Project Grant R01HL181954

The National Heart, Lung, and Blood Institute awarded the Regents of the University of Michigan $724,971 on August 1, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to investigate macrophage 12-lipoxygenase signaling as a therapeutic target in heart failure with preserved ejection fraction (HFPEF).

The research program establishes 12-lipoxygenase (12-LOX), an enzyme that converts arachidonic acid into bioactive lipid mediators, as a master regulator of HFPEF progression by controlling macrophage inflammatory responses. The work combines macrophage-specific genetic deletion models with lipidomic profiling and immune phenotyping to determine the role of 12-LOX in macrophage polarization-mediated pathogenesis of HFPEF, identify molecular mechanisms by which 12-LOX-mediated macrophage polarization influences disease progression, and examine the therapeutic potential of novel 12-LOX inhibitors in attenuating HFPEF. Preliminary studies demonstrate that mice lacking 12-LOX or treated with systemic 12-LOX inhibition show markedly reduced cardiac dysfunction and inflammation when subjected to metabolic stress that typically induces HFPEF.

Performance occurs in Ann Arbor, Michigan. The award period runs from August 1, 2026, through April 30, 2030. This is a Project Grant, the standard assistance type for investigator-initiated research under NHLBI's portfolio.