Macrophages lacking TSC2 have mTORC1-dependent increased GPNMB and ameliorate ventricular dysfunction/remodeling after ischemia-reperfusion.

ABSTRACT: Macrophages (MΦ) modulate myocardial inflammation and repair after ischemia-reperfusion (I/R) injury. The mechanistic target of rapamycin (mTOR) regulates MΦ phenotype and functionality, but studies conflict regarding its pro- or anti-inflammatory role. To test this, myeloid TSC2 depleted (MΦ^TSC2-/-) mice were generated by crossing Lys2^Cre with TSC2^flx/flx. In vitro, bone marrow-derived MΦ^TSC2-/- vs. control MΦ had greater mTORC1 and less mTORC2 activity coupled with differential responses to pro- or anti-inflammatory ligands. These disparities were eliminated by inhibiting mTORC1 with rapamycin. MΦ^TSC2-/- mice had substantially less cardiac dysfunction and ventricular remodeling after I/R, with reduced lung edema and activation of str

SUBMITTER: Keykhaei M 

PROVIDER: S-EPMC12630934 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature