Heart Failure Promotes Multimorbidity by Altering Stem Cells

New Insights from Science Immunology

A recent study published in Science Immunology reveals that heart failure (HF) not only significantly impacts the heart but also triggers multimorbidity by altering stem cells. Despite medical advances, HF continues to have a high mortality rate and often leads to repeated hospitalizations, suggesting an increased risk of future HF events and other related health issues. Chronic inflammation is a common pathological feature in many diseases associated with multimorbidity, but the specific role of HF in promoting chronic inflammation and multimorbidity has remained unclear.

Heart Failure’s Impact on Stem Cells and Health

The study, titled “Heart failure promotes multimorbidity through innate immune memory,” explored HF-induced changes in hematopoietic stem cells (HSCs) and their monocyte descendants, examining their effects on the heart, skeletal muscle, and kidneys. Researchers induced HF in mice by applying pressure overload through transverse aortic constriction (TAC) on the left ventricle. They then transplanted bone marrow (BM) from these HF mice into lethally irradiated mice. Four months later, the mice that received BM from HF mice exhibited increased fibrosis and decreased cardiac function compared to those that received BM from control mice.

Mechanisms of Multimorbidity

The study found that HSCs from TAC mice were more likely to develop into pro-inflammatory macrophages, leading to increased cardiac macrophages in BM recipients. This myeloid shift was also observed in peripheral blood cells derived from TAC BM. Additionally, TAC HSCs were found to promote renal injury and impaired muscle regeneration, indicating a broader impact on other organs.

Transcriptomic and Epigenomic Changes

Further analysis revealed that TAC altered gene expression and chromatin accessibility in HSCs, with significant downregulation of the transforming growth factor (TGF)-β signaling pathway. TGF-β signaling is crucial for HSC hibernation, and its reduction following TAC led to continuous HSC proliferation. Treating the HSCs with TGF-β1 suppressed this proliferation, suggesting that TGF-β signaling plays a key role in mediating the effects of cardiac stress on HSCs.

Conclusions

The study concludes that HSCs from HF mice not only lead to cardiac dysfunction but also increase the susceptibility of skeletal muscle and kidneys to further damage. The findings highlight that HF-induced HSC alterations drive inflammation and tissue remodeling, contributing to the development of multimorbidity. This research underscores the importance of understanding the broader impacts of HF on overall health and the potential for targeted therapies to mitigate these effects.

Meta Description: A study in Science Immunology reveals that heart failure promotes multimorbidity by altering hematopoietic stem cells, leading to inflammation and tissue damage in multiple organs.

Keywords: heart failure, multimorbidity, stem cells, Science Immunology, hematopoietic stem cells, chronic inflammation, cardiac function, renal injury, muscle regeneration, TGF-β signaling.