Mice deficient in PKCβ and apolipoprotein E display decreased atherosclerosis

Endothelial activation is a central initiating event in atheroma formation. Evidence from our laboratory and others has demonstrated links between activation of early growth response-1 (Egr-1) and atherosclerosis and also has demonstrated that activated protein kinase C (PKC) βII is a critical upstream regulator of Egr-1 in response to vascular stress. We tested the role of PKCβ in regulating key events linked to atherosclerosis and show that the aortas of apoE−/− mice display an age-dependent increase in PKCβII antigen in membranous fractions vs. C57BL/6 animals with a ∼2-fold increase at age 6 wk and a ∼4.5-fold increase at age 24 wk. Consistent with important roles for PKCβ in atherosclerosis, a significant decrease in atherosclerotic lesion area was evident in PKCβ−/−/apoE−/− vs. apoE−/− mice by ∼5-fold, in parallel with significantly reduced vascular transcripts for Egr-1 and matrix metalloproteinase (MMP)-2 antigen and activity vs. apoE−/− mice. Significant reduction in atherosclerosis of ∼2-fold wa...