Abstract P052: Homocysteine Increases Macrophage-Derived Paraoxonase -1 Expression Independent of CD68 [Session Title: Poster Session 1- Trainee Onsite Poster Competition and Reception]

Although atherosclerotic plaque rupture is the leading cause of myocardial infarction, the mechanisms are unclear. Macrophages burdened with oxidized LDL (oxLDL) become foam cells: hallmarks of plaque progression and instability. One of the main macrophage-specific receptors for oxLDL is CD68. Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated lactonase capable of retarding/inhibiting LDL oxidation. Elevated levels of homocysteine (Hcy), an amino acid homologue and independent cardiovascular risk factor, is metabolized by Pon1.Given the literature connections of oxLDL, Pon1, Hcy, and macrophages to atherosclerosis, we hypothesized that Pon1 is produced by murine macrophages and its expression is increased by Hcy via CD68.Murine J774a.1 macrophages were treated with LDL, oxLDL, Hcy, or oxLDL+Hcy. Also, separate treatment groups included macrophages that had CD68 silenced by CD68 siRNA transfection. Cell lysates were analyzed for CD68 and Pon1 expression via Western blotting.Pon1 is present in macrophages. Hcy along with oxLDL significantly increases Pon1 (51%, 1.51 vs 0.97) expression compared to controls than oxLDL alone. Pon1 expression is significantly decreased (33%, 0.67 vs 1) with silencing of CD68. Pon1 expression is significantly decreased more with oxLDL (82% 0.17 vs 1) in presence of CD68 silencing but is significantly increased with oxLDL+Hcy (24% 1.24 vs 1). CD68 expression tends to increase more with oxLDL+Hcy than oxLDL alone when compared to con...
Source: Hypertension - Category: Cardiology Authors: Tags: Session Title: Poster Session 1- Trainee Onsite Poster Competition and Reception Source Type: research