Atherosclerosis is the major cause for chronic vascular diseases. The key event in the pathogenesis of atherosclerosis is believed to be dysfunction of the endothelium and disruption of endothelial homeostasis, leading to vasoconstriction, inflammation, leukocyte adhesion, thrombosis, and proliferation of vascular smooth muscle cells. Endothelium-derived nitric oxide (NO) plays a major role in vascular homeostasis and a decrease in NO-bioavailability accelerates the development of atherosclerosis. Given that endothelial dysfunction is at least in part reversible, the characterization of endothelial function and therapeutical approaches have gained much attention over the past years. Recent studies demonstrated that especially the consumption of plant-derived foods rich in certain flavonoids can improve endothelial function in both compromised and healthy humans. Furthermore, various physiologic and biochemical measures have been used previously as biomarkers for the assessment of the proposed beneficial effects of flavonoids in this context. More recently, the analysis of plasma nitros(yl)ated species (RXNOs), referred to as the circulating NO pool, has gained recognition, especially as a marker for endothelial function. This review is aimed at evaluating the suitability of quantifying this NO pool as a biomarker for cardiovascular function in humans, in particular during dietary interventions with flavonoid-rich foods.
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Fruits and vegetables have historically been considered rich sources of essential dietary micronutrients, soluble fiber, and antioxidants. More recently they are have been recognized as important sources for a wide array of phytochemicals that individually, or in combination, may benefit vascular health. Flavonoids are the largest, and most widely distributed class of phytochemicals, and can be further subdivided into several different sub-classes. Several epidemiology studies have observed an inverse association between flavonoid intake and risk of cardiovascular mortality. One sub-class of flavonoids, the flavanols, is found in foods such as grapes, red wine, tea, cocoa and chocolate; however, it is important to note that common food processing practices can significantly reduce the levels of these compounds found in finished food products. Recent studies have examined the potential of flavanol-rich cocoa and chocolates to influence vascular health. In this review, we discuss evidence for the hypothesis that the consumption of flavanol-rich cocoa can reduce the risk for cardiovascular disease through a multiplicity of mechanisms, including changes in oxidant defense mechanisms, vascular reactivity, cytokine production, and platelet function.
In the presence of a H(2)O(2)-generating system, myeloperoxidase (MPO) caused conjugated diene formation in low-density lipoprotein (LDL), indicating lipid peroxidation which was dependent on nitrite but not on chloride. The oxidation of LDL was inhibited by micromolar concentrations of flavonoids such as (-)-epicatechin, quercetin, rutin, taxifolin and luteolin, presumably via scavenging of the MPO-derived NO(2) radical. The flavonoids served as substrates of MPO leading to products with distinct absorbance spectra. The MPO-catalyzed oxidation of flavonoids was accelerated in the presence of nitrite.
Peroxynitrite is a mediator molecule in inflammation, and its biological properties are being studied extensively. Flavonoids, which are natural plant constituents, protect against peroxynitrite and thereby could play an anti-inflammatory role. Procyanidin oligomers of different sizes (monomer through nonamer), isolated from the seeds of Theobroma cacao, were recently examined for their ability to protect against peroxynitrite-dependent oxidation of dihydrorhodamine 123 and nitration of tyrosine and were found to be effective in attenuating these reactions. The tetramer was particularly efficient at protecting against oxidation and nitration reactions. Epicatechin oligomers found in cocoa powder and chocolate may be a potent dietary source for defense against peroxynitrite.
