Rapalogs Target the Endothelium to Set the Stage for Acute Lung Injury

Petrache and de Boer asserts that cellular signaling controlled by the serine/threonine kinase mTOR regulates, via the two complexes mTORC1 and mTORC2, fundamental cell functions such as organismal growth, proliferation, autophagy, aging, survival, and metabolism. It is therefore not surprising that mTOR inhibitors (mTORi) are increasingly used clinically, primarily as immunosuppressants and oncotherapeutics, for the management of multiple conditions, including lung transplantation and lymphangioleiomyomatosis. It is noteworthy that no phenotypic changes were noted in adult mice with haploid or conditional diploid depletion of endothelial Rptor or Rictor at baseline, whereas diploid loss of these genes in the endothelium during development is embryonically lethal. Although the subpotent efficiency of the target deletion (~50%) could explain these results, it is also possible that the effect of mTORi in the adult endothelium, during quiescent homeostatic conditions with low metabolic and repair demands, is better tolerated in mice.