Experimental and interventional dietary study in humans on the role of HDL fatty acid composition in PGI2 release and Cox-2 expression by VSMC.
BACKGROUND
High-density lipoproteins (HDLs) induce prostacyclin (PGI2) release in vascular smooth muscle cells (VSMCs) by up-regulation of cyclooxygenase-2 (Cox-2). Our goal was to analyze the role of human HDL lipid moiety on Cox-2-dependent PGI2 synthesis in human VSMCs and to assess the impact that the intake of diets with different fatty acid composition exert on HDL-induced PGI2 release.


METHODS
Human VSMCs were treated with HDL or fatty acids in the presence or absence of different cell signalling inhibitors and PGI2 (by enzyme immunoassay) and Cox-2 protein levels (by Western blot) were analyzed. High-density lipoproteins were obtained from a plasma pool or from plasma of 12 volunteers subjected to a longitudinal dietary interventional study of three consecutive diets periods enriched in monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids n-6 (PUFA n-6) or n-3 (PUFA n-3).


RESULTS
High-density lipoprotein delipidation attenuated the effect of HDL on both PGI2 synthesis and Cox-2 up-regulation, while arachidonic acid (AA) but not other fatty acids mimicked the effects of HDL. Arachidonic acid induced PGI2 synthesis and Cox-2 expression through similar mechanisms to those activated by HDL [pertussis toxin-sensitive G proteins, p42/44 mitogen-activated protein kinase (MAPK), p38MAPK, and c-Jun N-terminal kinase-1 (JNK-1) pathways]. Finally, we observed that HDL from the PUFA n-3 dietary period induced lower PGI2 release than that from the PUFA n-6 period (64% vs. 100%).


CONCLUSIONS
Our results suggest that lipid moiety modulates HDL-induced PGI2 release/Cox-2 up-regulation in human VSMCs, and that changes in fatty acids as accomplished with the diet can modulate vascular PGI2 homeostasis.
Escudero
I
I
Centro de Investigación Cardiovascular, CSIC/ICCC-Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Martínez-González
J
J
Alonso
R
R
Mata
P
P
Badimon
L
L
D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D051546:Cyclooxygenase 2; D004032:Diet; D011464:Epoprostenol / Q000096:biosynthesis*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D007527:Isoenzymes / Q000032:analysis*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis*; D015398:Signal Transduction / Q000502:physiology
D005227:Fatty Acids; D007527:Isoenzymes; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D016718:Arachidonic Acid; D011464:Epoprostenol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases