Data on leukocyte PDZK1 deficiency affecting macrophage apoptosis but not monocyte recruitment, cell proliferation, macrophage abundance or ER stress in atherosclerotic plaques of LDLR deficient mice

Abstract

PDZK1 (Post-synaptic density protein/Drosophila disc-large protein/Zonula occludens protein containing 1) is an adaptor protein that binds to the HDL receptor, Scavenger receptor class B type I. Leukocyte PDZK1 deficiency in high fat-diet fed LDL receptor knockout mice has been found to increase atherosclerotic necrotic core formation and apoptosis of cells within atherosclerotic plaques. To explore mechanisms that may be involved, we examined the effects of leukocyte PDZK1 deficiency in mice on a number of processes that may impact macrophage abundance within atherosclerotic plaques. We found that leukocyte PDZK1 deficiency in high fat diet fed LDL receptor knockout mice did not affect the abundance of circulating red blood cells, myeloid cells or B- or T-lymphocytes. Leukocyte selective PDZK1 deficiency did not affect the levels of the ER chaperone proteins, detected with an antibody against the KDEL peptide, in macrophages or macrophage abundance, cellular proliferation or monocyte recruitment in atherosclerotic plaques. Leukocyte PDZK1 deficiency in otherwise wild type mice did result in increased sensitivity of macrophages to tunicamycin-induced apoptosis in a peritonitis model. HDL protected wild type macrophages from apoptosis induced by a variety of agents, including the ER stressor tunicamycin, oxidized LDL and exposure to UV irradiation. However, this protection afforded by HDL was lost when macrophages were deficient in PDZK1. HDL did not affect the level of ER stress induction by tunicamycin. Finally, PDZK1 deficiency in macrophages did not affect lipopolysaccharide-mediated induction of markers of M1 polarization. These data, utilizing mouse and cellular models, help to demonstrate that leukocyte PDZK1 plays a role in atherosclerosis by affecting macrophage apoptosis within atherosclerotic plaques.