Current Nutrition & Food Science - Volume 5, Issue 2, 2009

Leukocytes, platelets, and endothelial cells play a major role in atherosclerosis and coronary heart disease (CHD). Infiltration of intima by leukocytes and macrophages is one of the earliest events to occur in atherosclerosis, whereas leukocytosis is known to be associated with a greater cardiovascular risk. It is well documented that a close interaction occurs between platelets, leukocytes and endothelial cells. This cross talk among these three types of cells ultimately determines the initiation and progression of atherosclerosis and the occurrence of CHD. Under normal conditions, endothelial cells produce adequate amounts of prostaglandin E1 (PGE1), prostacyclin (PGI2), lipoxins (LXs), resolvins, and protectins from polyunsaturated fatty acids; and nitric oxide (NO) from L-arginine such that the proinflammatory and pro-atherosclerotic events induced by hemodynamic forces, hyperlipidemia, hypertension, smoking, hyperglycemia, hyperhomocysteinemia, and oxidant stress are abrogated. Pro-atherosclerotic and pro-inflammatory stimuli enhance the expression of nuclear factor-κB (NF-κB), VCAM-1, ICAM-1, PECAM, IL-1, IL-6, and MCP-1 in endothelial cells, leukocytes and platelets; and enhance the production of pro-inflammatory eicosanoids TXA2, PGE2, PGF2α, LTs, and other PGs, TXs, and LTs, free radicals (including myeloperoxidase) and UCP (uncoupling proteins) by endothelial cells, platelets, and leukocytes in atherosclerosis-susceptible regions that initiate and accelerate atherosclerosis. These events can be prevented and atherosclerosis process is arrested by the production of adequate amounts of PGE1, PGI2, PGI3, LXs, resolvins, protectins, NO, and anti-inflammatory cytokines such as IL-4, IL-10, TGF- β by endothelial cells, provided there are adequate stores of respective precursors of various PUFAs and L-arginine and their respective enzymes. This suggests that under physiological conditions a delicate balance is maintained between proand anti-inflammatory and pro and anti-atherosclerotic factors. When this delicate balance is tilted more towards proatherosclerotic and pro-inflammatory factors, atherosclerosis and CHD occurs.

Diabetic retinopathy and age-related macular degeneration (AMD) are due to neovascularization as a result of increased production of growth hormone, insulin-like growth factor (IGF), basic fibroblast growth factor (bFGF), transforming growth factor-β (TGF-ß), hepatocyte growth factor, placental growth factor, tumor necrosis factor-α (TNF- α) and vascular endothelial growth factor (VEGF) in response to hypoxia and ischemia of the inner retinal layers. Beneficial effects of recombinant humanized anti-VEGF antibody and demonstration of enhanced levels of VEGF in the plasma and vitreal fluid in diabetic retinopathy and AMD suggests that VEGF plays a central role in pathological retinal angiogenesis. Retinopathy of prematurity initiated by hyperoxia-induced obliteration of newly formed blood vessels in the retina as a consequence of hyperoxia-induced shut-off of VEGF production by neuroglial cells leads to selective apoptosis of endothelial cells. This premature apoptosis of endothelial cells leads to hypoxia of the developing retina that, in turn, leads to the production of abnormally high levels of VEGF and hence, anti-VEGF therapy is useful in the treatment of retinopathy of prematurity. Thus, AMD, diabetic retinopathy, and retinopathy of prematurity are all characterized by high levels of VEGF and neovascularization. Recent studies revealed that increased consumption of ω-3 polyunsaturated fatty acids (PUFAs) prevent or arrest the progress of retinal neovascularization. ω-and ω-6 PUFAs and their products lipoxins, resolvins and protectins have anti-inflammatory actions, suppress VEGF and tumor necrosis factor-α (TNF-α) production, and inhibit endothelial cell proliferation that may account for their beneficial effects in pathological retinal angiogenesis. These results emphasize the role of lipids in diabetic retinopathy, AMD and retinopathy seen in premature infants.

The essential PUFAs (polyunsaturated fatty acids) serve as precursors of several bioactive lipids molecules including the endocannabinoids (ECS). This article reviews the components of the endocannabinoid system, and their functions. Furthermore, a brief overview on the relationship of this system with some physiological and pathological processes, with focus on metabolic and mental disorders is discussed. Experimental and clinical effects of modification of the ECS and results of the exogenous manipulation of PUFAs and consequent modulation on ECS are also outlined. Finally, we propose that the ECS system can be favourably modulated by exogenous manipulation of PUFAs that could help in the prevention and management of several diseases.

Carcinogenesis involves a growing accumulation of genetic and epigenetic aberrations, leading to the deregulation of cellular homeostasis, followed by neoplastic progression. Although nutritional lipids play a critical role the specific transcriptional mechanisms involved in this process are not completely understood. In this review, we examine the biological effects of dietary essential fatty acids (n-3 and n-6 EFAs) and vitamin A, and the common pathways related to cancer chemoprevention. Eicosanoids (EFAs derivates) and retinoids (vitamin A derivates) are major mediators that act on their corresponding RXR-heterodimerized receptors (PPAR and RAR) and modify the carcinogenetic signalling pathways. Several effects of these mediators, mainly at DNA level, depend on specific molecular properties of the receptor isoforms and their differential affinities for their ligands, whose availability can be intentionally managed through diet. Nevertheless, the previous grade of differentiation in normal development or in cancer cells is an important modulatory factor of the cellular responses, especially when differentiating agents are evaluated. The potential of dietary EFAs and retinoids in chemoprevention and chemotherapy, through their actions on the cellular proliferation and differentiation processes, with particular reference to human breast cancer is discussed herein.

Multiple review articles have been published summarizing the evidence base for approaches to prevent childhood obesity. Literature reviews provide summaries of new knowledge from the empirical research as well as provide evidence for the state of the science. The purpose of this paper is to examine the state of the science of preventing childhood obesity by critiquing recently published review articles. We examine nine review articles published between 2000-2006 with stated purposes of reviewing primary prevention of childhood obesity. First, each review was examined for number of articles included, publication dates, inclusion/exclusion criteria, dependent variables, intervention channels and conclusions. Second, articles that were included in at least five of the reviews we describe study details and assess the articles for their scientific rigor. In general, the reviews indicated inconclusive evidence regarding effective youthcentered obesity prevention interventions, although several reviews offered ‘best practices’. Only nine articles, out of 152, were included in at least five reviews and only four of the nine articles met six of seven criteria for rigor. There is little evidence of effective youth-centered obesity prevention interventions and the state of the science is lacking in rigor.

Polyphenols constitute one of the most numerous and ubiquitous groups of plant metabolites and are an integral part of both human and animal diets. The main polyphenol dietary sources are fruit and beverages (wine, tea, coffee, chocolate and beer) and to a lesser extent vegetables, dry legumes and cereals. Dietary polyphenols are mostly derivatives and/or isomers of flavones, isoflavones, flavonols, catechins and phenolic acids, and possess various biological properties. Research on the effects of dietary polyphenols on human health has developed strongly and supports a role for polyphenols in the prevention of degenerative diseases, particularly cardiovascular diseases, anti-inflammation, antiatherosclerosis, cardiovascular protection, improvement of the endothelial function, as well as inhibition of angiogenesis and cell proliferation activity. This paper covers the elaborate literature on the subject, and highlights the functions and protective effects of dietary polyphenols.