Nutritional implications in vascular endothelial cell metabolism.

Abstract

Endothelial cells interact with blood components and the abluminal tissues, thus playing an active role in many aspects of vascular function. Numerous physiologic and pathophysiologic stimuli are often mediated by nutrients that can contribute to the overall functions of endothelial cells in the regulation of vascular tone, coagulation, cellular growth, immune and inflammatory responses. Therefore, nutrient-mediated functional changes of the endothelium and the underlying tissues may be significantly involved in disease processes such as atherosclerosis. There is evidence that individual nutrients or nutrient derivatives may either provoke or prevent metabolic and physiologic perturbations of the vascular endothelium. Diets high in fat and/or calories are considered a risk factor for the development of atherosclerosis. Our research has shown that certain diet-derived lipids and their derivatives can disrupt normal endothelial integrity, thus reducing the ability of the endothelium to act as a selectively permeable barrier to blood components. Mechanisms underlying fatty acid-mediated endothelial cell dysfunction may be related to changes in fatty acid composition as well as to an increase in cellular oxidative stress. Selective lipid accumulation and fatty acid changes in endothelial cells can modulate membrane fluidity, proteoglycan metabolism and signal transduction mechanisms. Most importantly, dietary fats rich in certain unsaturated fatty acids, may be atherogenic by enhancing the formation of reactive oxygen intermediates. A subsequent imbalance in cellular oxidative stress/antioxidant status can activate oxidative stress-responsive transcription factors, which in turn may promote cytokine production, expression of adhesion molecules on the surface of endothelial cells, and thus intensify an inflammatory response in atherosclerosis. Our data also suggest that certain nutrients, which have antioxidant and/or membrane stabilizing properties, can protect endothelial cells by interfering with lipid/cytokine-mediated endothelial cell dysfunction. These findings contribute to the understanding of the interactive role of dietary fats with inflammatory components, as well as with nutrients that exhibit antiatherogenic properties, in the development of atherosclerosis.

Activation of the AMP-Activated Protein Kinase by Eicosapentaenoic Acid (EPA, 20:5 n-3) Improves Endothelial Function In Vivo

“…In addition to activating eNOS, activated AMPK increases fatty acid oxidation by phosphorylating and inhibiting ACC, which serves to decrease the concentrations of malonyl-CoA [39]. Decreased malonyl-CoA could, in turn, inhibit the accumulation of lipids associated with endothelial dysfunction, which is the precursor of atherosclerosis [40]. Activation of AMPK also decreases fatty acid incorporation into glycerolipids, either secondary to its effect on fatty acid oxidation or through its ability to phosphorylate and inhibit sn-glycerophosphate acyltransferase, the first committed enzyme in diacylglycerol and triglyceride synthesis [41].…”

Triglyceride-rich lipoprotein lipolysis releases neutral and oxidized FFAs that induce endothelial cell inflammation

“…More specifically, atherosclerosis is correlated with postprandial hyperlipidemia, which is characterized by elevated TGRL levels in the blood, and there is increasing evidence that postprandial TGRLs are more atherogenic than fasting TGRLs (3,(29)(30)(31). TGRL lipolysis during the postprandial state releases excess FFAs in the immediate proximity of the endothelium, which may cause endothelial injury (11) and subsequent endothelial dysfunction (32). In addition, TGRL remnants derived from TGRL lipolysis are themselves atherogenic (33,34), Endothelial cell cultures in 12-well plates were treated for 2 h with individual lipids isolated from VLDL (50 mg/dl TG) with or without 30 min incubation with LpL (2 U/ml).…”

Endothelin in the female vasculature: a role in aging?

“…The vascular endothelium closely interacts and modulates functions of the underlying vascular smooth muscle cells (VSMC) and the extracellular matrix, thereby controlling vascular tone and diameter (which define peripheral resistance and, hence, the blood pressure). The endothelium also carries out important synthetic and metabolic functions and acts as a nonthrombogenic and selective permeable barrier under normal physiological conditions (40,84). Endothelial cell activation by stressful stimuli, such as proinflammatory cytokines and reactive oxygen species (ROS), may impair many endothelium-dependent vasoprotective functions, which precede the onset of symptomatic cardiovascular disease.…”