Activation of the Unfolded Protein Response Occurs at All Stages of Atherosclerotic Lesion Development in Apolipoprotein E–Deficient Mice

• DOI: 10.1161/01.cir.0000160864.31351.c1
• Publication Date: 2005-04-05T00:30:59Z
• Authors: Ji Zhou; Šárka Lhoták; Brooke A. Hilditch; Richard C. Austin
• Keywords: Foam cell

Background— Apoptotic cell death contributes to atherosclerotic lesion instability, rupture, and thrombogenicity. Recent findings suggest that free cholesterol (FC) accumulation in macrophages induces endoplasmic reticulum (ER) stress/unfolded protein response (UPR) apoptotic death; however, it is not known at what stage of development the UPR induced or whether a correlation exists between activation, FC accumulation, death. Methods Results— Aortic root sections from apolipoprotein E–deficient (apoE −/− ) mice 9 weeks age (early-lesion group) 23 (advanced-lesion fed standard chow diet were examined for markers activation (GRP78, phospho-PERK, CHOP, TDAG51), (TUNEL cleaved caspase-3), lipid (filipin oil red O). dramatically increased very early intimal macrophage foam cells fatty streaks advanced lesions. Although was observed early-lesion–resident cells, no evidence observed; small percentage advanced-lesion–resident cells. Conclusions— occurs all stages development. The additional finding apoptosis did correlate with suggests other cellular mediators and/or pathways are required