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Experimental and interventional dietary study in humans on the role of HDL fatty acid composition in PGI 2 release and Cox‐2 expression by VSMC
Author(s) -
Escudero I.,
MartínezGonzález J.,
Alonso R.,
Mata P.,
Badimon L.
Publication year - 2003
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2003.01221.x
Subject(s) - arachidonic acid , polyunsaturated fatty acid , prostacyclin , medicine , docosahexaenoic acid , endocrinology , biochemistry , chemistry , protein kinase a , fatty acid , cyclooxygenase , kinase , biology , enzyme
Background High‐density lipoproteins (HDLs) induce prostacyclin (PGI 2 ) 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 PGI 2 synthesis in human VSMCs and to assess the impact that the intake of diets with different fatty acid composition exert on HDL‐induced PGI 2 release. Materials and methods Human VSMCs were treated with HDL or fatty acids in the presence or absence of different cell signalling inhibitors and PGI 2 (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 PGI 2 synthesis and Cox‐2 up‐regulation, while arachidonic acid (AA) but not other fatty acids mimicked the effects of HDL. Arachidonic acid induced PGI 2 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 PGI 2 release than that from the PUFA n‐6 period (64% vs. 100%). Conclusions Our results suggest that lipid moiety modulates HDL‐induced PGI 2 release/Cox‐2 up‐regulation in human VSMCs, and that changes in fatty acids as accomplished with the diet can modulate vascular PGI 2 homeostasis.