Long-chain saturated fatty acids induce pro-inflammatory responses and impact endothelial cell growth.
OBJECTIVE
Saturated fatty acids (SFAs), significant components of enteral and parenteral formulations, have been linked to cardiovascular complications. However, the effect of SFAs upon vascular inflammation is less clear. Endothelial cells (EC) play an important role in the acute inflammatory responses. We, therefore, evaluated the acute effects of different chain-length SFAs upon EC functions.


METHODS
Endothelial cells were cultured with various SFAs. Growth and cytotoxicity were determined by WST-1 assay. Apoptosis and pro-inflammatory adhesion molecule (ICAM-1) expression was assayed using flow cytometry. Activation of NF-kappaB was analyzed using western blot analysis.


RESULTS
Long-chain SFAs (C14:0-C20:0) inhibited EC growth in a chain-length dependent manner. Medium-chain SFAs (C6:0-C12:0) did not significantly affect EC growth. In contrast, the short-chain SFA (C4:0) stimulated cellular growth. Stearic acid induced significantly more EC apoptosis and necrosis than palmitic acid or myristic acids. Stearic acid (>10muM) treatment also significantly increased ICAM-1 expression. Stearic acid's pro-inflammatory response was confirmed by phosphorylation of IkappaB-alpha and NF-kappaB in a dose dependent manner.


CONCLUSIONS
Long-chain SFAs can induce pro-inflammatory responses and significantly impact growth and viability of EC. Our data suggest that the presence of long-chain SFAs in parenteral formulations may have harmful effects on the vascular system.
Harvey
Kevin A
KA
Cellular Biochemistry Laboratory, Methodist Research Institute, Indianapolis, IN 46202, USA.
Walker
Candace L
CL
Pavlina
Thomas M
TM
Xu
Zhidong
Z
Zaloga
Gary P
GP
Siddiqui
Rafat A
RA
D017209:Apoptosis; D002318:Cardiovascular Diseases / Q000453:epidemiology; D002448:Cell Adhesion; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005227:Fatty Acids / Q000009:adverse effects* / Q000378:metabolism*; D005232:Fatty Acids, Volatile / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis; D009504:Neutrophils / Q000502:physiology; D009994:Osmolar Concentration; D010288:Parenteral Nutrition / Q000009:adverse effects; D010766:Phosphorylation; D013229:Stearic Acids / Q000009:adverse effects / Q000378:metabolism
D005227:Fatty Acids; D005232:Fatty Acids, Volatile; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D013229:Stearic Acids; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; C031183:stearic acid