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Targeting Immune Cells to Save the Failing Heart

Award Number: F31HL186569
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/07/2027
PERIOD OF PERFORMANCE END DATE: 01/06/2028

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Targeting Immune Cells to Save the Failing Heart - Hypertension affects nearly 30% of adults globally and almost half of the adult population in the United States. Unfortunately, hypertension has no outward symptoms, leading to cardiac damage over the course of years or even decades. Due to the chronicity of this unrealized and uncontrolled cardiac insult, hypertension remains the leading cause of deadly cardiovascular disease worldwide. Cardiovascular disease can manifest in a number of different forms; however, heart failure remains one of the most common and deadly forms of the pathology. Frighteningly, nearly 13% of all deaths in the United States are attributed to heart failure, and the prevalence of the disease is projected to increase by 30% by 2030. Despite advancements in heart failure management, the fact remains that this is the end stage of a disease that has been progressing undetected for a great length of time. Indeed, nearly 60% of heart failure cases are caused by the silent killer: hypertension. As the prevalence of cardiovascular disease continues to rise, the focus in cardiovascular research has shifted to new ways to actively protect the heart during heart failure, rather than passive aid through the lowering of blood volume or vasodilation. In this regard, cells of the immune system have garnered much attention as both perpetrators of cardiac dysfunction and as valuable therapeutic targets. Despite these advances in the immunological treatment of heart failure, this is the end stage of a chronic disease that has steadily decreased cardiac function. In light of this fact, this proposal aims to investigate and understand the function of the immune system in the nascent stages of the pathology. In doing so, we intend to uncover the original immune antagonists in hypertension that set the stage for the irreversible devolution of cardiac health—focusing on the immune involvement of two crucial aspects of cardiovascular disease outlined in two specific aims. Aim 1) Is to investigate the role of T cell activation and accumulation in the hypertensive heart and subsequent cardiomyocyte dysfunction. Indeed, preliminary studies of the hypertensive heart revealed enhanced T-cell accumulation. Furthermore, in vitro, studies of T cell and cardiomyocyte interaction indicated direct adhesion of T cells to cardiomyocyte in culture, met with the generation of reactive oxygen species (ROS). This oxidative stress leads to calcium mishandling and dysfunction in the cardiac cycle. Aim 2) is to investigate the novel phenomenon of macrophage-to-myofibroblast transition (MMT) in the heart to determine its role in adverse fibrotic remodeling during hypertension. Excitingly, preliminary investigations show a significant increase in this MMT population in the heart, and primary in vitro studies have shed light on the molecular signals responsible for this differentiation. These studies will show that T cells and macrophages play a causal role in cardiac stress and remodeling during hypertension—essentially priming the heart for the end stages of this pathological continuum.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $40,754 )
2026	2026	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST	LITTLE ROCK	AR	72205	PULASKI	USA	Cardiovascular Diseases Research	000	1	7/9/2026	NEW	$40,754
														Subtotal = $40,754

Grand Total All Awards = $40,754

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Targeting Immune Cells to Save the Failing Heart

Award Number: F31HL186569

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/07/2027

PERIOD OF PERFORMANCE END DATE: 01/06/2028

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