Arterial stiffening is a risk factor for cardiovascular disease, but how arteries stay supple is unknown. Here, we show that apolipoprotein E (apoE) and apoE-containing high-density lipoprotein (apoE-HDL) maintain arterial elasticity by suppressing the expression of extracellular matrix genes. ApoE interrupts a mechanically driven feed-forward loop that increases the expression of collagen-I, f...

A monoclonal antibody (YK-2), which was previously established to react with apolipoprotein E (apoE) peptides in systemic amyloid deposits, was further characterized. Epitope of this antibody was determined to be the residue 221 to 230 of apoE. In comparison with polyclonal anti-apoE antibodies, this antibody showed strong reactivity with apoE peptides in amyloid fibril preparation but poor rea...

Outcome of infection varies greatly among people, and in the case of three very different viruses, it is determined by apolipoprotein E (APOE) genotype. APOE might affect outcome of malaria infection also, since apoE protein and the protozoon (like the viruses) share cell entry mediators (heparan sulphate proteoglycans and/or specific apoE receptors). APOE polymorphisms give rise to protein var...

Expression of apolipoprotein E (apoE) and ciliary neurotrophic factor (CNTF), a pleiotropic neuron survival factor, increases in the CNS in response to injury. Although CNTF is believed to act as a survival factor after injury in the CNS, the functions of apoE in the CNS remain mainly unknown. Similarities between apoE and CNTF, including coinciding patterns of postinjury expression, extracellu...

AIMS Recent evidence suggests that both Ccr7 and its ligands, Ccl19 and Ccl21, are present in mouse and human atherosclerotic plaques; however, the role of Ccr7 in atherogenesis is still controversial. Here, we addressed this question by using the classic apolipoprotein E-deficient (ApoE(-/-)) mouse model of atherosclerosis. METHODS AND RESULTS Ccr7(-/-)ApoE(-/-) double knockout mice and Ccr7...

We have used two-dimensional polyacrylamide gel electrophoresis (PAGE) to study the plasma and hepatic apoE isoproteins of nonhuman primates and have compared them with their human counterparts. We have found that apoE obtained from fresh monkey or ape plasma, as well as nascent apoE synthesized by perfused monkey livers, is composed of several isoproteins that resemble the homozygous (beta) ap...

Under normal conditions, brain apolipoprotein E (apoE) is secreted and lipidated by astrocytes, then taken up by neurons via receptor mediated endocytosis. Free apoE is either degraded in intraneuronal lysosomal compartments or released. Here we identified a novel way by which apoE undergoes proteolysis in the extracellular space via a secreted neuronal protease. We show that apoE is cleaved in...

Recently, we showed expression of apolipoprotein E (apoE) in human neuronal-type cells such as neuroblastoma SK N SH-SY 5Y cells. In this model, a negative effect of neuronal differentiation on apoE synthesis was suspected. To check this hypothesis, we studied the regulation of apoE in human postmitotic neurons. The presence of apoE was investigated in undifferentiated human teratocarcinoma NT2...

Monoclonal antibody (Mab) 1D7 is specific for human apolipoprotein (apo) E and blocks binding of lipid-associated apoE to the low density lipoprotein (LDL) receptor. We report here that 1D7 can also block the binding of apoE-free LDL to the LDL receptor. The inhibition of LDL-receptor binding is not due to immunological cross-reactivity between the anti-apoE Mab and apoB, the ligand responsible...

Among extrahepatic tissues the adrenal gland has one of the highest concentrations of apoE mRNA and the highest rate of apoE synthesis. In the present investigation several previously described in vivo treatments were used to assess the relationship between apoE expression and cellular cholesterol in the rat adrenal gland. Treatment of rats with 4-aminopyrazolo[3,4-d]pyrimidine (4-APP) to lower...