Atherosclerosis, Dyslipidemia, and Inflammation: The Significant Role of Polyunsaturated Fatty Acids

Abstract

Phospholipids play an essential role in cell membrane structure and function. The length and number of double bonds of fatty acids in membrane phospholipids are main determinants of fluidity, transport systems, activity of membrane-bound enzymes, and susceptibility to lipid peroxidation. The fatty acid profile of serum lipids, especially the phospholipids, reflects the fatty acid composition of cell membranes. Moreover, long-chain n-3 polyunsatured fatty acids decrease very-low-density lipoprotein assembly and secretion reducing triacylglycerol production. N-6 and n-3 polyunsatured fatty acids are the precursors of signalling molecules, termed “eicosanoids,” which play an important role in the regulation of inflammation. Eicosanoids derived from n-6 polyunsatured fatty acids have proinflammatory actions, while eicosanoids derived from n-3 polyunsatured fatty acids have anti-inflammatory ones. Previous studies showed that inflammation contributes to both the onset and progression of atherosclerosis: actually, atherosclerosis is predominantly a chronic low-grade inflammatory disease of the vessel wall. Several studies suggested the relationship between long-chain n-3 polyunsaturated fatty acids and inflammation, showing that fatty acids may decrease endothelial activation and affect eicosanoid metabolism.

Prostaglandin E3 metabolism and cancer

“…Upon incorporation into the membrane, AA and EPA can be released from cellular phospholipids by phospholipases following extracellular stimulation, while free DHA released from the membrane is undetectable [43]. Cytosolic free AA or EPA in cells can further be converted to downstream metabolites that differ both in the number of their double bonds for COX products (prostaglandins, PG) and lipoxygenase (LOX) products (HETEs and leukotrienes) and in their biological actions in a wide range of physiologic and pathologic processes [44], including inflammation and immunity [45], hemostasis [46,47], atherosclerosis [48,49] and cancer [50,51]. Further, the balance in tissues eicosanoids derived from AA and EPA is regulated by complex interactions/competitions between AA and EPA at multiple levels of the eicosanoid biosynthetic pathway [52].…”

Impact of a Standard Rodent Chow Diet on Tissue n‐6 Fatty Acids, Δ9‐Desaturation Index, and Plasmalogen Mass in Rats Fed for One Year

“…Fatty acids (FA), and particularly polyunsaturated fatty acids (PUFA), are bioactive lipids that display pleiotropic functions themselves [5,6] or as derivatives such as eicosanoids [7][8][9], docosanoids [10][11][12], linotrins [13], isoprostanes or phytoprostanes [14]. They can be either generated by de novo lipogenesis or supplied from food, so FA profiles reflect the balance between diet and biosynthesis potential, in predefined conditions of nutrition and physiology.…”

Dietary fat and cardiovascular disease?

“…This effect is associated with decreased inflammation and improved resistance to mitochondrial permeability transition. (6) Dietary guidelines must carefully consider the health effect of recommendations for alternative macronutrient to replace SF. (3) Saturated fat intake of around 20 g/day (approximately 10% of total energy) may be optimal, which corresponds to 200 g of milk a day and 150 g of meat every other day.…”