scholarly journals Uptake of modified low-density lipoproteins alters actin distribution and locomotor forces in macrophages

2003 ◽  
Vol 284 (2) ◽  
pp. C555-C561 ◽  
Author(s):  
Celina V. Zerbinatti ◽  
Robert W. Gore
Keyword(s):  
Foam Cells ◽  
Force Transducer ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Force Frequency ◽  
Modified Low Density Lipoproteins ◽  
Generating Capacity ◽  
Induced Changes ◽  
Isometric Forces ◽  
Modified Forms

It is postulated that macrophage-derived foam cells accumulate in the arterial wall because they lose the ability to migrate after excessive ingestion of modified forms of low-density lipoproteins (LDL). To assess changes in locomotor force generating capacity of foam cells, we measured isometric forces in J774A.1 macrophages after cholesterol loading with oxidized (Ox-LDL) or aggregated (Agg-LDL) LDL using a novel magnetic force transducer. Ox-LDL loading reduced the ability of J774A.1 macrophages to generate isometric forces by 50% relative to control cells. Changes in force frequency consistent with reduced motility were detected as well. Agg-LDL loading was also detrimental to J774A.1 motility but to a lesser extent than Ox-LDL. Ox-LDL loading significantly reduced total actin levels and induced changes in the F-actin to G-actin distribution, whereas Agg-LDL loaded cells had significantly increased levels of total actin. These data provide evidence that cholesterol loading and subsequent accumulation decreases macrophage motility by reducing the cells' force generating capacity and that Ox-LDL appears to be more effective than Agg-LDL in disrupting the locomotor machinery.

Abstract 663: Modified Low Density Lipoproteins Elicited Macrophage InflammatoryResponses is Regulated by the Glycerolipid Synthesis Enzyme Lipin-1

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Aimee E Vozenilek ◽  
Aaron R Navratil ◽  
Jonette M Green ◽  
David Coleman ◽  
A. Wayne Orr ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Inflammatory Responses ◽  
Foam Cell ◽  
Foam Cells ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Wild Type ◽  
Modified Low Density Lipoproteins ◽  
Lipin 1 ◽  
Glycerolipid Synthesis

Modified low density lipoproteins (modLDL) elicit macrophage generation into foam cells that release pro-inflammatory mediators driving atherosclerotic lesion progression causing cardiovascular disease. The molecular mechanisms that elicit foam cell inflammatory responses have not yet been fully elucidated. The lipid-laden phenotype that is characteristic of macrophage foam cells is due to lipid droplet biogenesis in response to excess cholesterol. Lipid droplet biogenesis is a process that is thought to be symptomatic of, but not drive atherosclerosis. Lipid droplet biogenesis requires glycerolipid synthesis, during which, lipin-1 converts phosphatidate into diglyceride as the penultimate step of lipid droplet generation. We had previously demonstrated lipin-1 is also required for modLDL-elicited pro-inflammatory response from macrophages. We hypothesized that modLDL elicits chronic diglyceride generation, via lipin-1 enzymatic activity, that activates signaling cascades responsible for foam cell pro-inflammatory responses. To test our hypotheses we stimulated wild type and lipin-1 depleted bone marrow-derived macrophages (BMDMs) with oxidized LDLs (oxLDLs). Stimulation of wild type BMDMs resulted in chronic activation of the signaling kinases PKCα/βII, ERK1/2 and the AP-1 transcription factor subunit cJun (up to 48 hours after stimulation). This pathway was not observed to be active in BMDMs depleted of lipin-1 either genetically or with siRNA. The pharmacological inhibition of lipin-1, PKCα/βII, ERK1/2 strongly suggest lipin-1- PKCα/βII-ERK1/2-cJun represents a signaling axis. Finally, each of these proteins were required for oxLDL-elicited pro-inflammatory responses by macrophages. These results suggest that augmented glycerolipid synthesis in macrophages due to modLDL stimulation is not just symptomatic of atherosclerosis but promote inflammatory responses that drive lesion progression

Expression of receptors for native and chemically modified low-density lipoproteins in brain microvessels

FEBS Letters ◽  
1997 ◽  
Vol 401 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Marco Lucarelli ◽  
Massimo Gennarelli ◽  
Patrizia Cardelli ◽  
Giuseppe Novelli ◽  
Sigfrido Scarpa ◽  
...  
Keyword(s):  
Low Density Lipoproteins ◽  
Low Density ◽  
Chemically Modified ◽  
Brain Microvessels ◽  
Modified Low Density Lipoproteins

Effects of Modified Low-Density Lipoproteins on Human Retinal Pericyte Survival

2005 ◽  
Vol 1043 (1) ◽  
pp. 390-395 ◽  
Author(s):  
WEIWEI SONG ◽  
JEREMY L. BARTH ◽  
KANGMO LU ◽  
YONGXIN YU ◽  
YAN HUANG ◽  
...  
Keyword(s):  
Low Density Lipoproteins ◽  
Low Density ◽  
Modified Low Density Lipoproteins
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