaling pathway, called the transforming growth factor beta, which is involved in regulating many cellular processes, was suppressed in the hematopoietic stem cells of mice with heart failure, leading to the production of dysfunctional immune cells. 

This change persisted over an extended period of time, so when the team transplanted bone marrow from mice with heart failure into healthy mice, they found that the stem cells continued to produce dysfunctional immune cells. The latter mice later developed heart failure and became prone to organ damage.

“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,” said Fujiu.

The good news is that by identifying and understanding these changes to the TGF-β signaling pathway, new avenues are now open for potential future treatments. “Completely new therapies could be considered to prevent the accumulation of this stress memory during hospitalization for heart failure,” said Fujiu. “In animals with heart failure, supplementing additional active TGF-β has been shown to be a potential treatment. Correcting the epigenome of hematopoietic stem cells could also be a way to deplete stress memory.” 

Now that it has been identified, the team hopes to develop a system that can detect and prevent the accumulation of stress memory in humans, with a long-term goal of being able to not only prevent the recurrence of heart failure, but also catch the condition before it can fully develop. DOI: 10.1126/sciimmunol.ade3814


Paper Title

Yukiteru Nakayama, Katsuhito Fujiu, Tsukasa Oshima, Jun Matsuda, Junichi Sugita, Takumi James Matsubara, Yuxiang Liu, Kohsaku Goto, Kunihiro Kani1, Ryoko Uchida, Norifumi Takeda, Hiroyuki Morita, Yingda Xiao, Michiko Hayashi, Yujin Maru, Eriko Hasumi, Toshiya Kojima, Soh Ishiguro, Yusuke Kijima, Nozomu Yachie, Satoshi Yamazaki, Ryo Yamamoto, Fujimi Kudo, Mio Nakanishi, Atsushi Iwama, Ryoji Fujiki, Atsushi Kaneda, Osamu Ohara, Ryozo Nagai, Ichiro Manabe, Issei Komuro. Heart failure promotes multimorbidity through innate immune memory. Science Immunology. 24 May 2024. 

Useful Links:

Graduate School of Medicine:  

The University of Tokyo Hospital:


This study was supported by the Grant-in-Aid for Scientific Research from JSPS, AMED, and JST (JP 18K08061, 21K08122, 21ek0210157h0001 to Y.N.; JP17H05594, JP17H04171, 17H04171, 19K22615, 20ek0109423h0001, 22gm6510010h0002, 23ek0210193h0001 to K.F.; JP19H03648, JP20H04938, JP20K21594, JP21gm5010002 to I.M.; JPMJMS2023 to K.F. and I.M.; and JP20gm0810013, JP20ek0109440, JP20ek0109487, JP20ek0109406, JP20km0405209, JP20ek021014, JP20ek0210118, JP20ek0109367, JP19bm0804010 to I.K.), and grants from the MSD Life Science Foundation International, Japan Foundation for Applied Enzymology, the Japan Cardiovascular Research Foundation (to Y. N.), and the Takeda Science Foundation and Uehara Memorial Foundation (to. I.M.).

Competing interests


Research Contact:

Project Professor Katsuhito Fujiu

Department of Advanced Cardiology

Graduate School of Medicine

The University of Tokyo, 7-3-1 Hongo

Bunkyo-ku, Tokyo, 113-8655, Japan

Tel.: +81-3-3815-5411


Press contact:
Mrs. Nicola Burghall (she/her)
Public Relations Group, The University of Tokyo,
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654, Japan

About the University of Tokyo

The University of Tokyo is Japan’s leading university and one of the world’s top research universities. The vast research output of some 6,000 researchers is published in the world’s top journals across the arts and sciences. Our vibrant student body of around 15,000 undergraduate and 15,000 graduate students includes over 4,000 international students. Find out more at or follow us on X at @UTokyo_News_en.


[Attachments] See images for this press release:
Understanding a broken heart Understanding a broken heart 2


Genetic cause of rare childhood immune disorders discovered

Scientists have pinpointed genetic changes that can leave children born with little to no immune defence against infection. In a new study of 11 affected individuals, researchers from Newcastle University, the Wellcome Sanger Institute, the Great North Children’s Hospital, and their collaborators were able to link mutations in the NUDCD3 gene to Severe Combined Immunodeficiency and Omenn syndrome1 – rare and life-threatening immunodeficiency disorders. These mutations prevented the normal development of diverse immune cells needed to combat different pathogens2. The findings, published today (24 May) in Science Immunology, ...

With wobbling stars, astronomers gauge mass of 126 exoplanets and find 15 new ones

With wobbling stars, astronomers gauge mass of 126 exoplanets and find 15 new ones
LAWRENCE — Using data from the Transiting Exoplanet Survey Satellite and W.M. Keck Observatory on Mauna Kea in Hawaii, an astronomer at the University of Kansas led a study appearing today revealing 15 new exoplanets — planets beyond our solar system — along with the mass of 126 other exoplanets. The findings give astronomers new understanding of the makeup of exoplanets and their star systems generally.  The study cataloging the exoplanets — comprising severe and exceptional environments, some of which hold promise to support life — was conducted under auspices of the TESS-Keck Survey and appears ...

High H5N1 influenza levels found in mice given raw milk from infected dairy cows

High H5N1 influenza levels found in mice given raw milk from infected dairy cows
WHAT: Mice administered raw milk samples from dairy cows infected with H5N1 influenza experienced high virus levels in their respiratory organs and lower virus levels in other vital organs, according to findings published in the New England Journal of Medicine. The results suggest that consumption of raw milk by animals poses a risk for H5N1 infection and raises questions about its potential risk in humans.  Since 2003, H5N1 influenza viruses have circulated in 23 countries, primarily affecting wild birds and poultry with about 900 human cases, primarily among people who have had close contact with infected birds. In ...

Study finds discreet shipping used to sell e-cigarettes to minors

Study finds discreet shipping used to sell e-cigarettes to minors
Researchers at the U of A found self-identified small business owners on TikTok are circumventing a number of local, state and federal laws that restrict the individual sale of tobacco products. Specifically, the researchers found that 45% of the videos highlighted the fact that they did not require identification to verify the purchaser’s age. “Many states have laws that govern procedures necessary to sell e-cigarettes,” explained lead researcher Page Dobbs, an associate professor of public health in the Department of Health, Human Performance and Recreation ...

African scientists call for equitable research partnerships to advance microbiome research

Leading African scientists have issued a compelling call for more equitable research partnerships in a new paper published in Nature Medicine. The paper underscores the critical need for fair and collaborative research efforts to explore the unique and diverse microbiomes found in African populations and environments. Historically, these microbiomes have been underrepresented in global studies. Over the past two decades, our understanding of the role played by the microbiome in different ecosystems has significantly expanded. For ...

How COVID-19 'breakthrough' infections alter your immune cells

How COVID-19 breakthrough infections alter your immune cells
LA JOLLA, CA—New research from scientists at La Jolla Institute for Immunology (LJI) suggests people who received COVID-19 vaccines and then experienced "breakthrough" infections are especially well armed against future SARS-CoV-2 infections. By analyzing blood samples from study volunteers, the LJI researchers discovered that people who experienced symptomatic breakthrough infections develop T cells that are better at recognizing and targeting SARS-CoV-2, including the Omicron and Delta variants. The researchers describe this increased protection as an "immunity wall." "The virus evolves, but, importantly, so does the immune system. T cells ...

Virginia Tech entomologist sheds light on 250-year-old mystery of the German cockroach

Virginia Tech entomologist sheds light on 250-year-old mystery of the German cockroach
May 24, 2024 -- A team of international scientists, including Virginia Tech entomologist Warren Booth, have solved the 250-year-old origin puzzle of the most prevalent indoor urban pest insect on the planet: the German cockroach. The team's research findings, representing the genomic analyses of over 280 specimens from 17 countries and six continents, show that this species evolved some 2,100 years ago from an outside species in Asia and were released this week in the Proceedings of the National Academy of Sciences journal.  One ...

Advancing skin science: explore Skin Ageing & Challenges 2024 Strategic Topics in Malta this November

Advancing skin science: explore Skin Ageing & Challenges 2024 Strategic Topics in Malta this November
Get introduced to the latest advances in skin research at the 15th International Conference on Skin Ageing & Challenges 2024 on November 5-6 at Corinthia Palace in Malta. Skin Ageing & Challenges 2024 will cover the hottest topics shaping the future of skin aging and rejuvenation. How will Skin Ageing & Challenges 2024 Expand Your Knowledge? Senolytics: Exploring new ways to fight cell aging with innovative senolytic treatments. Extracellular Vesicles: Discovering the potential of EVs for skin regeneration and repair. Skin Microbiota / Mitochondria Transplantation: Introducing approaches to harness the power of microbiome and mitochondrial transplantation ...

Controlling water, transforming greenhouse gases

Controlling water, transforming greenhouse gases
Carbon dioxide is the greenhouse gas, singlehandedly responsible for 78% of the change in energy balance in Earth's atmosphere between 1990 and 2022. A byproduct of burning fossil fuels, carbon dioxide enters the atmosphere from car exhaust and coal-fired power plants. Even some renewable energy resources produce a small amount of carbon dioxide, although at a tiny fraction of the amount coal and natural gas create. At its core, this molecule is just an arrangement of one carbon and two oxygen atoms that can be reorganized through a ...

MSK Research Highlights, May 24, 2024

MSK Research Highlights, May 24, 2024
New research from Memorial Sloan Kettering Cancer Center (MSK) investigates a promising approach against diabetic retinopathy and finds patients with early-onset colorectal cancer likely don’t need more frequent surveillance colonoscopies. Anti-ceramide immunotherapy promising against diabetic retinopathy, animal studies suggest Diabetic retinopathy is a condition that affects blood vessels in people with diabetes and can cause blindness. Now a new study from a team at MSK, Michigan State University, and the University of Oklahoma Health Sciences Center shows that diabetic retinopathy can be considered a “ceramidopathy” — which ...


Discovery of spontaneous inflow and outflow states of high-temperature plasma by energetic ions

Tax the rich, say a majority of adults across 17 G20 countries surveyed

Semaglutide leads to greater weight loss in women than men with HF, improves HF symptoms in both sexes

12.5, the 1st Impact Factor of COMMTR released!

Circadian clock impact on cluster headaches funded by $2.4M NIH grant for UTHealth Houston research

Study identifies first drug therapy for sleep apnea

How old is your bone marrow?

Boosting biodiversity without hurting local economies

ChatGPT is biased against resumes with credentials that imply a disability — but it can improve

Simple test for flu could improve diagnosis and surveillance

UT Health San Antonio researcher awarded five-year, $2.53 million NIH grant to study alcohol-assisted liver disease

Giving pre-med students hands-on clinical training

CAMH research suggests potential targets for prevention and early identification of psychotic disorders

Mapping the heart to prevent damage caused by a heart attack

Study challenges popular idea that Easter islanders committed ‘ecocide’

Chilling discovery: Study reveals evolution of human cold and menthol sensing protein, offering hope for future non-addictive pain therapies.

Elena Beccalli, new rector of Università Cattolica del Sacro Cuore, takes office on 1st July

Pacific Northwest Research Institute uncovers hidden DNA mechanisms of rare genetic diseases

Empowering older adults: Wearable tech made easier with personalized support

Pennington Biomedical researchers partner on award-winning Long Covid study

Cooling ‘blood oranges’ could make them even healthier – a bonus for consumers

Body image and overall health found important to the sexual health of older gay men, according to new studies

Lab-grown muscles reveal mysteries of rare muscle diseases

Primary hepatic angiosarcoma: Treatment options for a rare tumor

Research finds causal evidence tying cerebral small-vessel disease to Alzheimer’s, dementia

Navigating the Pyrocene: Recent Cell Press papers on managing fire risk

Restoring the Great Salt Lake would have environmental justice as well as ecological benefits

Cannabis, tobacco use, and COVID-19 outcomes

A 5:2 intermittent fasting meal replacement diet and glycemic control for adults with diabetes

Scientists document self-propelling oxygen decline in the oceans

[] Understanding a broken heart
Recurrent heart failure linked to accumulated stress in immunity-forming stem cells