Project Grant R01HL188752

The National Heart, Lung, and Blood Institute awarded the University of Texas Southwestern Medical Center $811,633 on September 1, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to investigate the role of endotrophin in heart failure with preserved ejection fraction.

The recipient will conduct basic and translational research examining endotrophin (ETP), a bioactive cleavage product of collagen VI, as a molecular driver of heart failure with preserved ejection fraction (HFPEF). Research aims include determining how ETP expression alters cardiac structure, function, and metabolism using gain-and-loss-of-function mouse models; identifying receptor pathways activated by ETP; and establishing whether ETP inhibition represents a viable disease-modifying therapy. Preliminary studies show ETP predicts incident HFPEF in humans, induces HFPEF-like cardiac dysfunction in mice, and activates SMAD signaling in cardiac fibroblasts. Neutralization of endogenous ETP with a humanized antibody improved diastolic function and reduced cardiac fibrosis in established mouse models, supporting therapeutic potential of targeting this pathway.

Work is performed in Dallas, Texas. The award period extends from September 1, 2026, through May 31, 2030. This is a Project Grant, the standard assistance type for investigator-initiated NIH research.