Vascular wall: potential target for the physicochemical effects of cis-unsaturated free fatty acids

Diets rich in monounsaturated cis-FFA (cis FFA) are associated with a significant reduction of cardiovascular risk. Although several different mechanisms have been proposed to explain this protective effect, the biochemical processes involved have not been fully elucidated. It has been shown that upon their incorporation into the plasma membrane, cis FFA induce a marked perturbation of the lipid domains, altering membrane fluidity as well as lipid-lipid and lipid-protein interactions in the bilayer plane. During the last few years, several lines of evidence have shown that these perturbations disrupt the activity of several membrane proteins and enzymatic systems. As a result, several critical transmembrane signaling systems, including the Ins(1,4,5)P(3)/DAG/[Ca(2+)](i), the cAMP/PKA, and the voltage-operated Ca(2+) influx are strongly inhibited by cis FFA in different experimental models. Furthermore, this inhibition is associated with alterations in the timing of the cell cycle as well as in the final steps of the secretory pathway. We propose that this complex set of biological actions exerted by cis FFA at the plasma membrane may contribute to explain the protective roles that these molecules appear to exert on the vascular wall.