NIH R01 · 2025
Role of hexokinase 3 in macrophage polarization and cardiac remodeling after myocardial infraction.
Project Summary Myocardial infarction (MI) is a leading cause of death, and macrophages play a critical role in the remodeling of the heart after MI. Hexokinases (HKs) catalyze glucose phosphorylation, and one HK isoform (HK3) is mostly expressed in myeloid cells. We have generated global and macrophage-specific (MS)-Hk3-/- mice and have shown that deletion of Hk3 leads to protection against cardiac ischemic injury and enhances polarization to the repair M2 subtype with unaltered M1/classical activation. Bone marrow derived macrophages (BMDMs) and circulating monocytes from mice with Hk3 deletion display increased glutathione levels and NRF2 activity; also, acute inactivation of HK3 leads…
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