The endothelium can evoke relaxations of the underlying vascular smooth muscle, by releasing vasodilator substances. The best-characterized endothelium-derived relaxing factor (EDRF) is nitric oxide (NO) which activates soluble guanylyl cyclase in the vascular smooth muscle cells, with the production of cyclic guanosine monophosphate (cGMP) initiating relaxation. The endothelial cells also evoke hyperpolarization of the cell membrane of vascular smooth muscle (endothelium-dependent hyperpolarizations, EDH-mediated responses). As regards the latter, hydrogen peroxide (H2 O2 ) now appears to play a dominant role. Endothelium-dependent relaxations involve both pertussis toxin-sensitive Gi (e.g. responses to α2 -adrenergic agonists, serotonin, and thrombin) and pertussis toxin-insensitive Gq (e.g. adenosine diphosphate and bradykinin) coupling proteins. New stimulators (e.g. insulin, adiponectin) of the release of EDRFs have emerged. In recent years, evidence has also accumulated, confirming that the release of NO by the endothelial cell can chronically be upregulated (e.g. by oestrogens, exercise and dietary factors) and downregulated (e.g. oxidative stress, smoking, pollution and oxidized low-density lipoproteins) and that it is reduced with ageing and in the course of vascular disease (e.g. diabetes and hypertension). Arteries covered with regenerated endothelium (e.g. following angioplasty) selectively lose the pertussis toxin-sensitive pathway for NO release which favours vasospasm, thrombosis, penetration of macrophages, cellular growth and the inflammatory reaction leading to atherosclerosis. In addition to the release of NO (and EDH, in particular those due to H2 O2 ), endothelial cells also can evoke contraction of the underlying vascular smooth muscle cells by releasing endothelium-derived contracting factors. Recent evidence confirms that most endothelium-dependent acute increases in contractile force are due to the formation of vasoconstrictor prostanoids (endoperoxides and prostacyclin) which activate TP receptors of the vascular smooth muscle cells and that prostacyclin plays a key role in such responses. Endothelium-dependent contractions are exacerbated when the production of nitric oxide is impaired (e.g. by oxidative stress, ageing, spontaneous hypertension and diabetes). They contribute to the blunting of endothelium-dependent vasodilatations in aged subjects and essential hypertensive and diabetic patients. In addition, recent data confirm that the release of endothelin-1 can contribute to endothelial dysfunction and that the peptide appears to be an important contributor to vascular dysfunction. Finally, it has become clear that nitric oxide itself, under certain conditions (e.g. hypoxia), can cause biased activation of soluble guanylyl cyclase leading to the production of cyclic inosine monophosphate (cIMP) rather than cGMP and hence causes contraction rather than relaxation of the underlying vascular smooth muscle.

Endothelial dysfunction and vascular disease – a 30th anniversary update

Lipid oxidation analysis in food samples is a relevant topic since the compounds generated in the process are related to undesirable sensory and biological effects. Proper measurement of lipid oxidation remains a challenging task since the process is complex and depends on the type of lipid substrate, the oxidation agents and the environmental factors. A great variety of methodologies have been developed and implemented so far, for determining both primary and secondary oxidation products. Most common methods and classical procedures are described, including peroxide value, TBARS analysis and chromatography. Some other methodologies such as chemiluminescence, fluorescence emission, Raman spectroscopy, infrared spectroscopy or magnetic resonance provide interesting and promising results. Therefore, attention should be paid to these alternative techniques in the area of food lipid oxidation analysis.

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A review of analytical methods measuring lipid oxidation status in foods: a challenging task

Antioxidant system loss after slaughtering, reactive species production, cell disruption, contact with oxygen and light, heme and nonheme iron, and irradiation starts up mainly by 2 related oxidative processes: lipid peroxidation and protein oxidation. Products generated in these processes are responsible for meat quality loss, and some of them are suspected to be toxic to humans. This review article is focused on reactive species implicated in oxidative processes in meat, on lipid peroxidation mechanisms, heme protein, and nonheme protein oxidation, and on some toxic oxidation and digestion products. Nonenzymatic fatty acid peroxidation is exemplified by an arachidonic acyl group, and the initiation of chain reaction can be described by 3 pathways: singlet oxygen, hydroxyl radical from the Fenton reaction, and perferrylmyoglobin. Enzymatic oxidation of fatty acids is exemplified using linoleic acid, and the main characteristics of lipoxygenase are also presented. Heme protein oxidation is described in an interrelation with lipid peroxidation and the significance for food quality is shown. For protein oxidation, 3 different mechanism types are described: oxidation of amino acid residues, oxidation of protein backbone, and reactions of proteins with carbonyl compounds from lipid peroxidation. The effects of oxidative damage on protein properties and bioavailability are also shown. At the end of each oxidative process, the postprandial toxicity induced by oxidation products and the dietary degradation products are presented. Also discussed are reports by some researchers who suggest that dietary lipid and protein oxidation products and heme iron from red meat are in part cytotoxic and/or genotoxic.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/1541-4337.12241

Mechanisms of Oxidative Processes in Meat and Toxicity Induced by Postprandial Degradation Products: A Review.

Current and new insights on phytosterol oxides in plant sterol-enriched food.

Polymorphisms Associated With Cholesterol and Risk of Cardiovascular Events

Interaction of fatty acids with oxidation of cholesterol and β-sitosterol

Aims β-Sitosterol has become a popular cholesterol-lowering functional food product worldwide. β-Sitosterol can be oxidized to β-sitosterol oxidation products (SOPs) during food processing. Little is known about the impact of SOPs and β-sitosterol on the functionality of arteries. This study investigated the effects of SOPs and β-sitosterol on vasorelaxation and the possible cellular mechanisms involved.

Methods and results By isometric tension measurement, SOPs but not β-sitosterol blunted relaxation induced by acetylcholine or Ca2+ ionophore A23187 in endothelium-intact aortae. SOPs-impaired vasorelaxation was completely reversed by cyclooxygenase (COX)-2 inhibitor DuP-697, whereas the reversal by COX-1 inhibitor SC-560 was only partial. Western blotting and immunohistochemistry showed that SOPs increased the protein expression of COX-2 but not COX-1 in the endothelium. Using dihydroethidium staining and electron paramagnetic resonance spin trapping techniques, SOPs were found to elevate the level of reactive oxygen species in rat aortic endothelial cells, and the effects were reversed by antioxidants tempol, tiron, or diphenylene iodonium. Consistently, these antioxidants reversed SOPs-induced impairment of endothelium-dependent relaxation. Up-regulation of COX-2 expression by SOPs was also reversed by tempol. Moreover, SOPs attenuated nitric oxide donor sodium nitroprusside-induced relaxation in endothelium-intact, but not endothelium-denuded rings, confirming that SOPs act on the endothelium. Interestingly, a thromboxane-prostanoid (TP) receptor blocker S18886 reversed SOPs-impaired vasorelaxation, suggesting the involvement of TP receptor in mediating the downstream effect. SOPs decreased cGMP production, and the effect could be reversed by inhibiting COX-2 or TP receptor.

Conclusion This study provides novel experimental evidence showing the harmful effects of SOPs on endothelial function.

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Chao Yang

Papers

Interaction of fatty acids with oxidation of cholesterol and β-sitosterol

β-Sitosterol oxidation products attenuate vasorelaxation by increasing reactive oxygen species and cyclooxygenase-2.