Linoleic acid atherosclerosis

McLeod, R.S., LeBlanc, A.M., Langille, M.A., Mitchell, P.L., Currie, D.L. 2004. Conjugated linoleic acids, atherosclerosis, and hepatic very-low-density lipoprotein metabolism. Am. J. Clin. Nutr. 79, 1169S-1174S. 

Toomey, S., Harhen, B., Roche, H. M., Fitzgerald, D., Belton, O. (2006). Profound resolution of early atherosclerosis with conjugated linoleic acid. Atherosclerosis, 187, 40-49. 

In relation to cancer, there is some evidence that highly oxidized and heated fats may have carcinogenic characteristics. HNE (4-hydroxy-2-frans-nonenal), a secondary lipid peroxidation product derived from linoleic acid oxidation, has assumed particular interest because it has shown cytotoxic and mutagenic properties. Its toxicity, as well other secondary lipid peroxidation products (HHE 4-hydroxy-2-frans-hexenal and HOE 4-h yd roxy-2-trans-oc ten al), is explained through the high reactivity with proteins, nucleic acids, DNA, and RNA. Research links them to different diseases such as atherosclerosis, Alzheimer s, and liver diseases (Seppanen and Csallany, 2006). Research is rapidly progressing, but results are still not conclusive. 

Kritchevsky, D., Tepper, S.A., Wright, S., Tso, P., Czarnecki, S.K. 2000. Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits.. / Am. Coll. Nutr. 19, 472S t77S. 

Munday, J.S., Thompson, K.G., James, K.A.C. 1999. Dietary conjugated linoleic acids promote fatty streak formation in the C57BL/6 mouse atherosclerosis model. Br. J. Nutr. 81,251-255. 

Nicolosi, R.J., Rogers, E.J., Kritchevsky, D., Scimeca, J.A., Huth, P.J. 1997. Dietary conjugated linoleic acid reduces plasma lipoproteins and early aortic atherosclerosis in hypercholester-olemic hamsters. Artery. 22, 266-277. 

Wilson, T.A., Nicolosi, R.J., Chrysam, M., Rritchevsky, D. 2000. Conjugated linoleic add reduces early aortic atherosclerosis greater than linoleic acid in hypercholesterolemic hamsters. Nutr. Res. 20, 1795-1805. 

Kritchevsky, D. 1999. Conjugated linoleic acid and experimental atherosclerosis in rabbits. In Advances in Conjugated Linoleic Acid Research, Vol. 1 (M.P. Yurawecz, M.M. Mossoba, J.K.G. Kramer, M.W. Pariza, G.J. Nelson, eds.), pp. 397 403, American Oil Chemists Society Press, Champaign, IL. 

Kritchevsky, D. 2003. Conjugated linoleic acid in experimental atherosclerosis. In Sebedio, J., Christie, W. W., and Adolf, R. (Eds.), Advances in Conjugated Linoleic Acid Research (2, pp. 292-301). Champaign, IL AOCS Press. 

Fatty acids with two or more conjugated double bonds are found in some plants and animals. In tissues of ruminant animals (and, hence, in meat and dairy products), fatty acids with conjugated diene system were detected as intermediates or by-products in the biohydrogenation of linoleic acid by microorganisms in the rumen. The main isomer, 9-cis, ll-fran -octadecadienoic acid, may account for up to 1% of the total fatty acids of milk fat. 9-cis, ll-fran5-15-cw-octadecatrienoic acid, derived from a-linolenic acid, is present in ruminant tissues only in trace levels. This fatty acid has been shown to have several medical properties, especially anti-cancer and anti-atherosclerosis effects. 

There, also, is interest in dietary monounsaturated fatty acids because of their possible protective effect against oxidation of LDL cholesterol (101). There is appreciable evidence that the uptake of LDL cholesterol and the formation of fatty streaks in the intima of large blood vessels, which is considered an early lesion of atherosclerosis, is enhanced by the oxidation of the LDL cholesterol (102, 103). LDL cholesterol was found to be appreciably more stable to oxidation when subjects were fed diets rich in oleic acid than when fed linoleic acid enriched diets (104-106). 

The oxidation of AA at C-15 is catalyzed by 15-LOXl, a soluble 661 amino acid-containing protein with a molecular weight of 74,673. Many cells express this enzyme that also efficiently oxidizes linoleic acid to 13-hydroperoxyoctadecadienoic acid and, to a lesser extent, 9-hydroperoxyoctadecadienoic acid because of broad substrate specificity to both 12-HpETE and 15-HpETE [31]. One distinguishing feature of 15-LOXl is that it can oxidize A A esterified to membrane phospholipids, thus forming esterified 15-HpETE. Expression of 15-LOXl is enhanced by several interleukins, suggesting a role of this enzyme in events such as atherosclerosis. 

Dietary intake of n-6 fatty acids such as linoleic acid, and n-3 fatty acids, such as the fish oils eicosapentanoic acid and docosahexaenoic acid, lowers plasma cholesterol and antagonizes platelet activation, but the fish oils are much more potent in this regard [26]. In particular, n-3 fatty acids competitively inhibit thromboxane synthesis in platelets but not prostacyclin synthesis in endothelial cells. These fatty acids have also been shown to have other potentially anti-atherogenic effects, such as inhibition of monocyte cytokine synthesis, smooth muscle cell proliferation, and monocyte adhesion to endothelial cells. While dietary intake of n-3 fatty acid-rich fish oils appears to be atheroprotective, human and animal dietary studies with the n-6 fatty acid linoleic acid have yielded conflicting results in terms of effects on both plasma lipoproteins and atherosclerosis. Indeed, excess amounts of both n-3 and n-6 fatty acids may actually promote oxidation, inflammation, and possibly atherogenesis (M. Toberek, 1998). In this context, enzymatic and non-enzymatic oxidation of linoleic acid in the sn-2 position of LDL phospholipids to 9- and 13-hydroxy derivatives is a key event in LDL oxidation (Section 6.2). 

Kurushima, H., Hayashi, K., Toyota, Y, Kambe, M., and Ka-jiyama, G. (1995) Comparison of Hypocholesterolemic Effects Induced by Dietary Linoleic Acid and Oleic Acid in Hamsters, Atherosclerosis 114, 213-221. 

It should not be assumed that hydroxy fatty acids are biologically inactive. Hydroxy fatty acids are chemotactic and vasoactive. Such fatty acids could perturb phospholipids in membranes. For instance, cardiolipin containing hydroxy-linoleic acid does not support the electron transport coupled to ATP production of the mitochondrion. 5-Hydroxy de-canoic acid is a well-known inhibitor of the K -ATP channel. Isoprostanes, trihydroxy oxidation products of arachi-donic acid, are vasoconstrictors (76). 13-Hydroxy linoleic acid (13-HODE) is a lipoxygenase-derived metabolite that influences the thromboresistant properties of endothelial cells in culture (77). However, there is some doubt about the tme nature of these hydroxy-fatty acids generated by the cells, as there are several GSH- and NADPH-dependent pathways that can immediately reduce hydroperoxy- to hydroxy-fatty acids. Furthermore, the reduction step of the analytical method would have converted the hydroperoxy- to a hydroxy-group. Nevertheless, much work remains to be done to determine the relative contribution of hydroperoxy- and hydroxy- to the biological effects of fried fat, and in particular their role in endothelial dysfunction and activation of factor VII. There have been earlier suggestions that a diet rich in lipid peroxidation products may lead to atherosclerosis and CHD (34,78). 

Conjugated Linoleic Acid Effects in Experimental Atherosclerosis... 

Necropsy Data For Rabbits with Established Atherosclerosis Fed Corn Oil with (Control) or Without 1% Conjugated Linoleic Acid (CLA) for 90 Days... 

Influence of Conjugated Linoleic Acid (CLA) Isomers and CLA Mix on Experimental Atherosclerosis in Rabbits ... 

---