Search

Fatty acid ethanolamides (NAEs) are naturally occurring hydrophobic molecules usually present in a very small amount in many mammalian tissues and cells. Moreover, these compounds have been isolated in mammalian biological fluids, such as blood. Palmitoylethanolamide (C16:0) (PEA) is a fully saturated NAE, which presents some possible pharmaceutical activities, such as anti-inflammatory and antinociceptive effects. PEA is physiologically present in the mammalian blood at concentrations ranging from 9.4 to 16.7 pmol/ml. Since increasing evidence indicates that oxidative modification of low-density lipoproteins (LDL) is an important determinant in atherogenesis, the aim of this study was to evaluate the effect of physiologically relevant concentrations of PEA on Cu2+-induced LDL oxidation (measured as conjugated dienes formation). Our experiments indicate both anti-oxidative and slightly pro-oxidative effects of PEA. The anti-oxidative effect is obtained at low PEA concentrations (0.01 and 0.1 microM), while the pro-oxidative effect is obtained at a higher PEA concentration (1 microM). Fluorescence and circular dichroism data indicate that the effect of PEA occurs mainly by affecting the conformational features of ApoB-100.

Binding of fibrinogen to platelets washed from the blood of patients with hypercholesterolemia and hypertriglyceridemia (n = 25) and control donors (n = 12) was compared. In addition, the content of platelet glycoprotein IIb was determined by radioimmunoassay. Fibrinogen was bound in significantly higher amounts (P < 0.02) to hyperlipidaemic platelets activated by ADP than to control ones (107,112 +/- 16,371 and 45,612 +/- 6495 molecules per platelet, respectively). The mean content of GPIIb was the same in hyperlipidaemic and in control platelets (2.06 +/- 0.16 and 1.94 +/- 0.21 micrograms/10(8) platelets, respectively). The amount of fibrinogen bound to the activated hyperlipidaemic platelets showed a positive correlation with total plasma cholesterol and LDL (r = 0.45 and 0.47, respectively) whereas a negative correlation with plasma HDL was found (r = -0.50). The increased expression of fibrinogen binding sites similar to that of hyperlipidaemic platelets could be produced by preincubation of normal platelets with palmitic acid. This was evidenced by a significant increase of fibrinogen binding sites in control platelets. This suggests that either palmitoylation of the receptor or microenvironment changes in the membrane lipid bilayer may be responsible for the enhanced platelet receptor capacity to bind fibrinogen.

The fatty acid composition of the cholesteryl esters in serum was measured in 7- and 8-year-old boys in groups from 16 countries. The ratio of esterified cholesterol: total cholesterol was also measured. All sample collections and analyses were carried out under standardized conditions. The proportion of palmitic acid in the cholesteryl esters was high in the groups from Asia and Africa (0.17-0.26) compared with that in the groups from the U.S.A. and Europe (0.14-0.18). The proportion of linoleic acid in the cholesteryl esters was low in the groups from Asia and Africa (0.39-0.48) and high in the groups from the U.S.A. and Europe (0.45-0.58). The proportion of oleic acid, arachidonic acid, palmitoleic acid and stearic acid showed little variation between the groups. The proportion of linoleic acid in the cholesteryl esters was positively correlated with the concentration of total cholesterol (r = 0.75, n = 26, P < 0.005).

The fatty acid patterns of serum triglycerides and FFA in SHR and in normotensive controls aged 4, 8 and 26 weeks were estimated by gas-liquid chromatography. In serum triglycerides of SHR, the percentage of linoleic acid (C18:2) was lower and the content of arachidonic acid (C20:4) higher than in age-matched control animals. A continuous increase in palmitic (C16) and linoleic acids as well as a decrease in arachidonic acid has been found with advancing age, the most striking differences existing between 4- and 8-week-old animals, i.e. before onset of arterial hypertension in SHR. In the pre-hypertensive stage, the percentage of arachidonic acid was about 3 times as high as in later stages in SHR. This gradation was, however, even more pronounced in normotensive control rats. The C18:2/C20:4-ratio of triglycerides was lower in SHR but increased with age in both groups reaching a 5--8-fold level. Similar behavior of the FFA fatty acid pattern was less marked. Alterations in levels of linoleic and arachidonic acids are of interest because of their pathogenic role as precursors of prostaglandins in the development of genetically spontaneous hypertension in rats. The results are discussed in connection with the hypotensive effect of a linoleic acid-rich diet recently reported in hypertensive rats.

Serum lipids and lipoproteins were investigated in 10 young quadriplegic patients. All received intermittently a liquid formula diet via a naso-gastric tube, consisting of 2900 calories/day. The polyunsaturated/saturated fatty acids ratio was 1.1 : 1. Their mean body weight was 70% of the ideal body weight. The results were compared to a control group receiving a diet containing 2600 calories per day, and the polyunsaturated/saturated fatty acids ratio was 0.9 : 1. Their mean body weight was 95% of the ideal body weight. In the quadriplegic group the serum HDL-cholesterol levels and linoleic acid content of cholesterol ester were reduced. Similar findings have been observed in patients with coronary disease.