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Role of hepatokines in hypertension and cardiac dysfunction

Award Number: F31HL186795
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/21/2026
PERIOD OF PERFORMANCE END DATE: 12/20/2027

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Role of hepatokines in hypertension and cardiac dysfunction - The rates of metabolic dysfunction-associated steatotic liver disease (MASLD) have dramatically increased to 25% of the population in the U.S., reflecting the increase in obesity in the general population. Cardiovascular disease (CVD) is a significant complication of MASLD. More MASLD patients die from CVD than from liver disease. Many factors can contribute to the development of CVD in patients with MASLD as this condition is often associated with obesity, type II diabetes, and dyslipidemia. All of these factors can significantly contribute to the development of CVD. However, the contribution of hepatic steatosis to the development of CVD in MASLD is unknown. Our lab has developed a unique model to determine the role of hepatic steatosis in developing CVD independent of obesity and metabolic dysfunction, such as insulin resistance and dyslipidemia. We have exciting data showing that hepatocyte-specific deletion of peroxisome proliferator-activated receptor α (PparaHEPKO) results in significant hepatic steatosis even on mice maintained on a standard laboratory diet. PparaHEPKO mice develop hypertension, cardiac systolic and diastolic dysfunction, and increased vascular stiffness. This proposal will test the central hypothesis that MASLD suppresses liver-derived nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which promote healthy cardiovascular function. This proposal will use a combination of whole animal integrative physiology and molecular techniques to address the aims:Aim 1 will determine if increasing plasma NGF levels reverses hypertension and cardiovascular remodeling to improve cardiac function in PparaHEPKO mice. Aim 2 will determine whether increasing BDNF in the plasma of the PparaHEPKO mice reverses hypertension and cardiovascular remodeling to improve cardiac function in PparaHEPKO mice. This project will utilize state-of-the-art Pamgene kinome chip technology to determine which signaling mechanisms are impacted by increases in the plasma levels of these hepatokines. Our investigations will identify novel targets for the treatment of MASLD- derived CVD. This project is the first systematic investigation of the role of hepatic steatosis in the development of CVD in MASLD.


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 = $34,114 )
2026	2026	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Cardiovascular Diseases Research	000	1	6/25/2026	NEW	$34,114
														Subtotal = $34,114

Grand Total All Awards = $34,114

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Role of hepatokines in hypertension and cardiac dysfunction

Award Number: F31HL186795

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/21/2026

PERIOD OF PERFORMANCE END DATE: 12/20/2027

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