PhD Scientific Days 2026

Poster Session 1.P - Cardiovascular Medicine and Research

The role of aging bone marrow in cardiac dysfunction in a mouse model of HFpEF

Name of the presenter

Alhaddad, Ayham

Institute/workplace of the presenter

Department of Pharmacology and Pharmacotherapy

Authors

Ayham R Alhaddad^1,2, Zsombor I Hegedűs^1,2, Lilla Szabó^1,2, Péter Ferdinandy^1,2, Zoltán V. Varga^1,2
1: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
2: Center for Pharmacology and Drug Research & Development, Semmelweis University, Budapest, Hungary

Text of the abstract

Background: Heart failure with preserved ejection fraction (HFpEF) continues to rise, particularly with aging. In addition to cardiac remodeling, fibrosis, and systemic inflammation, recent studies suggest an important role of the bone marrow-heart axis seen in HFpEF. However, the underlying mechanisms driving these changes, especially with aging, are still not well understood.
Purpose: We aim to investigate age-associated immunomodulatory and structural changes in the heart and bone marrow, providing insights into their roles in HFpEF disease progression.
Methods: Ten-week-old male C57Bl/6J mice were randomized to receive a control diet (CON) or a high-fat diet (HFD) + L-NAME for 17 weeks (n=10/group). Cardiac function was assessed by echocardiography. At termination, organs were collected for histological examination (Picrosirius Red, WGA, Isolectin B4), molecular analysis (qPCR), and RNA sequencing. To study the effect of aging, findings were compared with 17-month-old mice(n=8/group) subjected to the same protocol.
Results: Our echocardiographic results confirmed the development of the HFpEF phenotype in treated mice, characterized by preserved ejection fraction and signs of diastolic dysfunction (elevated E/E’ ratio), as well as Structural changes (LV wall thickening and increased LV mass). Histology revealed increased fibrosis, cardiomyocyte hypertrophy, and reduced microvascular density in the mice treated. Molecular and sequencing analyses of the heart revealed elevated inflammatory and fibrotic markers, along with cardiac remodeling, in the treated group. Importantly, aged mice exhibited more pronounced cardiac changes than young mice. Bone marrow studies using molecular and RNA sequencing revealed aging-driven inflammatory, fibrotic, and bone marrow remodeling, promoting stress hematopoiesis.
Conclusion: Our study successfully established an HFpEF mouse model characterized by fibrosis, hypertrophy, microvascular rarefaction, and inflammation. These changes were exacerbated by the aged bone marrow, emphasizing the potential role of age-related bone marrow dysfunction in heart failure. Moving forward, we aim to investigate specific inflammatory pathways linking bone marrow changes to the heart, providing novel therapeutic targets for the treatment of HFpEF.
Funding: Momentum Research Grant from the Hungarian Academy of Sciences (LP- 2021-38 to ZVV).