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Cholesterol attenuates linoleic acid-induced endothelial cell activation
Purushothaman Meerarani1, Eric J Smart, Michal Toborek
1Department of Animal Sciences, the Graduate Center for Nutritional Sciences, University of Kentucky, Lexington 40546-0215, USA.
Metabolism: Clinical and Experimental
|April 18, 2003
Summary
Cellular cholesterol levels protect vascular endothelial cells from linoleic acid-induced dysfunction by inhibiting inflammatory responses and altering signaling pathways. This finding is crucial for understanding atherosclerosis development.
Area of Science:
- Cardiovascular Biology
- Cellular Metabolism
- Atherosclerosis Research
Background:
- Vascular endothelial cell activation and dysfunction are key early events in atherosclerosis.
- Cholesterol, while implicated in cellular dysfunction at extreme levels, is vital for membrane integrity and may protect against oxidative stress and inflammation.
- Previous research indicated that linoleic acid activates vascular endothelial cells.
Purpose of the Study:
- To investigate the hypothesis that membrane cholesterol modifies and inhibits linoleic acid-mediated endothelial cell dysfunction.
- To explore the impact of cholesterol enrichment on linoleic acid-induced inflammatory responses in pulmonary artery endothelial cells.
Main Methods:
- Pulmonary artery endothelial cells were incubated with varying cholesterol concentrations (0-100 micromol/L) for 24 hours.
- Cells were subsequently treated with linoleic acid (90 micromol/L) for 6-24 hours.
- Assessed intracellular glutathione levels, nuclear factor-kappaB (NF-kappaB) DNA binding activity, interleukin-6 (IL-6) production, endothelial nitric oxide synthase (eNOS) activity, and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation.
Main Results:
- Linoleic acid reduced glutathione, increased NF-kappaB activity, upregulated IL-6, and altered eNOS activity.
- Cholesterol enrichment enhanced glutathione, reduced linoleic acid-induced NF-kappaB activation and IL-6 production.
- Cholesterol loading prevented fatty acid-induced eNOS activation and activated PPAR-gamma, which downregulated NF-kappaB.
Conclusions:
- Cellular cholesterol levels can modulate endothelial cell responses to linoleic acid, mitigating pro-inflammatory and pro-oxidant effects.
- Cholesterol-mediated activation of PPAR-gamma plays a role in suppressing linoleic acid-induced inflammation.
- These findings suggest that cellular cholesterol influences signaling pathways involved in endothelial cell activation by inflammatory stimuli.